RESUMEN
El objetivo de este estudio es elaborar un perfil de percepciones, emociones y opiniones en torno a experiencias de apego de un grupo de madres de niños con retraso madurativo, a través del análisis de contenido de un foro virtual. A partir de los datos se extraen tres dimensiones de análisis: sistema de conductas del niño, sistema de cuidados y crianza mediada por profesionales. Los resultados permiten detectar como temas recurrentes de preocupación en las madres los siguientes: incertidumbre por el diagnóstico; dificultades para interpretar la conducta de sus hijos y responder consecuentemente; búsqueda de intimidad afectiva, y predominio del aprendizaje guiado durante las primeras etapas del diagnóstico. Se concluye que la categoría retraso madurativo, al ser provisional, dificulta el proceso de aceptación, lo cual impacta negativamente en el sistema de cuidados materno. Al respecto, la terminología, actitudes y prácticas de los profesionales de apoyo parecen jugar un papel importante. El deseo de lograr intimidad afectiva, las emociones positivas y un adecuado acompañamiento profesional serían factores protectores para establecer vínculos de apego más favorables entre las figuras parentales y sus hijos
The aim of this study is to develop a profile of attachment experienc¬es through the analysis of content shared in a virtual forum by a group of mothers who have children with developmental delay. Three categories were extracted from the data: behavioural system, care system, and professional parenting assistance. The results allowed the identification of the mothers' emotional states associated with the uncer¬tainty about diagnosis, difficulty interpreting their children behaviour, and responding consequently, seeking emotional intimacy, and prevalence of guided learning during the early stages of diagnosis. It is concluded that the diagnosis "developmental delay", being provisional, makes the acceptance process difficult, which impacts the maternal care system negatively. Terminology, attitudes, and practices of support professionals seem to play an important role. The desire for emotional intimacy, positive emotions, and appropriate professional support would be protective factors to establish a more favourable attachment between parents and children
Asunto(s)
Humanos , Masculino , Femenino , Lactante , Preescolar , Niño , Adulto Joven , Adulto , Madres/psicología , Relaciones Madre-Hijo/psicología , Discapacidad Intelectual/psicología , 25783RESUMEN
Neurotoxic effects of amyloid ß peptides are mediated through deregulation of intracellular Ca(2+) homeostasis and signaling, but relatively little is known about amyloid ß modulation of Ca(2+) homeostasis and its pathological influence on glia. Here, we found that amyloid ß oligomers caused a cytoplasmic Ca(2+) increase in cultured astrocytes, which was reduced by inhibitors of PLC and ER Ca(2+) release. Furthermore, amyloid ß peptides triggered increased expression of glial fibrillary acidic protein (GFAP), as well as oxidative and ER stress, as indicated by eIF2α phosphorylation and overexpression of chaperone GRP78. These effects were decreased by ryanodine and 2APB, inhibitors of ryanodine receptors and InsP3 receptors, respectively, in both primary cultured astrocytes and organotypic cultures of hippocampus and entorhinal cortex. Importantly, intracerebroventricular injection of amyloid ß oligomers triggered overexpression of GFAP and GRP78 in astrocytes of the hippocampal dentate gyrus. These data were validated in a triple-transgenic mouse model of Alzheimer's disease (AD). Overexpression of GFAP and GRP78 in the hippocampal astrocytes correlated with the amyloid ß oligomer load in 12-month-old mice, suggesting that this parameter drives astrocytic ER stress and astrogliosis in vivo. Together, these results provide evidence that amyloid ß oligomers disrupt ER Ca(2+) homeostasis, which induces ER stress that leads to astrogliosis; this mechanism may be relevant to AD pathophysiology.
