CCL17 and CCL22 chemokines are upregulated in human obesity and play a role in vascular dysfunction.

Background/Aims: Chemokines are known to play critical roles mediating inflammation in many pathophysiological processes. The aim of this study was to investigate the role of chemokine receptor CCR4 and its ligands CCL17 and CCL22 in human morbid obesity. Methods: Circulating levels of CCL17 and CCL22 were measured in 60 morbidly obese patients (mean age, 45 ± 1 years; body mass index/BMI, 44 ± 1 kg/m2) who had undergone bariatric bypass surgery, and 20 control subjects. Paired subcutaneous (SCAT) and visceral adipose tissue (VCAT) from patients were analysed to measure expression of CCR4 and its ligands by RT-PCR, western blot and immunohistochemical analysis. The effects of CCR4 neutralization ex vivo on leukocyte-endothelial cells were also evaluated. Results: Compared with controls, morbidly obese patients presented higher circulating levels of CCL17 (p=0.029) and CCL22 (p<0.001) and this increase was positively correlated with BMI (p=0.013 and p=0.0016), and HOMA-IR Index (p=0.042 and p< 0.001). Upregulation of CCR4, CCL17 and CCL22 expression was detected in VCAT in comparison with SCAT (p<0.05). Using the parallel-plate flow chamber model, blockade of endothelial CCR4 function with the neutralizing antibody anti-CCR4 in morbidly obese patients significantly reduced leucocyte adhesiveness to dysfunctional endothelium, a key event in atherogenesis. Additionally, CCL17 and CCL22 increased activation of the ERK1/2 mitogen-activated protein kinase signalling pathway in human aortic endothelial cells, which was significantly reduced by CCR4 inhibition (p=0.016 and p<0.05). Conclusion: Based on these findings, pharmacological modulation of the CCR4 axis could represent a new therapeutic approach to prevent adipose tissue dysfunction in obesity.

Implicación de la isoforma antiangiogénica VEGF-A165b en la angiogénesis y la función sistólica tras un infarto de miocardio reperfundido / Role of antiangiogenic VEGF-A165b in angiogenesis and systolic function after reperfused myocardial infarction

Introducción y objetivos La angiogénesis participa en la restauración de la microcirculación después de un infarto agudo de miocardio (IAM). El objetivo de este estudio es explorar el papel que juega la isoforma anti-angiogénica del factor de crecimiento endotelial vascular (VEGF)-A165b y explorar su potencial como terapia coadyuvante a la reperfusión coronaria. Métodos Se realizaron dos modelos murinos de IAM: a) ligadura permanente de la arteria coronaria (IAM no reperfundido) y b) oclusión transitoria durante 45 minutos de la arteria coronaria seguida de reperfusión (IAM reperfundido); en ambos modelos, se realizó a los animales una ecocardiografía previa a la eutanasia el día 21 pos-IAM. Se determinaron los niveles séricos y miocárdicos de VEGF- A165b. En ambos modelos experimentales se evaluó la implicación funcional y estructural del bloqueo de esta isoforma. En una cohorte de 104 pacientes con IAM con elevación del segmento ST se cuantificaron los niveles circulantes de VEGF-A165b y se estudió su asociación con la fracción de eyección del ventrículo izquierdo determinada mediante resonancia magnética cardiaca a los 6 meses del IAM, así como con la aparición de eventos adversos (muerte, insuficiencia cardiaca o reinfarto) durante el seguimiento. Resultados En ambos modelos, los niveles séricos y tisulares de VEGF-A165b habían aumentado a los 21 días de la inducción del IAM. Además, existía una correlación negativa entre los valores circulantes de VEGF-A165b y la función sistólica evaluada mediante ecocardiografía. El bloqueo in vivo de VEGF-A165b se relacionó con una mayor densidad microvascular, menor tamaño de infarto y mejor fracción de eyección en el modelo de IAM reperfundido, pero no en el modelo de IAM no reperfundido. En la cohorte de pacientes, aquellos con unos niveles séricos elevados de VEGF-A165b presentaron una fracción de eyección deprimida y una mayor tasa de eventos adversos. Conclusiones ... (AU)

