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1.
J. physiol. biochem ; 79(4): 719-730, nov. 2023. ilus
Artigo em Inglês | IBECS | ID: ibc-227547

RESUMO

Sonic hedgehog (SHH) signaling is vital for cell differentiation and proliferation during embryonic development, yet its role in cardiac, cerebral, and vascular pathophysiology is under debate. Recent studies have demonstrated that several compounds of SHH signaling regulate ion channels, which in turn affect the behavior of target cells. Some of these ion channels are involved in the cardio-cerebrovascular system. Here, we first reviewed the SHH signaling cascades, then its interaction with ion channels, and their impact on cardio-cerebrovascular diseases. Considering the complex cross talk of SHH signaling with other pathways that also affect ion channels and their potential impact on the cardio-cerebrovascular system, we highlight the necessity of thoroughly studying the effect of SHH signaling on ion homeostasis, which could serve as a novel mechanism for cardio-cerebrovascular diseases. (AU)


Assuntos
Humanos , Feminino , Gravidez , Transtornos Cerebrovasculares , Proteínas Hedgehog/metabolismo , Diferenciação Celular , Canais Iônicos/metabolismo , Transdução de Sinais
2.
Arch. bronconeumol. (Ed. impr.) ; 53(1): 19-26, ene. 2017. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-159146

RESUMO

La gripe es una enfermedad contagiosa altamente prevalente y con significativa morbimortalidad. El tratamiento disponible con fármacos antivirales, de ser administrado de forma precoz, puede reducir el riesgo de complicaciones severas; sin embargo, muchos tipos de virus desarrollan resistencia a estos fármacos, reduciendo notablemente su efectividad. Ha habido un gran interés en el desarrollo de nuevas opciones terapéuticas para combatir la enfermedad. Una gran variedad de fármacos han demostrado tener actividad antiinfluenza, pero aún no están disponibles para su uso en la clínica. Muchos de ellos tienen como objetivo componentes del virus, mientras que otros son dirigidos a elementos de la célula huésped que participan en el ciclo viral. Modular los componentes del huésped es una estrategia que minimiza el desarrollo de cepas resistentes, dado que estos no están sujetos a la variabilidad genética que tiene el virus. Por otro lado, la principal desventaja es que existe un mayor riesgo de efectos secundarios asociados al tratamiento. El objetivo de la presente revisión es describir los principales agentes farmacológicos disponibles en la actualidad, así como los nuevos fármacos en estudio con potencial beneficio en el tratamiento de la gripe


Influenza is a very common contagious disease that carries significant morbidity and mortality. Treatment with antiviral drugs is available, which if administered early, can reduce the risk of severe complications. However, many virus types develop resistance to those drugs, leading to a notable loss of efficacy. There has been great interest in the development of new drugs to combat this disease. A wide range of drugs has shown anti-influenza activity, but they are not yet available for use in the clinic. Many of these target viral components, which others are aimed at elements in the host cell which participate in the viral cycle. Modulating host components is a strategy which minimizes the development of resistance, since host components are not subject to the genetic variability of the virus. The main disadvantage is the risk of treatment-related side effects. The aim of this review is to describe the main pharmacological agents currently available and new drugs in the pipeline with potential benefit in the treatment of influenza


Assuntos
Humanos , Influenza Humana/tratamento farmacológico , Vacinas contra Influenza/administração & dosagem , Medicamentos Compostos contra Resfriado, Influenza e Alergia/uso terapêutico , Fatores de Risco , Antivirais/uso terapêutico , Canais Iônicos/antagonistas & inibidores , Nucleoproteínas/antagonistas & inibidores
3.
J. physiol. biochem ; 72(2): 293-302, jun. 2016. tab, graf, ilus
Artigo em Inglês | IBECS | ID: ibc-168273

RESUMO

Bisoprolol, an antagonist of β1-adrenergic receptors, is effective in reducing the morbidity and mortality in patients with heart failure (HF). It has been found that HF is accompanied with dysfunction of the sinoatrial node (SAN). However, whether bisoprolol reverses the decreased SAN function in HF and how the relevant ion channels in SAN change were relatively less studied. SAN function and messenger RNA (mRNA) expression of sodium channels and hyperpolarization-activated cyclic nucleotide-gated (HCN) channel subunits were assessed in sham-operated rats, abdominal arterio-venous shunt (volume overload)-induced HF rats, and bisoprolol- treated HF rats. SAN cells of rats were isolated by laser capture microdissection. Quantitative real-time PCR analysis was used to quantify mRNA expression of sodium channels and HCN channel subunits in SAN. Intrinsic heart rate declined and sinus node recovery time prolonged in HF rats, indicating the suppressed SAN function, which could be improved by bisoprolol treatment. Nav1.1, Nav1.6, and HCN4 mRNA expressions were reduced in SAN in HF rats compared with that in control rats. Treatment with bisoprolol could reverse both the SAN function and the Nav1.1, Nav1.6, and HCN4 mRNA expression partially. These data indicated that bisoprolol is effective in HF treatment partially due to improved SAN function by reversing the down-regulation of sodium channels (Nav1.1 and Nav1.6) and HCN channel (HCN4) subunits in SAN in failing hearts (AU)