Asunto(s)
Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/farmacología , Astrocitos/metabolismo , Calcio/metabolismo , Estrés del Retículo Endoplásmico/efectos de los fármacos , Gliosis/metabolismo , Factores de Edad , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/patología , Animales , Astrocitos/efectos de los fármacos , Astrocitos/patología , Modelos Animales de Enfermedad , Retículo Endoplásmico/efectos de los fármacos , Retículo Endoplásmico/metabolismo , Chaperón BiP del Retículo Endoplásmico , Corteza Entorrinal/efectos de los fármacos , Corteza Entorrinal/metabolismo , Corteza Entorrinal/patología , Expresión Génica/efectos de los fármacos , Proteína Ácida Fibrilar de la Glía , Gliosis/genética , Gliosis/patología , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Hipocampo/patología , Humanos , Receptores de Inositol 1,4,5-Trifosfato/genética , Receptores de Inositol 1,4,5-Trifosfato/metabolismo , Ratones , Ratones Transgénicos , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Cultivo Primario de Células , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Canal Liberador de Calcio Receptor de Rianodina/genética , Canal Liberador de Calcio Receptor de Rianodina/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
Much of the cell death following episodes of anoxia and ischemia in the mammalian central nervous system has been attributed to extracellular accumulation of glutamate and ATP, which causes a rise in [Ca(2+)](i), loss of mitochondrial potential, and cell death. However, restoration of blood flow and reoxygenation are frequently associated with exacerbation of tissue injury (the oxygen paradox). Herein we describe a novel signaling pathway that is activated during ischemia-like conditions (oxygen and glucose deprivation; OGD) and contributes to ischemia-induced oligodendroglial cell death. OGD induced a retarded and sustained increase in extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation after restoring glucose and O(2) (reperfusion-like conditions). Blocking the ERK1/2 pathway with the MEK inhibitor UO126 largely protected oligodendrocytes against ischemic insults. ERK1/2 activation was blocked by the high-affinity Zn(2+) chelator TPEN, but not by antagonists of AMPA/kainate or P2X7 receptors that were previously shown to be involved in ischemic oligodendroglial cell death. Using a high-affinity Zn(2+) probe, we showed that ischemia induced an intracellular Zn(2+) rise in oligodendrocytes, and that incubation with TPEN prevented mitochondrial depolarization and ROS generation after ischemia. Accordingly, exposure to TPEN and the antioxidant Trolox reduced ischemia-induced oligodendrocyte death. Moreover, UO126 blocked the ischemia-induced increase in poly-[ADP]-ribosylation of proteins, and the poly[ADP]-ribose polymerase 1 (PARP-1) inhibitor DPQ significantly inhibited ischemia-induced oligodendroglial cell death-demonstrating that PARP-1 was required downstream in the Zn(2+)-ERK oligodendrocyte cell death pathway. Chelation of cytosolic Zn(2+), blocking ERK signaling, and antioxidants may be beneficial for treating CNS white matter ischemia-reperfusion injury. Importantly, all the inhibitors of this pathway protected oligodendrocytes when applied after the ischemic insult.
Asunto(s)
Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Glucosa/metabolismo , Hipoxia/metabolismo , Oligodendroglía/metabolismo , Poli(ADP-Ribosa) Polimerasas/metabolismo , Daño por Reperfusión/metabolismo , Zinc/metabolismo , Animales , Calcio/metabolismo , Potencial de la Membrana Mitocondrial/fisiología , Oligodendroglía/patología , Fosforilación , Poli(ADP-Ribosa) Polimerasa-1 , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Daño por Reperfusión/patologíaRESUMEN