Introduction and objectives Angiogenesis helps to reestablish microcirculation after myocardial infarction (MI). In this study, we aimed to further understand the role of the antiangiogenic isoform vascular endothelial growth factor (VEGF)-A165b after MI and to explore its potential as a coadjuvant therapy to coronary reperfusion. Methods Two mice MI models were formed: a) permanent coronary ligation (nonreperfused MI); b) transient 45-minute coronary occlusion followed by reperfusion (reperfused MI); in both models, animals underwent echocardiography before euthanasia at day 21 after MI induction. We determined serum and myocardial VEGF-A165b levels. In both experimental MI models, we assessed the functional and structural role of VEGF-A165b blockade. In a cohort of 104 ST-segment elevation MI patients, circulating VEGF-A165b levels were correlated with cardiovascular magnetic resonance-derived left ventricular ejection fraction at 6 months and with the occurrence of adverse events (death, heart failure, and/or reinfarction). Results In both models, circulating and myocardial VEGF-A165b levels were increased 21 days after MI induction. Serum VEGF-A165b levels inversely correlated with systolic function evaluated by echocardiography. VEGF-A165b blockade increased capillary density, reduced infarct size, and enhanced left ventricular function in reperfused, but not in nonreperfused, MI experiments. In patients, higher VEGF-A165b levels correlated with depressed ejection fraction and worse outcomes. Conclusions In experimental and clinical studies, higher serum VEGF-A165b levels are associated with worse systolic function. Their blockade enhances neoangiogenesis, reduces infarct size, and increases ejection fraction in reperfused, but not in nonreperfused, MI experiments. Therefore, VEGF-A165b neutralization represents a potential coadjuvant therapy to coronary reperfusion. (AU)

Role of antiangiogenic VEGF-A165b in angiogenesis and systolic function after reperfused myocardial infarction.

INTRODUCTION AND OBJECTIVES: Angiogenesis helps to reestablish microcirculation after myocardial infarction (MI). In this study, we aimed to further understand the role of the antiangiogenic isoform vascular endothelial growth factor (VEGF)-A165b after MI and to explore its potential as a coadjuvant therapy to coronary reperfusion. METHODS: Two mice MI models were formed: a) permanent coronary ligation (nonreperfused MI); b) transient 45-minute coronary occlusion followed by reperfusion (reperfused MI); in both models, animals underwent echocardiography before euthanasia at day 21 after MI induction. We determined serum and myocardial VEGF-A165b levels. In both experimental MI models, we assessed the functional and structural role of VEGF-A165b blockade. In a cohort of 104 ST-segment elevation MI patients, circulating VEGF-A165b levels were correlated with cardiovascular magnetic resonance-derived left ventricular ejection fraction at 6 months and with the occurrence of adverse events (death, heart failure, and/or reinfarction). RESULTS: In both models, circulating and myocardial VEGF-A165b levels were increased 21 days after MI induction. Serum VEGF-A165b levels inversely correlated with systolic function evaluated by echocardiography. VEGF-A165b blockade increased capillary density, reduced infarct size, and enhanced left ventricular function in reperfused, but not in nonreperfused, MI experiments. In patients, higher VEGF-A165b levels correlated with depressed ejection fraction and worse outcomes. CONCLUSIONS: In experimental and clinical studies, higher serum VEGF-A165b levels are associated with worse systolic function. Their blockade enhances neoangiogenesis, reduces infarct size, and increases ejection fraction in reperfused, but not in nonreperfused, MI experiments. Therefore, VEGF-A165b neutralization represents a potential coadjuvant therapy to coronary reperfusion.

Modeling trade-offs across carbon sequestration, biodiversity conservation, and equity in the distribution of global REDD+ funds.

The program on Reducing Emissions from Deforestation and Forest Degradation (REDD+) is one of the major attempts to tackle climate change mitigation in developing countries. REDD+ seeks to provide result-based incentives to promote emission reductions and increase carbon sinks in forest land while promoting other cobenefits, such as the conservation of biodiversity. We model different scenarios of international REDD+ funds distribution toward potential recipient countries using 2 carbon emission reduction targets (20% and 50% compared to the baseline scenario, i.e., deforestation and forest degradation without REDD+) by 2030. The model combines the prioritization of environmental outcomes in terms of carbon sequestration and biodiversity conservation and social equity, accounting for the equitable distribution of international REDD+ funds. Results highlight the synergy between carbon sequestration and biodiversity conservation under alternative fund allocation criteria, especially for scenarios of low carbon emission reduction. Trade-offs increase when distributional equity is considered as an additional criterion, especially under higher equity requirements. The analysis helps to better understand the inherent trade-offs between enhancing distributional equity and meeting environmental targets under alternative REDD+ fund allocation options.