No disponible


Assuntos
Animais , Masculino , Antagonistas de Receptores Adrenérgicos beta 1/uso terapêutico , Bisoprolol/uso terapêutico , Cardiotônicos/uso terapêutico , Modelos Animais de Doenças , Insuficiência Cardíaca/tratamento farmacológico , Canais Iônicos/agonistas , Nó Sinoatrial , Remodelamento Atrial , Regulação da Expressão Gênica , Canal de Sódio Disparado por Voltagem NAV1.1 , Canal de Sódio Disparado por Voltagem NAV1.6 , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização , Microdissecção e Captura a Laser , Ratos Sprague-Dawley
4.
J. physiol. biochem ; 72(1): 25-32, mar. 2016. tab, graf
Artigo em Inglês | IBECS | ID: ibc-168204

RESUMO

Obesity, a complex metabolic disorder, is characterized by mitochondrial dysfunction and oxidative stress. Increased expression of uncoupling protein 2 (UCP2) during obesity is an adaptive response to suppress the production of reactive oxygen species. The aims of this study were to compare the expression of UCP2 in diet-induced obese Wistar rats that differed according to age and their severity of obesity, and to compare UCP2 expression in the liver and muscle of these rats. UCP2 messenger RNA and protein expression was increased 4.6-fold (p < 0.0001) and 3.0-fold (p < 0.05), respectively, in the liver of the older and heavier rats. In contrast, UCP2 expression was decreased twofold (p < 0.005) in the muscle of these rats, while UCP3 messenger RNA (mRNA) was increased twofold (p < 0.01). Peroxisome proliferator-activated receptor alpha (PPARα) was similarly increased (3.0-fold, p < 0.05) in the liver of the older and more severe obese rats. Total protein content was increased (2.3-fold, p < 0.0001), while 5' adenosine monophosphate-activated protein kinase (AMPK) activity was decreased (1.3-fold, p = 0.05) in the liver of the older, heavier rats. No difference in total protein content and AMPK expression was observed in the muscle of these rats. This study showed that the expression of UCP2 varies according to age and the severity of obesity and supports the widely held notion that increased UCP2 expression is an adaptive response to increased fatty acid β-oxidation and reactive oxygen species production that occurs during obesity. An understanding of metabolic adaptation is imperative to gain insight into the underlying causes of disease, thus facilitating intervention strategies to combat disease progression (AU)


No disponible


Assuntos
Animais , Masculino , Ratos , Obesidade/metabolismo , Fatores Etários , Proteínas Mitocondriais/metabolismo , Canais Iônicos/metabolismo , Ratos Wistar , Proteína Desacopladora 2
5.
Rev. esp. cardiol. (Ed. impr.) ; 68(5): 398-407, mayo 2015. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-138510

RESUMO

Introducción y objetivos: La taquicardia ventricular polimórfica catecolaminérgica es una enfermedad maligna que se debe a mutaciones en las proteínas que controlan la homeostasis del Ca2+. Aunque el fenotipo se caracteriza por arritmias ventriculares polimórficas desencadenadas por el estrés, no se han caracterizado plenamente las arritmias supraventriculares que en ocasiones las acompañan. Métodos: Veinticinco miembros de una familia española en la que había habido varias muertes súbitas fueron evaluados mediante electrocardiograma, pruebas de esfuerzo y prueba de desenmascaramiento con adrenalina opcionalmente. Se realizó secuenciación selectiva deRyR2 en un miembro afectado y un cribado en cascada al resto de la familia. Se generó la mutación RyR2R420Q en células HEK-293 mediante mutagénesis dirigida, con objeto de realizar estudios funcionales in vitro. Resultados: Las pruebas de esfuerzo desenmascararon taquicardia ventricular polimórfica catecolaminérgica en 8 familiares (sensibilidad del 89%; valor predictivo positivo del 100%; valor predictivo negativo del 93%), todos ellos portadores de una mutación heterocigota RyR2R420Q, que estaba presente también en el caso probando y en una chica joven sin prueba de esfuerzo, lo que corresponde a una penetrancia del 91% al final del seguimiento. Es de destacar que en los pacientes se identificó bradicardia sinusal, arritmias auriculares y de la unión y/u ondas U gigantes tras esfuerzo. Tras la permeabilización y en las células intactas, las células que expresaban RyR2R420Q mostraron un pico de liberación de Ca2+ menor que el de las célulasRyR2 no mutado o wild-type. Sin embargo, a una concentración de Ca2+ intracelular fisiológica, equivalente a la concentración citosólica diastólica, las células RyR2R420Q liberaban más Ca2+ y oscilaban con mayor rapidez que las células con RyR2 no mutado o wild-type. Conclusiones: La mutación missense RyR2R420Q se identificó en el extremo aminoterminal del gen RyR2 en esta familia muy sintomática. Es de destacar que esta mutación se asocia a bradicardia sinusal, arritmias auriculares y de la unión y ondas U gigantes. En conjunto, los estudios de expresión heteróloga funcional indican que la mutación RyR2R420Q causa un comportamiento aberrante del canal, con pérdida o ganancia de función, según cuál sea la concentración de Ca2+ intracelular citosólica