Introducción. Se describe la presencia de violencia de género en mujeres con ascendencia étnica aymara, analizando la presencia de diferencias con mujeres de ascendencia no originaria. Material y métodos. Participaron 400 mujeres residentes en la región de Arica y Parinacota-Chile. Se utilizó la versión en español de las escalas Index of Spouse Abuse (ISA) y Woman Abuse Screening Tool (WAST). Resultados. Los resultados evidencian un predominio de violencia no física hacia la mujer en la relación de pareja, hallando diferencias significativas entre las participantes en función de la ascendencia étnica, siendo mayores los índices de violencia en las mujeres con ascendencia aymara. Conclusiones. Se concluye que las construcciones sociales respecto al género presentes en la cultura aymara constituyen un factor de riesgo para la violencia de género, debido a su influencia en la emergencia de asimetrías sociales y condiciones de abuso de poder hacia la mujer(AU)
Introduction. We analyze the gender-based violence against women considering the Aymara ethnic ascendance as a casual factor. Material and methods. We applied the spanish version of the Index of Spouse Abuse Scales (ISA) and Woman Abuse Screening Tool (WAST) on 400 women, which currently live in the region of Arica and Parinacota, Chile. Results. The individuals show that non-physical violence is the predominant behavior in couples and higher rate of violence is present in women with Aymara ancestry than others. Conclusions. We conclude that social constructions of gender may be a risk factor in violence against women because of its influence in social inequalities and abuses of power against women(AU)
Asunto(s)
Humanos , Femenino , Adulto , Violencia Doméstica/psicología , Violencia Doméstica/estadística & datos numéricos , Violencia contra la Mujer , Etnicidad/psicología , Factores de Riesgo , Psicometría/métodos , Violencia Doméstica/etnología , Chile/epidemiología , Maltrato Conyugal/etnología , Maltrato Conyugal/psicología , Conflicto Familiar/psicología , Psicometría/tendencias , Modelos LogísticosRESUMEN
INTRODUCTION: We analyze the gender-based violence against women considering the Aymara ethnic ascendance as a casual factor. MATERIAL AND METHODS: We applied the spanish version of the Index of Spouse Abuse Scales (ISA) and Woman Abuse Screening Tool (WAST) on 400 women, which currently live in the region of Arica and Parinacota, Chile. RESULTS: The individuals show that non-physical violence is the predominant behavior in couples and higher rate of violence is present in women with Aymara ancestry than others. CONCLUSIONS: We conclude that social constructions of gender may be a risk factor in violence against women because of its influence in social inequalities and abuses of power against women.
Asunto(s)
Indígenas Sudamericanos , Relaciones Interpersonales , Violencia/estadística & datos numéricos , Adulto , Chile , Femenino , HumanosRESUMEN
A growing number of studies have demonstrated an association between serum levels of insulin-like growth factors (IGFs) and IGF binding protein-3 (IGFBP-3) and increased risk for various cancers. The aim of this study was to evaluate the relationship between levels of IGF-II or IGFBP-3 in cervical scrapes with cervical cancer and precancerous lesions: low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion (HSIL). 4 groups of cases were examined: LSIL (n=20), HSIL (n=28), cervical cancer (n=45), and controls (n=51). Control subjects were women with normal, HPV DNA-negative Papanicolau (Pap) test. IGF-II and IGFBP-3 levels in cervical scrapes were measured by ELISA. Results show that median protein levels of IGF-II were significantly lower in cervical cancer cases vs. controls (446.5 ng/mg vs. 1,168.6 ng/mg, p<0.001). Significantly higher values of IGFBP-3 were found in HSIL vs. controls (median: 549.5 ng/mg vs. 216 ng/mg; p=0.018), and were not affected by HR HPV infection, meanwhile no significant differences were observed in IGFBP-3 levels between LSIL or cervical cancer as compared to controls. These data suggests that the progression to cervical cancer is associated with alterations in the IGF system and not affected by HR HPV infection. More studies are needed to understand the possible role of IGFBP-3 in cervical carcinogenesis.