Disruption of the CCL1-CCR8 axis inhibits vascular Treg recruitment and function and promotes atherosclerosis in mice.

The CC chemokine 1 (CCL1, also called I-309 or TCA3) is a potent chemoattractant for leukocytes that plays an important role in inflammatory processes and diseases through binding to its receptor CCR8. Here, we investigated the role of the CCL1-CCR8 axis in atherosclerosis. We found increased expression of CCL1 in the aortas of atherosclerosis-prone fat-fed apolipoprotein E (Apoe)-null mice; moreover, in vitro flow chamber assays and in vivo intravital microscopy demonstrated an essential role for CCL1 in leukocyte recruitment. Mice doubly deficient for CCL1 and Apoe exhibited enhanced atherosclerosis in aorta, which was associated with reduced plasma levels of the anti-inflammatory interleukin 10, an increased splenocyte Th1/Th2 ratio, and a reduced regulatory T cell (Treg) content in aorta and spleen. Reduced Treg recruitment and aggravated atherosclerosis were also detected in the aortas of fat-fed low-density lipoprotein receptor-null mice treated with CCR8 blocking antibodies. These findings demonstrate that disruption of the CCL1-CCR8 axis promotes atherosclerosis by inhibiting interleukin 10 production and Treg recruitment and function.

Synthesis and biological evaluation of sphingosine kinase 2 inhibitors with anti-inflammatory activity.

The synthesis of inhibitors of SphK2 with novel structural scaffolds is reported. These compounds were designed from a molecular modeling study, in which the molecular interactions stabilizing the different complexes were taken into account. Particularly interesting is that 7-bromo-2-(2-phenylethyl)-2,3,4,5-tetrahydro-1,4-epoxynaphtho[1,2-b]azepine, which is a selective inhibitor of SphK2, does not exert any cytotoxic effects and has a potent anti-inflammatory effect. It was found to inhibit mononuclear cell adhesion to the dysfunctional endothelium with minimal impact on neutrophil-endothelial cell interactions. The information obtained from our theoretical and experimental study can be useful in the search for inhibitors of SphK2 that play a prominent role in different diseases, especially in inflammatory and cardiovascular disorders.

Intravital Microscopy in the Cremaster Muscle Microcirculation for Endothelial Dysfunction Studies.

The intravital microscopy in the mouse cremaster muscle microcirculation is a method widely used to visualize in vivo blood cells interacting with the endothelium and within the vessels. Therefore, it is a suitable technique to study leukocyte-endothelial cell interactions along every stage of the canonical leukocyte recruitment cascade: rolling, adhesion, intravascular crawling, and migration both in postcapillary venules and arterioles of the mouse cremasteric microcirculation. This technique also enables to assess vessel functionality, since hemodynamic parameters such as shear stress, flow rate, and vasodilatation/vasoconstriction, among other vascular events, can be additionally determined. Furthermore, response to multiple drugs and mechanisms underlying blood cells interactions within the vascular system can be studied in a real scenario. This chapter describes a protocol for intravital microscopy in the mouse cremaster muscle microcirculation.

Consenso del GEITDAH sobre los trastornos de conducta en niños y adolescentes / GEITDAH consensus on conduct disorders in children and adolescents

El Grupo de Especial Interés en el Trastorno por Déficit de Atención/Hiperactividad (GEITDAH) presenta en este artículo un consenso de expertos de toda España sobre los trastornos de conducta en niños y adolescentes. A partir del trabajo inicial del equipo de la Unidad de Paidopsiquiatría del Hospital Quirón-Teknon de Barcelona, se han consensuado aspectos básicos que podrían ser el punto de partida para futuros consensos. Ha sido también objetivo prioritario del trabajo actualizar en los trastornos de conducta en niños y adolescentes los criterios del Manual diagnóstico y estadístico de los trastornos mentales, quinta edición, y su comorbilidad con el trastorno por déficit de atención/hiperactividad (AU)

In this paper, the Special Interest Group on Attention Deficit Hyperactivity Disorder (GEITDAH, from its name in Spanish) presents a consensus reached by experts from all over Spain on conduct disorders in children and adolescents. Following the initial work by the team at the Pedopsychiatry Unit at the Quirón-Teknon Hospital in Barcelona, agreements have been reached on a number of basic aspects that could be the starting point for future consensuses. A top priority aim of the work was also to update the criteria in the Diagnostic and statistical manual of mental disorders, fifth edition, for conduct disorders in children and adolescents, together with their comorbidity with attention deficit hyperactivity disorder (AU)

[GEITDAH consensus on conduct disorders in children and adolescents]. / Consenso del GEITDAH sobre los trastornos de conducta en niños y adolescentes.