Introduction and objectives: Catecholaminergic polymorphic ventricular tachycardia is a malignant disease, due to mutations in proteins controlling Ca2+ homeostasis. While the phenotype is characterized by polymorphic ventricular arrhythmias under stress, supraventricular arrhythmias may occur and are not fully characterized. Methods: Twenty-five relatives from a Spanish family with several sudden deaths were evaluated with electrocardiogram, exercise testing, and optional epinephrine challenge. Selective RyR2 sequencing in an affected individual and cascade screening in the rest of the family was offered. The RyR2R420Q mutation was generated in HEK-293 cells using site-directed mutagenesis to conduct in vitro functional studies. Results: The exercise testing unmasked catecholaminergic polymorphic ventricular tachycardia in 8 relatives (sensitivity = 89%; positive predictive value = 100%; negative predictive value = 93%), all of them carrying the heterozygous RyR2R420Q mutation, which was also present in the proband and a young girl without exercise testing, a 91% penetrance at the end of the follow-up. Remarkably, sinus bradycardia, atrial and junctional arrhythmias, and/or giant post-effort U-waves were identified in patients. Upon permeabilization and in intact cells, the RyR2R420Q expressing cells showed a smaller peak of Ca2+ release than RyR2 wild-type cells. However, at physiologic intracellular Ca2+ concentration, equivalent to the diastolic cytosolic concentration, the RyR2R420Q released more Ca2+ and oscillated faster than RyR2 wild-type cells. Conclusions The missense RyR2R420Q mutation was identified in the N-terminus of the RyR2 gene in this highly symptomatic family. Remarkably, this mutation is associated with sinus bradycardia, atrial and junctional arrhythmias, and giant U-waves. Collectively, functional heterologous expression studies suggest that the RyR2R420Q behaves as an aberrant channel, as a loss- or gain-of-function mutation depending on cytosolic intracellular Ca2+ concentration


Assuntos
Humanos , Taquicardia Ventricular/genética , Morte Súbita Cardíaca/etiologia , Catecolaminas , Mutação/genética , Distúrbios do Metabolismo do Cálcio/fisiopatologia , Canais Iônicos/fisiologia , Eletrocardiografia
7.
Rev. esp. cardiol. (Ed. impr.) ; 62(11): 1297-1315, nov. 2009. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-73904

RESUMO

El síndrome de Brugada, descrito por primera vez en 1992, se caracteriza por un patrón electrocardiográfico característico en precordiales derechas y la predisposición a presentar arritmias ventriculares y muerte súbita. El síndrome de Brugada se incluye entre las canalopatías, trastornos eléctricos primarios que característicamente no asocian cardiopatía estructural concomitante. En los últimos años, gracias a una intensa labor científica tanto básica como clínica, hemos podido identificar múltiples mutaciones causales, y asimismo comprender cuáles son los mecanismos implicados en la aparición del fenotipo característico y los determinantes del pronóstico clínico en los pacientes. Sin embargo, todavía persisten múltiples preguntas sin resolver que mantienen activa la investigación sobre el tema. Este artículo revisa nuestro conocimiento actual sobre el síndrome de Brugada y trata de recoger los principales estudios básicos y clínicos que han contribuido más significativamente a avanzar en nuestra comprensión de esta enfermedad (AU)


First described in 1992, Brugada syndrome is characterized by a specific electrocardiographic pattern in the right precordial leads and susceptibility to ventricular arrhythmias and sudden death. Brugada syndrome is included among the channelopathies, primary electrical disorders that, characteristically, are not associated with concomitant structural cardiac abnormalities. In recent years, substantial preclinical and clinical research has led to the identification of multiple causative mutations and to understanding of the mechanisms underlying the development of the characteristic phenotype and of the factors that determine clinical prognosis in patients. Nevertheless, there remain numerous unresolved questions which provide an impetus for ongoing active research into the condition. This article provides a summary of what is currently known about Brugada syndrome and an overview of the principal preclinical and clinical studies that have made the most significant contributions to our understanding of the condition (AU)