Asunto(s)
Cuello del Útero/patología , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Factor II del Crecimiento Similar a la Insulina/metabolismo , Neoplasias de Células Escamosas/metabolismo , Displasia del Cuello del Útero/metabolismo , Neoplasias del Cuello Uterino/metabolismo , Adulto , Cuello del Útero/metabolismo , Femenino , Humanos , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias de Células Escamosas/patología , Neoplasias del Cuello Uterino/patología , Frotis Vaginal , Displasia del Cuello del Útero/patologíaRESUMEN
Amyloid beta (Abeta) oligomers accumulate in brain tissue of Alzheimer disease patients and are related to pathogenesis. The precise mechanisms by which Abeta oligomers cause neurotoxicity remain unresolved. In this study, we investigated the role of ionotropic glutamate receptors on the intracellular Ca2+ overload caused by Abeta. Using rat cortical neurons in culture and entorhinal-hippocampal organotypic slices, we found that Abeta oligomers significantly induced inward currents, intracellular Ca2+ increases and apoptotic cell death through a mechanism requiring NMDA and AMPA receptor activation. The massive entry of Ca2+ through NMDA and AMPA receptors induced by Abeta oligomers caused mitochondrial dysfunction as indicated by mitochondrial Ca2+ overload, oxidative stress and mitochondrial membrane depolarization. Importantly, chronic treatment with nanomolar concentration of Abeta oligomers also induced NMDA- and AMPA receptor-dependent cell death in entorhinal cortex and hippocampal slice cultures. Together, these results indicate that overactivation of NMDA and AMPA receptor, mitochondrial Ca2+ overload and mitochondrial damage underlie the neurotoxicity induced by Abeta oligomers. Hence, drugs that modulate these events can prevent from Abeta damage to neurons in Alzheimer's disease.
Asunto(s)
Péptidos beta-Amiloides/metabolismo , Señalización del Calcio/fisiología , Calcio/metabolismo , Degeneración Nerviosa/metabolismo , Receptores de Glutamato/metabolismo , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/fisiopatología , Péptidos beta-Amiloides/toxicidad , Animales , Apoptosis/fisiología , Señalización del Calcio/efectos de los fármacos , Células Cultivadas , Metabolismo Energético/fisiología , Corteza Entorrinal/metabolismo , Hipocampo/metabolismo , Potencial de la Membrana Mitocondrial/fisiología , Mitocondrias/metabolismo , Degeneración Nerviosa/inducido químicamente , Degeneración Nerviosa/fisiopatología , Técnicas de Cultivo de Órganos , Estrés Oxidativo/fisiología , Ratas , Ratas Sprague-Dawley , Receptores AMPA/metabolismo , Receptores de Glutamato/efectos de los fármacos , Receptores de N-Metil-D-Aspartato/metabolismoRESUMEN
Human papillomavirus (HPV) is the main risk factor for cervical cancer; however, some carcinomas occur in the absence of the virus. IGF-IR and an isoform of the insulin receptor, IR-A, play important roles in cancer. In this study we assessed the role of the IGF/insulin receptors in cervical cancer cell lines with different HPV status, SiHa (HPV positive), and C33a (HPV negative). Different patterns of receptor expression were found; while SiHa expressed IGF-IR, IR-A and IR-B, and IR/IGF-IR hybrid receptors, C33a cells expressed the IR-A only. Tyrosine phosphorylation of these receptors in response to their corresponding ligands correlated with the expression level of these receptors in the cell lines. Activation of PI3-K and MAPK pathways was revealed in both cell lines, however, no effects on proliferation, migration, or invasion were observed. Here we show that cervical cancer cell lines--positive and negative for HPV--differ in the type of insulin and IGF-1 receptors expressed. Additional studies are needed for characterization of the role of IR-A in cervical carcinogenesis.