In this paper, the Special Interest Group on Attention Deficit Hyperactivity Disorder (GEITDAH, from its name in Spanish) presents a consensus reached by experts from all over Spain on conduct disorders in children and adolescents. Following the initial work by the team at the Pedopsychiatry Unit at the Quiron-Teknon Hospital in Barcelona, agreements have been reached on a number of basic aspects that could be the starting point for future consensuses. A top priority aim of the work was also to update the criteria in the Diagnostic and statistical manual of mental disorders, fifth edition, for conduct disorders in children and adolescents, together with their comorbidity with attention deficit hyperactivity disorder.

TITLE: Consenso del GEITDAH sobre los trastornos de conducta en niños y adolescentes.El Grupo de Especial Interes en el Trastorno por Deficit de Atencion/Hiperactividad (GEITDAH) presenta en este articulo un consenso de expertos de toda España sobre los trastornos de conducta en niños y adolescentes. A partir del trabajo inicial del equipo de la Unidad de Paidopsiquiatria del Hospital Quiron-Teknon de Barcelona, se han consensuado aspectos basicos que podrian ser el punto de partida para futuros consensos. Ha sido tambien objetivo prioritario del trabajo actualizar en los trastornos de conducta en niños y adolescentes los criterios del Manual diagnostico y estadistico de los trastornos mentales, quinta edicion, y su comorbilidad con el trastorno por deficit de atencion/hiperactividad.

Recomendaciones del GEITDAH en el tratamiento nutricional del déficit de atención con y sin hiperactividad (TDAH) / Recommendations on the nutritional treatment of attention deficit hyperactivity disorder (ADHD)

El grupo GEITDAH (Grupo de Especial Interés en el Trastorno por Déficit de Atención/Hiperactividad) presenta en este artículo un consenso de expertos de toda España sobre el tratamiento nutricional del TDAH. El tratamiento del trastorno por déficit de atención con o sin hiperactividad (TDAH) debe ser multimodal. El tratamiento nutricional es suplementario y comienza a haber pruebas científicas de su eficacia. Las intervenciones dietéticas pueden tener pequeños efectos beneficiosos en los síntomas del TDAH. La controvertida eliminación de aditivos artificiales, conservantes, colorantes y azúcares ha sido bien estudiada, y no tiene suficiente soporte científico por el momento para su recomendación generalizada como tratamiento eficaz del TDAH. Tampoco el empleo adicional de Acetil-L Carnitina con metilfenidato. Los suplementos de hierro o zinc deben suministrarse en los pacientes con TDAH con deficiencias conocidas. En este momento los hallazgos de los ensayos controlados aleatorizados son demasiado limitados y no apoyan de forma definitiva hasta la fecha el uso habitual en la práctica clínica de los ácidos grasos esenciales (omega-3 y 6) como tratamiento primario o suplementario en los niños con TDAH. Aunque, parecen aliviar síntomas relacionados con el TDAH, al menos en algunos niños, y los beneficios son mayores en el colegio que en casa

In this article, the GEITDAH -the Spanish abbreviation of the Special Interest Group on Attention Deficit Hyper-activity Disorder (ADHD)- presents a consensus about nutritional treatment for ADHD reached by experts in the management of ADHD from all over Spain. The ADHD treatment should be multimodal.Nutritional treatment is supplementary and there is some begining evidence of modest efficacy. Dietary interventions can have little beneficial effects in ADHD symptomatology. The controversial restricted elimination of food additives, preservatives, artificial food colours and refined sugar from diet is good studied. Present findings do not support to date the positive recommendation of its use as an appropriate treatment in ADHD. Neither do they support Acetyl-L Carnitine supplementation to augment methylphenidate. Iron and zinc should be supplemented in selected patients with know deficiencies. Current findings from randomized trials are limited and have not consistently supported the generalized clinical use of PUFA supplements (omega-3 fatty acids) as a primary or supplementary treatment for children with ADHD

Novel applications of motif-directed profiling to identify disease resistance genes in plants.