Assuntos
Humanos , Síndrome de Brugada/epidemiologia , Morte Súbita Cardíaca/epidemiologia , Canalopatias/epidemiologia , Síndrome de Brugada/genética , Canais Iônicos/genética , Fibrilação Ventricular/genética
8.
Rev. neurol. (Ed. impr.) ; 49(10): 541-546, 15 nov., 2009. tab
Artigo em Espanhol | IBECS | ID: ibc-108070

RESUMO

Introducción. La epilepsia es uno de los mayores trastornos neurológicos y afecta a alrededor del 0,5-2% de la población mundial. Se caracteriza por la aparición de crisis espontáneas y recurrentes. Se considera a la epilepsia del lóbulo temporal (ELT) como un síndrome adquirido multifactorial, que aparece como un efecto secundario a diferentes lesiones. Los avances realizados en biología molecular han facilitado la detección de numerosas alteraciones en genética molecular que pueden tener un efecto patógeno en las ELT. Recientemente, numerosos autores muestran evidencias de la existencia de componentes genéticos como origen de algunos tipos de ELT. Desarrollo. Se plantea como objetivo revisar las mutaciones y los polimorfismos relacionados con la epilepsia del lóbulo temporal que se han descrito en la literatura científica y su contribución a la fisiopatología de la epileptogénesis. Se revisan los genes LGI1, de la interleucina-1beta, de la prodinorfina, PRNP, el que codifica para el receptor GABAB tipo 1, SCN1A, SCN1B, KCNA1, KCND2 y ApoE. Conclusión. La ELT es una enfermedad compleja que puede depender tanto de la predisposición genética como de otros factores que contribuyen a su desarrollo. Es necesario realizar estudios funcionales para poder correlacionar su base molecular y su desarrollo (AU)


Introduction. Epilepsy is one of the major neurological disorders characterized by spontaneous and recurrent seizures. Traditionally temporal lobe epilepsy (TLE) was considered as a multifactorial syndrome due to environmental factors. Advances in molecular biology have facilitated the detection of many genetic alterations that may have a pathogenic effect in ELT. Recently, many authors show evidence about the existence of genetic components as the source of some types of ELT. Development. This review aims to provide an overview of mutations and polymorphisms associated with temporal lobe epilepsy, which have been described in scientific literature and its contribution to the pathophysiology of epileptogenesis. We have reviewed the following genes; LGI1, PDYN (prodynorphin), interleucine 1beta, PRPN (prion protein), ApoE (apolipoprotein E), GABBR1, SCN1A, SCN1B, KCNA1, KCND2. Conclusion. The ELT is a complex disease and its development could depend on either genetics factors or other factors. Functional studies are necessary in order to correlate its molecular basis and their development (AU)


Assuntos
Humanos , Epilepsia do Lobo Temporal/genética , Canais de Sódio/genética , Interleucina-1beta/genética , Príons/genética , Mutação/genética , Polimorfismo Genético , Canais Iônicos , Predisposição Genética para Doença , Mutação/genética , Polimorfismo Genético , Canais Iônicos , Predisposição Genética para Doença
9.
Reumatol. clín. (Barc.) ; 5(extr.2): 27-31, ago. 2009.
Artigo em Espanhol | IBECS | ID: ibc-78390

RESUMO

La fibromialgia (FM) es una patología crónica, cuyo síntoma principal es el dolor, el cual no responde a los analgésicos tradicionales. Las características clínicas y los diferentes hallazgos neurofisiológicos en estos pacientes apuntan a un proceso de sensibilización central del sistema nociceptivo como eje fisiopatológico central en esta enfermedad. El conocimiento del funcionamiento del sistema nociceptivo y de su comportamiento en esta enfermedad nos ha aportado en los últimos años nuevas posibilidades en el abordaje terapéutico. Así, están siendo desarrollados fármacos con un mecanismo de acción diferencial, que pueden ejercer una modulación de la actividad del sistema nociceptivo capaz de producir analgesia donde otros fármacos han fracasado. Diferentes fármacos con capacidad de incrementar la actividad de las bioaminas implicadas en los procesos de inhibición nociceptiva y otros dirigidos a ejercer una disminución de la excitabilidad del sistema, a través de los canales iónicos, están siendo probados con beneficio en los pacientes con FM y pueden conformar un perfil farmacológico neuromodulador más racional en esta enfermedad. En este artículo se revisan las diferentes estrategias farmacológicas con evidencia científica y se apuntan algunas líneas de futuro que fortalezcan el cambio terapéutico que se está produciendo en el abordaje farmacológico de estos pacientes (AU)