Asunto(s)
Papillomaviridae/fisiología , Receptor IGF Tipo 1/metabolismo , Receptor de Insulina/metabolismo , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/virología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Activación Enzimática/efectos de los fármacos , Femenino , Humanos , Factor I del Crecimiento Similar a la Insulina/farmacología , Factor II del Crecimiento Similar a la Insulina/farmacología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Isoformas de Proteínas/metabolismo , Neoplasias del Cuello Uterino/enzimología , Neoplasias del Cuello Uterino/patologíaRESUMEN
Choriocarcinoma is a highly malignant tumor that can arise from trophoblasts of any type of gestational event but most often from complete hydatidiform mole. IGF-II plays a fundamental role in placental development and may play a role in gestational trophoblastic diseases. Several studies have shown that IGF-II is expressed at high levels in hydatidiform moles and choriocarcinoma tissues; however, conflicting data exist on how IGF-II regulates the behaviour of choriocarcinoma cells. The purpose of this study was to determine the contribution of the receptors for IGF-I and insulin to the actions of IGF-II on the regulation of choriocarcinoma cells metastasis. An Immuno Radio Metric Assay was used to analyse the circulating and tissue levels of IGF-I and IGF-II in 24 cases of hydatidiform mole, two cases of choriocarcinoma and eight cases of spontaneous abortion at the same gestational age. The JEG-3 choriocarcinoma cell line was used to investigate the role of IGF-II in the regulation of cell invasion. We found that mole and choriocarcinoma tissue express high levels of IGF-II compared to first trimester placenta. Both IGF-I and IGF-II regulate choriocarcinoma cell invasion in a dose dependent manner but through a different mechanism. IGF-II effects involve the activation of the InsR while IGF-I uses the IGF-IR. The positive effects of IGF-II on invasion are the result of enhanced cell adhesion and chemotaxis (specifically towards collagen IV). The actions of IGF-II but not those of IGF-I were sensitive to inhibition by the insulin receptor inhibitor HNMPA(AM)3. Our results demonstrate that the insulin receptor regulates choriocarcinoma cell invasion.
Asunto(s)
Antígenos CD/metabolismo , Coriocarcinoma/secundario , Factor II del Crecimiento Similar a la Insulina/fisiología , Receptor de Insulina/metabolismo , Neoplasias Uterinas/patología , Adulto , Adhesión Celular , Línea Celular Tumoral , Movimiento Celular , Coriocarcinoma/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Femenino , Humanos , Factor I del Crecimiento Similar a la Insulina/análisis , Factor I del Crecimiento Similar a la Insulina/farmacología , Factor I del Crecimiento Similar a la Insulina/fisiología , Factor II del Crecimiento Similar a la Insulina/análisis , Factor II del Crecimiento Similar a la Insulina/farmacología , Naftalenos/farmacología , Organofosfonatos/farmacología , Embarazo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptor IGF Tipo 1/metabolismo , Receptor de Insulina/agonistas , Neoplasias Uterinas/metabolismoRESUMEN
Constipation has an effect in traumatology and orthopedic surgery as a real and potential problem capable of increasing disease-caused mortality related to the slowness of feces in the intestinal tract; furthermore, constipation contributes manifestly to an alteration in a patient's well-being. In spite of this, there are very few studies in this area of knowledge in nursing and the majority of cases, constipation is considered to be a secondary problem among general treatment plans for trauma patients' linked to a syndrome of disuse due to being bedridden. In this study, the authors have tried to point out the magnitude and the clinical importance constipation has in trauma ward patients as well as create a treatment protocol which has some specific treatments which permit a standardization of nursing care provided to at risk patients. To develop this, the authors have carried out a comparative study following the directions established by the Process of Nursing Treatment as the paradigm for the application of the scientific method in professional practice. The evaluation of the results obtained in this study let the authors conclude that the adoption of this standardized protocol which we present for treatment of constipation suffered by trauma ward patients improves the pattern of bowel movements by patients hospitalized with fractures in their inferior extremities without having backbone complications.