BACKGROUND: Molecular profiling of gene families is a versatile tool to study diversity between individual genomes in sexual crosses and germplasm. Nucleotide binding site (NBS) profiling, in particular, targets conserved nucleotide binding site-encoding sequences of resistance gene analogs (RGAs), and is widely used to identify molecular markers for disease resistance (R) genes. RESULTS: In this study, we used NBS profiling to identify genome-wide locations of RGA clusters in the genome of potato clone RH. Positions of RGAs in the potato RH and DM genomes that were generated using profiling and genome sequencing, respectively, were compared. Largely overlapping results, but also interesting discrepancies, were found. Due to the clustering of RGAs, several parts of the genome are overexposed while others remain underexposed using NBS profiling. It is shown how the profiling of other gene families, i.e. protein kinases and different protein domain-coding sequences (i.e., TIR), can be used to achieve a better marker distribution. The power of profiling techniques is further illustrated using RGA cluster-directed profiling in a population of Solanum berthaultii. Multiple different paralogous RGAs within the Rpi-ber cluster could be genetically distinguished. Finally, an adaptation of the profiling protocol was made that allowed the parallel sequencing of profiling fragments using next generation sequencing. The types of RGAs that were tagged in this next-generation profiling approach largely overlapped with classical gel-based profiling. As a potential application of next-generation profiling, we showed how the R gene family associated with late blight resistance in the SH*RH population could be identified using a bulked segregant approach. CONCLUSIONS: In this study, we provide a comprehensive overview of previously described and novel profiling primers and their genomic targets in potato through genetic mapping and comparative genomics. Furthermore, it is shown how genome-wide or fine mapping can be pursued by choosing different sets of profiling primers. A protocol for next-generation profiling is provided and will form the basis for novel applications. Using the current overview of genomic targets, a rational choice can be made for profiling primers to be employed.

[Clinical use of 30:70 controlled-release methylphenidate in the treatment of attention deficit hyperactivity disorder]. / Uso clínico de metilfenidato 30:70 de liberación modificada en el tratamiento del trastorno por déficit de atención/hiperactividad.

INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) is one of the most frequent reasons for visits in daily clinical practice, with a prevalence rate of 1-7% in Spain. The effectiveness of stimulants for the treatment of ADHD has been widely demonstrated and methylphenidate (MPD) is the most commonly used. There are currently several different immediate-release or extended-release formulations of MPD on the market. AIMS: To review the characteristics of the different formulations of MPD, with special attention paid to the studies on Equasym®, an extended-release preparation soon to be made available in Spain. The article also includes recommendations for clinical practice and the choice of drugs. DEVELOPMENT: Several studies have assessed the effectiveness of Equasym® versus placebo or in comparison to other MPD formulations. The extended-release preparations have a therapeutic action that is similar to that of the immediate-release versions, the difference between them being the plasma concentration profiles over time during the day, which are reflected in the pharmacodynamic effects. Equasym® is more effective in the morning, whereas other formulations, such as Concerta®, allow greater control of the symptoms in the afternoon. These differences are important when it comes to prescribing the treatment. CONCLUSIONS: One of the main advantages of having different formulations of MPD available is that it allows the professional to choose the drug that best suits the clinical features and needs of each patient. The individual response is the essential criterion in deciding on the most appropriate treatment.

Uso clínico de metilfenidato 30: 70 de liberación modificada en el tratamiento del trastorno por déficit de atención / hiperactividad / Clinical use of 30: 70 controlled-release methylphenidate in the treatment of attention deficit hyperactivity disorder