Fibromyalgia is a chronic pathology and its main symptom is pain which usually does not respond to traditional analgesia. Its clinical characteristics and the diverse neurophysiologic findings in these patients point to a central sensitization process of the nociceptive system as the central physiopathologic axis in this disease. The knowledge of the nociceptive system functioning and its behavior in this disease has led, in the past few years, to new possibilities for the therapeutic approach. In that way, drugs with a differential mechanism of action, allowing a modulation of the nociceptive system capable of producing analgesia where other medications have failed are being developed. Different drugs with the capacity increasing the activity of biologically active amines implicated in the nociceptive inhibition process and others which are destined to reduce the excitability of the system through ion channels, are being tested with some benefit in Fibromyalgia patients and may constitute a more rational neuromodulating drug profile for this disease. This article reviews the different pharmacological strategies supported by scientific evidence and points to some future research lines that fortifies the therapeutic change taking place in the treatment approach of these patients (AU)


Assuntos
Humanos , Fibromialgia/tratamento farmacológico , Analgesia/métodos , Neurotransmissores/farmacocinética , Inibidores Seletivos de Recaptação de Serotonina/farmacocinética , Inibidores da Captação de Dopamina/farmacocinética , GABAérgicos/uso terapêutico , Norepinefrina/antagonistas & inibidores , Canais Iônicos/antagonistas & inibidores
10.
Rev. neurol. (Ed. impr.) ; 48(7): 357-364, 1 abr., 2009. ilus
Artigo em Espanhol | IBECS | ID: ibc-94908

RESUMO

Resumen. Introducción. El dolor es resultado del procesamiento de una gran cantidad de señales producidas a diferentes niveles del sistema nervioso central y periférico, que se generan en respuesta a estímulos provenientes del medio ambiente o del organismo mismo. Una de las estrategias para generar nuevos analgésicos consiste en el estudio de las bases moleculares que subyacen en la detección de los estímulos dolorosos, es decir, los receptores. Un receptor de gran importancia para la fisiología sensorial y del dolor es el TRPV1, encargado de la detección de estímulos mecánicos, químicos y térmicos. Objetivo. Discutir los aspectos estructurales y funcionales del canal TRPV1, además de su participación en algunos procesos patológicos y las posibles perspectivas de investigación clínica. Desarrollo. La activación del TRPV1 en neuronas sensitivas genera señalesque llegan al sistema nervioso central, donde se interpretan como dolor, además de provocar la liberación periférica de sustancias proinflamatorias que sensibilizan a otras neuronas a estímulos subsecuentes. El TRPV1 es un receptor estructuralmente similar a otros canales iónicos dependientes de voltaje, con la capacidad de detectar e integrar diversos estímulos del medio ambiente, como temperaturas elevadas nocivas o agentes irritantes. Además, la actividad de este canal se acopla a diversas cadenas de señalización relacionadas con procesos de inflamación. Conclusión. La participación central del TRPV1en la fisiología del dolor resulta alentadora para el desarrollo de fármacos dirigidos a este receptor que puedan utilizarse en el tratamiento de diversos tipos de dolor (AU)


Summary. Introduction. Pain results from the processing of a large number of signals produced at different levels of the central and peripheral nervous system, which are generated in response to stimuli from the environment or from the organism itself. One of the strategies for generating new analgesics consists in studying the molecular bases that underlie the detection of painful stimuli, that is to say, the receptors. One receptor that plays a very important role in sensory and pain physiology is TRPV1, which is responsible for detecting mechanical, chemical and thermal stimuli. Aims. The aim of this study is to discuss the structural and functional aspects of the TRPV1 channel, as well as its participation in certain pathological processes and the possible perspectives for clinical research. Development. TRPV1 activation in sensory neurons generates signals that reach the central nervous system, where they are interpreted as pain, as well as triggering the peripheral release of proinflammatory substances that make other neurons sensitive to subsequent stimuli. TRPV1 is a receptor that is structurally similar to other voltage-dependent ion channels, with the capacity to detect and integrate several different stimuli from the environment, such as dangerously high temperatures or irritants. Furthermore, the activity of this channel is linked to several signalling chains related with inflammatory processes. Conclusions. The central role of TRPV1 in the physiology of pain will surely encourage the development of drugs aimed at this receptor which can be used in the treatment of several types of pain (AU)


Assuntos
Humanos , Dor/tratamento farmacológico , Analgesia/métodos , Canais Iônicos , Canais de Cátion TRPV , Inflamação/fisiopatologia , Nociceptores , Mediadores da Inflamação/fisiologia
11.
Rev. esp. cardiol. (Ed. impr.) ; 62(4): 422-436, abr. 2009. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-72646

RESUMO

La biomedicina ha experimentado en los últimos 50 años unos avances sorprendentes que han permitido obtener espectaculares mejoras en la prevención, el diagnóstico y el tratamiento de muchas enfermedades. La cardiología, a pesar de que ha ido incorporando estos avances a un ritmo más lento, hoy está completamente sumergida en esta revolución e incluso es una de las especialidades médicas más innovadoras. Se sigue investigando para lograr nuevos avances en genética y biología molecular que nos abren, día a día, nuevos métodos de prevención, diagnóstico y tratamiento clínico de las afecciones cardiacas más severas. Así pues, para el cardiólogo clínico es imprescindible adquirir conocimientos básicos en genética y biología molecular, ya que este campo está influyendo cada vez más en la práctica clínica (AU)


