Targeting microglial KATP channels to treat neurodegenerative diseases: a mitochondrial issue

Neurodegeneration is a complex process involving different cell types and neurotransmitters. A common characteristic of neurodegenerative disorders is the occurrence of a neuroinflammatory reaction in which cellular processes involving glial cells, mainly microglia and astrocytes, are activated in response to neuronal death. Microglia do not constitute a unique cell population but rather present a range of phenotypes closely related to the evolution of neurodegeneration. In a dynamic equilibrium with the lesion microenvironment, microglia phenotypes cover from a proinflammatory activation state to a neurotrophic one directly involved in cell repair and extracellular matrix remodeling. At each moment, the microglial phenotype is likely to depend on the diversity of signals from the environment and of its response capacity. As a consequence, microglia present a high energy demand, for which the mitochondria activity determines the microglia participation in the neurodegenerative process. As such, modulation of microglia activity by controlling microglia mitochondrial activity constitutes an innovative approach to interfere in the neurodegenerative process. In this review, we discuss the mitochondrial KATP channel as a new target to control microglia activity, avoid its toxic phenotype, and facilitate a positive disease outcome.

Systematic review protocol to define classical IgE-associated diseases from birth to adolescence: the MeDALL study

BACKGROUND: Classical disease phenotypes are mainly based on descriptions of symptoms and the hypothesis that a given pattern of symptoms provides a diagnosis. With refined technologies there is growing evidence that disease expression in patients is much more diverse and subtypes need to be defined to allow a better targeted treatment. One of the aims of the Mechanisms of the Development of Allergy Project (MeDALL,FP7) is to re-define the classical phenotypes of IgE-associated allergic diseases from birth to adolescence, by consensus among experts using a systematic review of the literature and identify possible gaps in research for new disease markers. This paper describes the methods to be used for the systematic review of the classical IgE-associated phenotypes applicable in general to other systematic reviews also addressing phenotype definitions based on evidence. METHODS/DESIGN: Eligible papers were identified by PubMed search (complete database through April 2011). This search yielded 12,043 citations. The review includes intervention studies (randomized and clinical controlled trials) and observational studies (cohort studies including birth cohorts, case-control studies) as well as case series. Systematic and non-systematic reviews, guidelines, position papers and editorials are not excluded but dealt with separately. Two independent reviewers in parallel conducted consecutive title and abstract filtering scans. For publications where title and abstract fulfilled the inclusion criteria the full text was assessed. In the final step, two independent reviewers abstracted data using a pre-designed data extraction form with disagreements resolved by discussion among investigators. DISCUSSION: The systematic review protocol described here allows to generate broad,multi-phenotype reviews and consensus phenotype definitions. The in-depth analysis of the existing literature on the classification of IgE-associated allergic diseases through such a systematic review will 1) provide relevant information on the current epidemiologic definitions of allergic diseases, 2) address heterogeneity and interrelationships and 3) identify gaps in knowledge.

Systems medicine and integrated care to combat chronic noncommunicable diseases

We propose an innovative, integrated, cost-effective health system to combat major non-communicable diseases (NCDs), including cardiovascular, chronic respiratory, metabolic, rheumatologic and neurologic disorders and cancers, which together are the predominant health problem of the 21st century. This proposed holistic strategy involves comprehensive patient-centered integrated care and multi-scale, multi-modal and multi-level systems approaches to tackle NCDs as a common group of diseases. Rather than studying each disease individually, it will take into account their intertwined gene-environment, socio-economic interactions and co-morbidities that lead to individual-specific complex phenotypes. It will implement a road map for predictive, preventive, personalized and participatory (P4) medicine based on a robust and extensive knowledge management infrastructure that contains individual patient information. It will be supported by strategic partnerships involving all stakeholders, including general practitioners associated with patient-centered care. This systems medicine strategy, which will take a holistic approach to disease, is designed to allow the results to be used globally, taking into account the needs and specificities of local economies and health systems.

Relevance of death receptors in nervous system: role in the pathogenesis of neurodegenerative diseases and targets for therapy

L’apoptosi és un procés fisiològic que controla el nombre de cèl·lules en organismes superiors. L’apoptosi està estrictament regulada i s’ha vist que està implicada en la patogènesi d’algunes malalties del sistema nerviós. En aquest sentit, un excés de mort cel·lular contribueix a les malalties neurodegenerati- ves, mentre que, el seu dèficit és una de les raons del desenvolupament de tumors. El punt principal de regulació del procés apoptòtic és l’activació de les caspases, cisteïna-proteases que tenen especificitat pels residus aspàrtic. Les caspases es poden activar per dos mecanismes principals: (1) alliberament de citocrom C dels mitocondris alterats al citoplasma i (2) l’activació dels receptors de la membrana anomenats receptors de mort (DR, de l’anglès death receptor). Aquests receptors s’han caracteritzat extensament en el sistema immunitari, mentre que en el sistema nerviós les seves funcions són encara desconegudes. El present article se centra en el paper dels DR en la patogènesi de malalties neurodegeneratives i suggereix el seu potencial des del punt de vista terapèutic. També es descriuen diverses molècules intracel·lulars caracteritzades per la seva habilitat en la modulació dels DR. Entre elles, presentem dues noves proteïnes – lifeguard i FAIM – que s’expressen específicament al sistema nerviós.