Asunto(s)
Estreñimiento/enfermería , Complicaciones Posoperatorias/enfermería , Adulto , Anciano , Protocolos Clínicos , Estreñimiento/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/diagnóstico , Estudios ProspectivosRESUMEN
El estreñimiento se revela en el área de la cirugía ortopédica y traumatológica (COT) como un problema potencial y real capaz de aumentar la morbimortalidad relacionada con el enlentecimiento de las heces en el tracto intestinal; además de contribuir manifiestamente a la alteración del bienestar del usuario. A pesar de ello, apenas existen trabajos al respecto en el área de conocimientos de la enfermería y en la mayor parte de los casos se contempla como un problema secundario dentro de planes generales del cuidado de los pacientes traumatizados asociado al síndrome de desuso por encamamiento. Hemos intentado con este trabajo poner de relieve la magnitud e importancia clínica del estreñimiento en la COT así como la creación de un protocolo de cuidados específico que permita estandarizar la atención de enfermería ofrecida a los usuarios en riesgo. Para su confección, se ha realizado un estudio comparativo en el que hemos seguido el eje directriz establecido por el PAE (Proceso de Atención de Enfermería) como paradigma de la aplicación del método científico a la práctica profesional. La evaluación de los resultados obtenidos en dicho estudio nos permite concluir que la adopción del protocolo estandarizado que planteamos para el cuidado del estreñimiento en COT mejora el patrón de eliminación intestinal hospitalario de los pacientes con fracturas de las extremidades inferiores sin afectación vertebral. Primer premio de Calidad en cuidados de enfermería, del Complejo Hospitalario Universitario de Santiago de Compostela (AU)
Asunto(s)
Adulto , Femenino , Masculino , Persona de Mediana Edad , Humanos , Atención de Enfermería/métodos , Procedimientos Ortopédicos/efectos adversos , Estreñimiento/enfermería , Protocolos Clínicos , Ortopedia , Calidad de la Atención de Salud , Diagnóstico de Enfermería , Pierna , Traumatismos de la Pierna/enfermería , Estreñimiento/etiologíaRESUMEN
A role for neuropeptide receptors in glial tumorigenesis has recently been proposed. Although angiotensin receptors are known to mediate proliferative effects in many cell types, including brain astrocytes, the possible participation of these receptors in glial tumorigenesis remains unknown. In the present study, we have examined the expression of the molecularly defined angiotensin receptor subtypes AT(1a), AT(1b), and AT(2) in normal perinatal rat astrocytes and in a panel of tumor adult astrocytoma cells, using the reverse transcriptase-polymerase chain reaction (RT-PCR). Subsequently, we compared the mitogenic effect of the angiotensins A(1-8), A(2-8), A(3-8) and the heptapeptide "metabolite" A(1-7), on both normal and tumor astrocytes, measured in terms of the incorporation of tritiated thymidine. Our results indicate that AT(1a), AT(1b), and AT(2) angiotensin receptor mRNA is commonly expressed by many of these cells. Of notable exception is the astrocytoma U373 which was not found to express AT(1) or AT(2) mRNA. Chronic (24-h) incubation of cells with A(1-8) and A(1-7) lead to the induction of mitogenesis, even in the AT(1) and AT(2) mRNA negative astrocytoma cell line U373. Moreover, pharmacological analysis indicated that the observed mitogenic effects are not mediated by the AT(1) or AT(2) type receptors, but rather by a novel, specific A((1-7)) angiotensin receptor, since mitogenesis was shown to be partially blocked by the A(1-7) analogue D-Ala(7)A(1-7) and by the protease inhibitor orthophenanthroline (100 microM). Using Fura-2 spectrophotometry, we found that activation of this receptor does not alter intracellular calcium levels; however, preincubation with the protein kinase kinase inhibitor U0126 (10 microM) was found to inhibit these mitogenic effects partially. Overall, these results which demonstrate that normal and tumor astrocytes express a greater variety of angiotensin receptor subtypes than previously thought, support the idea that A(1-7) and its receptor signaling system may play an important role in shaping the astrocyte population during development. Moreover, the untimely expression of this A((1-7)) receptor may represent an important etiological component in the development of brain astrocytomas.