The remarkable advances that have taken place in biomedicine over the past 50 years have resulted in dramatic improvements in the prevention, diagnosis, and treatment of many diseases. Although cardiology has adopted these advances at a relatively slow pace, today it is fully immersed in this revolution and has become one of the most innovative medical specialties. Research is continuing to give rise to new developments in genetics and molecular biology that lead, almost daily, to innovative ways of preventing, diagnosing, and treating the most severe forms of heart disease. Consequently, it is essential that clinical cardiologists have some basic knowledge of genetics and molecular biology as these disciplines are having an increasing influence on clinical practice (AU)


Assuntos
Humanos , Masculino , Feminino , Arritmias Cardíacas/genética , Cardiopatias/genética , Cariótipo , Canalopatias/genética , Fibrilação Atrial/genética , Arritmias Cardíacas/fisiopatologia , Cardiopatias/fisiopatologia , Canais de Cálcio/genética , Canais Iônicos/genética , Canais Iônicos/fisiologia , Canais de Potássio/genética , Canais de Potássio/fisiologia
12.
Clin. transl. oncol. (Print) ; 11(1): 11-19, ene. 2009. ilus
Artigo em Inglês | IBECS | ID: ibc-123570

RESUMO

A new theory about the development of solid tumours is emerging from the idea that solid tumours, like normal adult tissues, contain stem cells (called cancer stem cells) and arise from them. Genetic mutations encoding for proteins involved in critical signalling pathways for stem cells such as BMP, Notch, Hedgehog and Wnt would allow stem cells to undergo uncontrolled proliferation and form tumours. Taking into account that cancer stem cells (CSCs) would represent the real driving force behind tumour growth and that they may be drug resistant, new agents that target the above signalling pathways could be more effective than current anti-solid tumour therapies. In the present paper we will review the molecular basis of the Notch signalling pathway. Additionally, we will pay attention to their role in adult stem cell self-renewal, and cell fate specification and differentiation, and we will also review evidence that supports their implication in cancer (AU)


No disponible


Assuntos
Humanos , Animais , Masculino , Feminino , Células-Tronco Neoplásicas/metabolismo , Receptores Notch/metabolismo , Transdução de Sinais/fisiologia , Receptores Notch/química , Canais Iônicos/fisiologia
14.
Clin. transl. oncol. (Print) ; 10(3): 143-147, mar. 2008. ilus
Artigo em Inglês | IBECS | ID: ibc-123424

RESUMO

The nuclear factor kappa B (NFkappaB) signalling pathway regulates the expression of hundreds of genes that are involved in different cellular processes such as cell proliferation, survival, stress responses, cellular immunity and inflammation. Its aberrant regulation is involved in several pathologies, but its relevance in cellular transformation and cancer development has been extensively studied. Mutations in the core components of NFkappaB as well as in the cellular machinery that regulates its activation have been found in many types of tumours. On the other hand, its role in promoting cell survival is an important obstacle in many cancer therapies. The development of chemical inhibitors that block NFkappaB activation acting either directly on IKKs or on the proteosome machinery has shown antitumour and proapoptotic activity both in preclinical and clinical studies (AU)


No disponible


No disponible


Assuntos
Humanos , Masculino , Feminino , NF-kappa B/metabolismo , NF-kappa B/fisiologia , Neoplasias/metabolismo , Transdução de Sinais/fisiologia , Proteínas I-kappa B/metabolismo , Neoplasias/patologia , Neoplasias/terapia , Canais Iônicos/metabolismo , Canais Iônicos/fisiologia
15.
Rev. esp. cardiol. (Ed. impr.) ; 61(1): 66-75, ene. 2008. ilus, tab
Artigo em Es | IBECS | ID: ibc-058566

RESUMO

En 2002, un grupo de investigadores en electrofisiología celular, cardiología, genética de poblaciones, epidemiología, proteómica, biología molecular, bioinformática y estadística decidió afrontar el reto de analizar los mecanismos y la genética de la hipertensión arterial (HTA). Se identificaron mecanismos relacionados con la regulación de la función de la musculatura lisa arterial por canales iónicos. La Red HERACLES (Hipertensión Esencial: Red de Análisis de Canales iónicos de la musculatura Lisa arterial y su Explotación terapéutica Sistemática) fue calificada con mención Excelente en la evaluación de 2005, y se ha consolidado con la incorporación de nuevos grupos en la convocatoria 2007. Las actividades de la red se enmarcan en la transferencia de conocimiento del bedside-to-bench, así como su inversa, bench-to-bedside. Los objetivos actuales de la red son: a) estudio de canales de K+ dependientes de Ca2+, canales catiónicos TRP y canales de Cl- dependientes de Ca2+ que participan en la fisiología vascular; b) estudio de los mapas de expresión proteínica en plasma y tejido cardiovascular y su relevancia en el tratamiento farmacológico; c) estudios del efecto de los flavonoides en el transporte iónico y la respuesta al estrés oxidativo, y d) identificación de marcadores biológicos de riesgo, pronóstico y respuesta al tratamiento en fenotipos de HTA extremos. Nuestro proyecto incluye un conjunto de líneas de investigación coordinadas con programas horizontales basados en plataformas centrales, que las sirven. La red ha publicado más de 60 manuscritos (disponibles en: http://www.redheracles.net) y ha recibido financiación para más de 90 proyectos en convocatorias competitivas nacionales y 6 internacionales, y un Biobanco ADN (AU)