Buccodental health and oral mucositis. Clinical study in patients with hematological diseases

Objectives: The objective of the present study is to assess whether a good buccodental status (evaluated by means of dentogingival indices), is associated with a lower incidence and severity of oral mucositis in patients with hematological diseases who receive treatment with chemotherapy or bone marrow transplant. Study design: The study was carried out on 97 patients admitted to the Hematology Service of the Hospital Duran y Reynals in Barcelona during 2002-2003. These patients received treatment with chemotherapy or conditioning prior to bone marrow transplant. A descriptive study was made, analyzing oral hygiene, one dental index, and two gingivales indices, and evaluating their relationship with the appearance of mucositis. Results: The patients with high plaque (PI) and gingival (GI) indices during chemotherapy presented a higher percentage of mucositis (77.4% and 65.7% respectively) against those who had little or no visible plaque. In the case of the PI, the differences were statistically significant (p=0.015). Likewise, patients who brushed their teeth 3 times/day presented mucositis in only 26.7% of cases, against those who did not brush, or brushed only once a day (65.9% and 68.4%), these differences also being statistically significant (p=0.013). The CAO showed similar results in patients with or without mucositis (7.59 and 7.03 respectively). Conclusions: In our study, a good gingival status as well as good oral hygiene during chemoradiotherapy is associated with a lower incidence and severity of mucositis.

Systems Medicine and Integrated Care to Combat Chronic Noncommunicable Diseases.

We propose an innovative, integrated, cost-effective health system to combat major non-communicable diseases (NCDs), including cardiovascular, chronic respiratory, metabolic, rheumatologic and neurologic disorders and cancers, which together are the predominant health problem of the 21st century. This proposed holistic strategy involves comprehensive patient-centered integrated care and multi-scale, multi-modal and multi-level systems approaches to tackle NCDs as a common group of diseases. Rather than studying each disease individually, it will take into account their intertwined gene-environment, socio-economic interactions and co-morbidities that lead to individual-specific complex phenotypes. It will implement a road map for predictive, preventive, personalized and participatory (P4) medicine based on a robust and extensive knowledge management infrastructure that contains individual patient information. It will be supported by strategic partnerships involving all stakeholders, including general practitioners associated with patient-centered care. This systems medicine strategy, which will take a holistic approach to disease, is designed to allow the results to be used globally, taking into account the needs and specificities of local economies and health systems.

Using transient elastography to detect chronic liver diseases in a primary care nurse consultancy

Background: Chronic liver diseases (CLDs) are significant causes of death in adults in many countries and are usually diagnosed at late stages. Early detection may allow time for treatment to prevent disease progression. Objectives: The aim of this study was to assess the feasibility of screening for unrecognized CLDs in a primary care nurse consultancy and report findings from screening. Methods: Two experienced nurses in a primary care nurse consultancy were trained to perform transient elastography (TE). Subjects aged from 18 to 70 years were identified randomly from the health registry and invited to participate in a feasibility pilot study. Exclusion criteria were past or current history of liver diseases. Nurses collected demographic and clinical data and performed TE tests using Fibroscan tomeasure liver stiffness; a cutoff score of 6.8 kPa or greater was used as an indicator of the presence of CLD with fibrosis. Results: Accurate measurements were obtained in 495 of 502 participants (98.6%). Prevalence of elevated liver stiffness was observed in 28 of 495 subjects (5.7%). Compared to patients with normal liver stiffness, patients with increased liver stiffness were older, were more frequently male, and had higher frequency of metabolic syndrome. Nonalcoholic fatty liver was the most common cause of CLD. Discussion: Following training in procedures for conducting TE, nurses in a primary care clinic were able to detect unrecognized CLDs in presumably healthy subjects. Early detection of CLDs is feasible in primary care clinics and may facilitate identification of undiagnosed CLD in adults.