Introducción. El trastorno por déficit de atención/hiperactividad (TDAH) constituye uno de los motivos más frecuentes de consulta en la práctica clínica diaria, con una tasa de prevalencia del 1-7% en España. La eficacia de los estimulantes para el tratamiento del TDAH está ampliamente demostrada, y el metilfenidato (MTF) es el más comúnmente utilizado. En la actualidad se comercializan varias formulaciones de MTF de acción inmediata o prolongada. Objetivo. Revisar las características de las distintas formulaciones de MTF, con un enfoque especial en los estudios sobre Equasym ®, un preparado de acción prolongada próximamente disponible en España. También se incluyen recomendaciones para la práctica clínica y la elección de los fármacos. Desarrollo. Varios estudios han evaluado la eficacia de Equasym ® frente a placebo o en comparación con otras formulaciones de MTF. Los preparados de liberación prolongada tienen una acción terapéutica parecida a los de liberación inmediata, y se diferencian entre sí por los perfiles temporales de concentración plasmática durante el día, que se reflejan en los efectos farmacodinámicos. La eficacia de Equasym ® es mayor por la mañana, mientras que otras formulaciones, como Concerta ®, permiten un mejor control de los síntomas por la tarde. Estas diferencias son importantes a la hora de prescribir el tratamiento. Conclusiones. Disponer de diferentes formulaciones de MTF es beneficioso, porque permite elegir en cada caso el fármaco que mejor se ajuste a las características clínicas y necesidades de cada paciente. La respuesta individual es el criterio fundamental para decidir el tratamiento más adecuado (AU)

Introduction. Attention deficit hyperactivity disorder (ADHD) is one of the most frequent reasons for visits in daily clinical practice, with a prevalence rate of 1-7% in Spain. The effectiveness of stimulants for the treatment of ADHD has been widely demonstrated and methylphenidate (MPD) is the most commonly used. There are currently several different immediate-release or extended-release formulations of MPD on the market. Aims. To review the characteristics of the different formulations of MPD, with special attention paid to the studies on Equasym ®, an extended-release preparation soon to be made available in Spain. The article also includes recommendations for clinical practice and the choice of drugs. Development. Several studies have assessed the effectiveness of Equasym ® versus placebo or in comparison to other MPD formulations. The extended-release preparations have a therapeutic action that is similar to that of the immediaterelease versions, the difference between them being the plasma concentration profiles over time during the day, which are reflected in the pharmacodynamic effects. Equasym ® is more effective in the morning, whereas other formulations, such as Concerta ®, allow greater control of the symptoms in the afternoon. These differences are important when it comes to prescribing the treatment. Conclusions. One of the main advantages of having different formulations of MPD available is that it allows the professional to choose the drug that best suits the clinical features and needs of each patient. The individual response is the essential criterion in deciding on the most appropriate treatment (AU)

Algoritmos de derivación del TDAH: Consenso Geitadh / ADHD Algorithms for clinical pathways: GEITDAH consensus

El grupo de especial interés en TDAH (GEITADH) expone en este artículo su consenso sobre algoritmos de derivación en la asistencia para el paciente afecto de TDAH. Es un diseño sencillo realizado por un amplio número de profesionales de toda España con el objetivo de poder ser adaptado a necesidades asistenciales locales. Se revisan también otros algoritmos con influencia nacional

The Spanish Especial Interest Group on ADHD (GEITDAH) presents in this article its consensus on pathways for attending ADHD patients. This is a clear and simple consensus in order to facilitate the development of local algoritms inspired on it. Some ADHD algorithms used in the Spanish Health Services are reviewed

Consenso del GEITDAH sobre el trastorno por déficit de atención/hiperactividad / GEITDAH consensus on attention deficit hyperactivity disorder

El GEITDAH, Grupo de Especial Interés en el Trastorno por Déficit de Atención/Hiperactividad (TDAH), presenta en este artículo un consenso de expertos de toda España sobre el manejo del TDAH. Se han consensuado aspectos básicos que deberían ser el punto de partida para futuros consensos locales o regionales. Es también un objetivo de este consenso disminuir la variabilidad en la asistencia que se da en nuestro país al TDAH y servir de estímulo para fines docentes. Su reducida extensión permitirá una mayor difusión a fin de lograr todos estos fines de forma más efectiva. Las conclusiones del consenso se han articulado en torno a una introducción sobre aspectos básicos y recomendaciones para: diagnóstico, tratamiento (farmacológico y psicoterapéutico), flujo de pacientes y aspectos organizativos (AU)