In 2002, a group of researchers in the fields of cell electrophysiology, cardiology, population genetics, epidemiology, proteomics, molecular biology, bioinformatics and statistics decided to take up the challenge of investigating the mechanisms and genetics of arterial hypertension (AH). Mechanisms related to ion channel regulation of arterial smooth muscle function were identified. The HERACLES (Hipertensión Esencial: Red de Análisis de Canales iónicos de la musculatura Lisa arterial y su Explotación terapéutica Sistemática) network was honored with a distinguished mention in the 2005 evaluation, and was strengthened by the incorporation of new research groups in 2007. The work of the HERACLES network is characterized as much by the transfer of knowledge «from bedside to bench» as by its converse: «from bench to bedside». The current objectives of the HERACLES network are: a) to study the Ca2+-dependent K+ channels, the transient receptor potential (TRP) cation channels, and the Ca2+-dependent Cl- channels that are involved in vascular physiology; b) to study protein expression maps in plasma and cardiovascular tissue and their significance for drug treatment; c) to study the effect of flavonoids onion transport and responses to oxidative stress, and d) to identify biomarkers of risk, prognosis, and treatment responses in extreme AH phenotypes. Our project includes a number of lines of research coordinated within cross-sectional programs based on centralized facilities, which are used by them. The HERACLES network has published more than 60 articles (available from: http://www.redheracles.net), funding has been received for more than 90 projects in competitive submissions to Spanish and six international bodies, and there is a DNA Biobank (AU)


Assuntos
Humanos , Técnicas Eletrofisiológicas Cardíacas/tendências , Pesquisa Biomédica/tendências , Canais Iônicos , Hipertensão/fisiopatologia , Apoio à Pesquisa como Assunto , Doenças Cardiovasculares/diagnóstico , Comportamento Cooperativo
16.
J. physiol. biochem ; 63(4): 317-328, oct.-dic. 2007. ilus, tab, graf
Artigo em Inglês | IBECS | ID: ibc-76686

RESUMO

The aim of the present work was to assess whether changes in adipose tissue geneexpression related with adipogenesis and/or thermogenesis could be involved in themechanism conferring susceptibility or resistance to develop obesity in high-fat fedoutbreed rats. For this purpose, male Wistar rats were fed with standard laboratorydiet (control group) or high fat diet. After 15 days, two groups of rats with significantdifferences on body weight gain in response to the high fat diet were characterizedand identified as diet-induced obesity (DIO) and diet resistant (DR) rats. A significantincrease in visceral white adipose tissue (WAT) PPARã and aP2 (p<0.05)mRNA levels associated to a decrease in RARã expression (p<0.05) was observed inDIO rats, suggesting an increase of adipogenesis. Furthermore, our data showed amarked increase in brown adipose tissue (BAT) of UCP1 mRNA in DIO animals(p<0.01) (without affecting PGC-1á gene expression), whereas no changes werefound in WAT UCP2 gene expression. All these data suggest that the variationsfound in the expression pattern of PPARã, aP2 and RARã by high-fat diet could beinvolved, at least in part, in the differences in body weight gain and adiposityobserved between DR and DIO animals. The compensatory adaptations through theincrease in energy expenditure by changes on the expression levels of UCP1 seem notto be enough to avoid the obesity onset in the DIO group (AU)


No disponible


Assuntos
Animais , Ratos , Adipogenia/genética , Tecido Adiposo/metabolismo , Gorduras na Dieta/administração & dosagem , Obesidade/genética , Termogênese/genética , Fatores de Transcrição/genética , Proteínas de Ligação a RNA/genética , Predisposição Genética para Doença/genética , Canais Iônicos/genética , Proteínas Mitocondriais/genética , Peso Corporal/genética
19.
Rev. neurol. (Ed. impr.) ; 39(7): 668-681, 1 oct., 2004.
Artigo em Es | IBECS | ID: ibc-36314