Neurodegenerative diseases: A protein misfolding consequence

Protein misfolding and aggregation into amyloid-like structures is related with an increasing number of both non-neuropathic (either localized or systemic) and neurodegenerative human disorders. Decrypting the mechanisms and implications underlying amyloid assemblies has become a central issue in biology and medicine. Compelling evidence show that the formation of amyloid aggregates has a negative impact in cell physiology, entailing the cell dysfunction and finally apoptosis and cell death. The aim of the present review is to illustrate the currently status of the most common and/or debilitating conformational diseases, from Alzheimer to prion diseases.

Neurodegenerative diseases: A protein misfolding consequence

Protein misfolding and aggregation into amyloid-like structures is related with an increasing number of both non-neuropathic (either localized or systemic) and neurodegenerative human disorders. Decrypting the mechanisms and implications underlying amyloid assemblies has become a central issue in biology and medicine. Compelling evidence show that the formation of amyloid aggregates has a negative impact in cell physiology, entailing the cell dysfunction and finally apoptosis and cell death. The aim of the present review is to illustrate the currently status of the most common and/or debilitating conformational diseases, from Alzheimer to prion diseases.

Potential of caveolae in the therapy of cardiovascular and neurological diseases.

Caveolae are membrane micro-domains enriched in cholesterol, sphingolipids and caveolins, which are transmembrane proteins with a hairpin-like structure. Caveolae participate in receptor-mediated trafficking of cell surface receptors and receptor-mediated signaling. Furthermore, caveolae participate in clathrin-independent endocytosis of membrane receptors. On the one hand, caveolins are involved in vascular and cardiac dysfunction. Also, neurological abnormalities in caveolin-1 knockout mice and a link between caveolin-1 gene haplotypes and neurodegenerative diseases have been reported. The aim of this article is to present the rationale for considering caveolae as potential targets in cardiovascular and neurological diseases.

Food Frequency Questionnaires (FFQ) para el estudio del consumo de cacao en estudiantes de ciencias de la salud

Tot i que el cacau i la xocolata són una gran font de polifenols, aquests aliments no es troben entre les fonts alimentàries de polifenols més consumides. Algunes dades suggereixen un aport inferior al 10% de polifenols a través d’aquests. Aquest fet podria ser causa de les diferents metodologies i l'enfocament dels qüestionaris de freqüència de consum d'aliments (FFQ) utilitzats en aquests estudis. La majoria de FFQ validats utilitzen una extensa llista d'aliments per a les fruites i verdures, però no distingeixen adequadament les diverses fonts de xocolata i cacau. Aquests fets recolzen la necessitat d'una avaluació del consum de productes de cacau per tal de poder conèixer la ingesta real de cacau, especialment en la població jove, on la xocolata és un aliment consumit freqüentment.

FFQ para el estudio del consumo de cacao (portugués)

Cocoa has been highlighted as a food with potential benefits to human health due to it being animportant source of polyphenols. However, few studies show the contribution of cocoa andchocolate products in polyphenol intake. The aim of this work was to develop and validate afood frequency questionnaire (FFQ) evaluating the intake of food products containing cocoa (CFFQ).A sample of university students was recruited to complete the 90-item questionnaire inSpain and therefore in Spanish (http://diposit.ub.edu/dspace/handle/2445/60475) and in Portugalin a Portuguese version, which is the present document. The developed FFQ questionnaire canbe considered as a valid option for assessing the consumption frequency of cocoa- andchocolate-derived products, thereby allowing the evaluation of cocoa polyphenol intake infurther studies.

Principales patrones de uso del suelo como generadores de ingresos económicos de los pequeños productores de café y cacao en la Amazonía norte del Ecuador

El sector agrícola de la Amazonía norte de Ecuador, está conformada por miles de pequeños agricultores que fundamentan principalmente sus ingresos en los cultivos de café, cacao. La necesidad de contar con mayores ingresos económicos provoca que los agricultores incursionen en cultivos. Esta condición determina que los procesos de producción tengan diferentes comportamientos frente al uso del suelo. Determinar los principales patrones de uso del suelo como generadores de ingresos económicos, permite tener una mejor óptica de cómo está diversificada la producción en términos de dinero. Este artículo inicia abordando algunas consideraciones necesarias para enmarcarse en cómo ha evolucionado la forma de uso del suelo, se exponen distintos criterios de investigadores que explican este comportamiento. Seguidamente se analiza cómo los productores se embarcan en esa búsqueda por incrementar sus rentas adoptando diversas formas de cultivo. Posteriormente se establecen cuatro tipologías de productores muy bien definidas en torno al uso del suelo. Con los resultados obtenidos se entabla una discusión, que permite mostrar el porqué de ciertos comportamientos productivos. Finalmente, se presentan conclusiones en función de las tipologías encontradas acompañadas de información válida para la aplicación de políticas públicas, orientadas a mejorar los ingresos de los productores.