In this article, the GEITDAH –the Spanish abbreviation of the Special Interest Group on Attention Deficit Hyperactivity Disorder (ADHD)– presents a consensus reached by experts in the management of ADHD from all over Spain. The consensus concerns fundamental aspects that should be the starting point for future local or regional consensus guides. Another aim of this consensus is also to reduce the amount of variability that occurs in the health care offered to patients with ADHD in our country, as well as to act as a stimulus in educational matters. That fact that it is not very long will make it more popular among greater numbers of people and this will allow these goals to be reached more effectively. The conclusions in the consensus guide have been constructed around an introduction dealing with basic aspects and recommendations for diagnosis, treatment (both pharmacological and psychotherapeutic), patient flow and organisational aspects (AU)

Respuesta inflamatoria durante los procesos de isquemia: moléculas de adhesión e inmunomodulación / Inflammatory response during ischaemic processes: adhesion molecules and immunomodulation

Introducción. Tras la isquemia cerebral se produce la muerte necrótica de las células afectadas por la ausencia de oxígeno y glucosa, especialmente de las neuronas. Esta necrosis desencadena la activación del sistema inmune y el inicio de la respuesta inflamatoria. El sistema nervioso central cuenta con células inflamatorias innatas como la microglía y los macrófagos, que poseen una función importante en la recepción y propagación de señales inflamatorias. Desarrollo. La respuesta inflamatoria se caracteriza por la expresión de mediadores inflamatorios y la invasión de células inflamatorias circulantes. El paso de los leucocitos a través del endotelio implica dos etapas coordinadas en el tiempo: la adhesión y la subsiguiente migración transendotelial. Por ello, las moléculas de adhesión en leucocitos y células endoteliales, como son las selectinas, las sialomucinas, la superfamilia de las inmunoglobulinas y las integrinas, constituyen moléculas clave que contribuyen al daño cerebral. Sin embargo, dicha respuesta precisa eliminar los restos celulares tanto necróticos como apoptóticos para iniciar los posibles procesos de reparación y plasticidad cerebral. Por tanto, la respuesta inflamatoria es una respuesta coordinada, y tras la activación de la inflamación se desencadena también una respuesta inmunosupresora y antiinflamatoria. Conclusiones. La inflamación se ha asociado a un aumento en el daño cerebral en pacientes con infarto cerebral, aunque es necesaria para activar los mecanismos de reparación. Por ello resulta preciso un estricto control de la respuesta inflamatoria después del infarto cerebral para reducir el daño del tejido afectado sin la inhibición de los mecanismos de reparación (AU)

Introduction. After cerebral ischemia, necrotic cell death occurs specially for neurons, mainly due to the privation of oxygen and glucose. Cell necrosis triggers the activation of the immune system followed by an inflammatory response. This reaction is characterized by the activation of astrocytes and microglia together with the infiltration of peripheral immune cells. Development. Both, microglia and inflammatory cells, including circulating peripheral inflammatory cells, get activated and release a plethora of inflammatory mediators, cytokines, chemokines, etc. Such released factors induce the overexpression of adhesion molecules, increasing the blood brain barrier permeability, thus favoring even more inflammatory cell infiltration. In the end, this contributes to increase brain damage. Inflammatory response is nevertheless necessary in order to eliminate cellular debris from both apoptotic and necrotic cells. It seems to be also implicated in the initiation of certain mechanisms responsible for brain repair and plasticity. As a result, the inflammatory response is a coordinated effort. Activation of inflammation triggers an immunosuppressant and anti-inflammatory response. A high rate of infections in patients suffering from stroke, together with increased serum levels of anti-inflammatory molecules in these patients, support this statement. The anti-inflammatory response could be interpreted as the organism attempting to control the heightened inflammatory response that occurs after cerebral ischemia. On the other hand, following an ischemic event, there are several new cerebral epitopes that get exposed to the immune system, which would never have been exposed under normal physiological conditions. Conclusion. Therefore immunosuppression after an ischemic accident hinders the development of auto-immune responses (AU)

[Inflammatory response during ischaemic processes: adhesion molecules and immunomodulation]. / Respuesta inflamatoria durante los procesos de isquemia: moléculas de adhesión e inmunomodulación.