RESUMO

Se realiza una somera exposición de los diferentes planteamientos y doctrinas que se han ido desarrollando a lo largo de la historia de la medicina occidental con la intención de ofrecer una visión de conjunto. El autor cree que los hechos más importantes desde el punto de vista conceptual se centran en la noción de localización cerebral de las funciones psíquicas en la obra de F. Gall; la elaboración de la noción de centros nerviosos debida a Fritsch y Hitzig que posibilitó el espléndido trabajo de D. Ferrier, verdadero creador de la neuropsicología científica; el trabajo de Klest, que supone un nuevo neogallismo en el sentido de representar un verdadero esfuerzo de localización de funciones psíquicas superiores; el trabajo fundamental de J.H. Jackson, especialmente en relación con el tema que estudiamos, sus ideas sobre los niveles de función e integración del sistema nervioso, que permitió los desarrollos posteriores, entre otros el de MacLean, cuyo concepto del sistema límbico es central en este tema; la crítica de la noción de centro nervioso que realizó W.H. Hess y la de función de A.R. Luria, necesaria para poder entender los modelos neuropsicológicos actuales, y, finalmente, el desarrollo de las ideas sobre la especialización del sistema nervioso (AU)


In this work we outline the different approaches and doctrines that have been successively developed throughout the history of western medicine with the intention of offering an overall view of the matter. The author believes that the most important facts from a conceptual point of view are centred around F. Gall’s notion of the cerebral localisation of the psychic functions; the development of the notion of nerve centres put forward by Fritsch and Hitzig, which was the foundation for the splendid work of D. Ferrier, the true father of scientific neuropsychology; the work of Klest, which gave rise to a new neogallism in the sense that it represented a real effort to locate the higher psychic functions; the fundamental work of J.H. Jackson, especially in relation to the subject we are studying, and his ideas about the levels of functioning and integration of the nervous system, which enabled later developments to be carried out, such as that of MacLean, whose concept of the limbic system is a core matter in this area. Other milestones were W.H. Hess’s critique of the notion of nerve centre and that of function by A.R. Luria, which is necessary to be able to understand the modern-day neuropsychological models, and finally the development of the ideas about the specialisation of the nervous system (AU)


Assuntos
Humanos , Canais Iônicos , Canais de Sódio , Proteínas Serina-Treonina Quinases , Paralisia Periódica Hiperpotassêmica , Distrofia Miotônica , Proteínas Musculares , Expansão das Repetições de Trinucleotídeos , Frequência do Gene , Cromossomos Humanos Par 19 , Canais de Cloreto , Idade de Início , Regiões 3' não Traduzidas , Transtornos Miotônicos , Proteínas de Ligação a RNA
20.
Rev. neurol. (Ed. impr.) ; 38(7): 668-674, 1 abr., 2004.
Artigo em Es | IBECS | ID: ibc-31467

RESUMO

Objetivo. Revisar los aspectos genéticos y moleculares de las miotonías distróficas y no distróficas. Desarrollo. Las enfermedades miotónicas son condiciones hereditarias del músculo esquelético, las cuales se pueden clasificar en dos grupos según el cuadro clínico. Al primer grupo pertenecen las miotonías distróficas, donde se encuentran las distrofias miotónicas (DM) tipo 1 y 2.Al segundo grupo pertenecen las canalopatías, que se caracterizan por presentar alteraciones de la función en los canales iónicos. La DM tipo 1, enfermedad neurodegenerativa, progresiva y discapacitante, la causa una expansión del trinucleótido CTG, cuyo tamaño muestra correlación positiva con la gravedad y negativa con la edad de manifestación. Existe evidencia suficiente para pensar que el mecanismo fisiopatológico de la enfermedad es la ganancia de función del ARN mutado. La DM tipo 2, menos grave que la tipo 1, la causa una expansión del tetranucleótido CCTG, cuyo mecanismo fisiopatológico es similar al propuesto para la tipo 1. En el segundo grupo se encuentran las canalopatías de cloruro, de herencia autosómica dominante o recesiva, causadas por una de las 60 diferentes mutaciones en el gen del canal de cloruro, y las canalopatías de sodio, grupo de tres enfermedades que se solapan clínicamente, de herencia dominante, causadas por una de las 25 diferentes mutaciones en el gen del canal de sodio. Conclusiones. Estas enfermedades son clínicamente muy variables; no obstante, su base genética se conoce; falta todavía mucha investigación para lograr entender su fisiopatología y las relaciones genotipo-fenotipo (AU)


Assuntos
Humanos , Proteínas Musculares , Transtornos Miotônicos , Expansão das Repetições de Trinucleotídeos , Canais de Sódio , Proteínas Serina-Treonina Quinases , Paralisia Periódica Hiperpotassêmica , Canais Iônicos , Frequência do Gene , Distrofia Miotônica , Regiões 3' não Traduzidas , Canais de Cloreto , Cromossomos Humanos Par 19 , Idade de Início , Frequência do Gene , Proteínas de Ligação a RNA
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