INTRODUCTION: After cerebral ischemia, necrotic cell death occurs specially for neurons, mainly due to the deprivation of oxygen and glucose. Cell necrosis triggers the activation of the immune system followed by an inflammatory response. This reaction is characterized by the activation of astrocytes and microglia together with the infiltration of peripheral immune cells. DEVELOPMENT: Both, microglia and inflammatory cells, including circulating peripheral inflammatory cells, get activated and release a plethora of inflammatory mediators, cytokines, chemokines, etc. Such released factors induce the overexpression of adhesion molecules, increasing the blood brain barrier permeability, thus favoring even more inflammatory cell infiltration. In the end, this contributes to increase brain damage. Inflammatory response is nevertheless necessary in order to eliminate cellular debris from both apoptotic and necrotic cells. It seems to be also implicated in the initiation of certain mechanisms responsible for brain repair and plasticity. As a result, the inflammatory response is a coordinated effort. Activation of inflammation triggers an immunosuppressant and anti-inflammatory response. A high rate of infections in patients suffering from stroke, together with increased serum levels of anti-inflammatory molecules in these patients, support this statement. The anti-inflammatory response could be interpreted as the organism attempting to control the heightened inflammatory response that occurs after cerebral ischemia. On the other hand, following an ischemic event, there are several new cerebral epitopes that get exposed to the immune system, which would never have been exposed under normal physiological conditions. CONCLUSION: Therefore immunosuppression after an ischemic accident hinders the development of auto-immune responses.

Leukotriene B4-loaded microspheres: a new therapeutic strategy to modulate cell activation.

BACKGROUND: Leukotriene B4 (LTB4) is a potent inflammatory mediator that also stimulates the immune response. In addition, it promotes polymorphonuclear leukocyte phagocytosis, chemotaxis, chemokinesis and modulates cytokines release. Regarding chemical instability of the leukotriene molecule, in the present study we assessed the immunomodulatory activities conferred by LTB4 released from microspheres (MS). A previous oil-in-water emulsion solvent extraction-evaporation method was chosen to prepare LTB4-loaded MS. RESULTS: In the mice cremasteric microcirculation, intraescrotal injection of 0.1 ml of LTB4-loaded MS provoked significant increases in leukocyte rolling flux, adhesion and emigration besides significant decreases in the leukocyte rolling velocity. LTB4-loaded MS also increase peroxisome proliferator-activated receptor-alpha (PPARalpha) expression by murine peritoneal macrophages and stimulate them to generate nitrite levels. Monocyte chemoattractant protein-1 (MCP-1) and nitric oxide (NO) productions were also increased when human umbilical vein and artery endothelial cells (HUVECs and HUAECs, respectively) were stimulated with LTB4-loaded MS. CONCLUSION: LTB4-loaded MS preserve the biological activity of the encapsulated mediator indicating their use as a new strategy to modulate cell activation, especially in the innate immune response.

Sensitivity analysis of a parameterization of the stomatal component of the DO3SE model for Quercus ilex to estimate ozone fluxes.

A sensitivity analysis of a proposed parameterization of the stomatal conductance (g(s)) module of the European ozone deposition model (DO(3)SE) for Quercus ilex was performed. The performance of the model was tested against measured g(s) in the field at three sites in Spain. The best fit of the model was found for those sites, or during those periods, facing no or mild stress conditions, but a worse performance was found under severe drought or temperature stress, mostly occurring at continental sites. The best performance was obtained when both f(phen) and f(SWP) were included. A local parameterization accounting for the lower temperatures recorded in winter and the higher water shortage at the continental sites resulted in a better performance of the model. The overall results indicate that two different parameterizations of the model are needed, one for marine-influenced sites and another one for continental sites.

Tibouchina pulchra (Cham.) Cogn., a native Atlantic Forest species, as a bio-indicator of ozone: visible injury.

Tibouchina pulchra saplings were exposed to carbon filtered air (CF), ambient non-filtered air (NF) and ambient non-filtered air+40 ppb ozone (NF+O3) 8 h per day during two months. The AOT40 values at the end of the experiment were 48, 910 and 12,895 ppb h(-1), respectively, for the three treatments. After 25 days of exposure (AOT40=3871 ppb h(-1)), interveinal red stippling appeared in plants in the NF+O3 chamber. In the NF chamber, symptoms were observed only after 60 days of exposure (AOT40=910 ppb h(-1)). After 60 days, injured leaves per plant corresponded to 19% in NF+O3 and 1% in the NF treatment; and the average leaf area injured was 7% within the NF+O3 and 0.2% within the NF treatment. The extent of leaf area injured (leaf injury index) was mostly explained by the accumulated exposure of ozone (r2=0.89; p<0.05).