Asunto(s)
Astrocitos/metabolismo , Astrocitoma/metabolismo , Receptores de Angiotensina/biosíntesis , Receptores de Angiotensina/clasificación , Angiotensinas/farmacología , Angiotensinas/fisiología , Animales , Animales Recién Nacidos , Astrocitos/citología , Células Cultivadas , Corteza Cerebral/citología , Corteza Cerebral/metabolismo , Relación Dosis-Respuesta a Droga , Humanos , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , ARN Mensajero/biosíntesis , Ratas , Receptor de Angiotensina Tipo 1 , Receptor de Angiotensina Tipo 2 , Células Tumorales CultivadasRESUMEN
En la consulta diaria de atención primaria, ante un paciente hipertenso no controlado, diversos factores pueden influir en su control, entre los que se incluyen la efectividad del tratamiento, la observancia que el paciente realiza del mismo y la utilización por indicación del m édico o del propio paciente de fármacos capaces de provocar potenciales interacciones con los antihipertensivos o de elevar per se la presión arterial. Tras la realización de nuestro estudio, podemos concluir que este último factor no es irrelevante y que aparece en una proporción superior a lo previsible, por lo que no se debe subestimar (AU)
Asunto(s)
Humanos , Atención Primaria de Salud , Antihipertensivos/uso terapéutico , Interacciones Farmacológicas , Diuréticos , Antagonistas Adrenérgicos beta , Inhibidores de la Enzima Convertidora de Angiotensina , Receptores de Angiotensina/antagonistas & inhibidores , Angiotensinógeno , Hipertensión/tratamiento farmacológicoRESUMEN
Oligodendrocytes, the myelinating cells of CNS axons, are highly vulnerable to excitotoxic signals mediated by glutamate receptors of the AMPA and kainate classes. Receptors in these cells are commonly activated by glutamate that is released from axons and glial cells. In addition, oligodendrocytes contribute to the control of extracellular glutamate levels by means of their own transporters. However, acute and chronic alterations in glutamate homeostasis can result in overactivation of AMPA and kainate receptors and subsequent excitotoxic oligodendroglial death. Furthermore, demyelinating lesions caused by excitotoxins can be similar to those observed in multiple sclerosis. This, together with the effect of AMPA and kainate receptor antagonists in ameliorating the neurological score of animals with experimental autoimmune encephalomyelitis (an animal model of multiple sclerosis), indicates that oligodendrocyte excitotoxicity could be involved in the pathogenesis of demyelinating disorders.
Asunto(s)
Autoinmunidad/fisiología , Enfermedades Desmielinizantes/metabolismo , Ácido Glutámico/metabolismo , Esclerosis Múltiple/metabolismo , Neurotoxinas/metabolismo , Oligodendroglía/metabolismo , Animales , Autoinmunidad/efectos de los fármacos , Muerte Celular/efectos de los fármacos , Muerte Celular/fisiología , Enfermedades Desmielinizantes/tratamiento farmacológico , Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Encefalomielitis Autoinmune Experimental/metabolismo , Encefalomielitis Autoinmune Experimental/patología , Humanos , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/patología , Neurotoxinas/antagonistas & inhibidores , Oligodendroglía/efectos de los fármacos , Nervio Óptico/efectos de los fármacos , Nervio Óptico/patología , Receptores AMPA/antagonistas & inhibidores , Receptores AMPA/metabolismo , Receptores de Ácido Kaínico/antagonistas & inhibidores , Receptores de Ácido Kaínico/metabolismo , Receptor de Ácido Kaínico GluK2RESUMEN
In this study we describe the development of a RNA:RNA solution hybridization-RNase protection assay to quantify STAT5 mRNA in total RNA extracts from rat tissues. The assay is sensitive and reproducible. We quantified STAT5 mRNA levels in liver and thymus lymphocytes from male and female control rats and from rats treated with a single dose of recombinant human growth hormone (rhGH). No significant sex differences in the expression pattern were observed in both studied tissues, but STAT5 mRNA levels were significantly (P< 0.05) higher in liver than in thymus lymphocytes. STAT5 mRNA levels were significantly (P< 0.05) increased by a pulse of GH given to either male or female normal rats, suggesting a regulation of STAT5 gene expression in the studied tissues. In conclusion, quantitative solution hybridization-RNase protection assay of STAT5 mRNA provides a tool to further advance the study of the regulatory mechanisms involved in STAT5 gene expression.
Asunto(s)
Proteínas de Unión al ADN/genética , Hormona de Crecimiento Humana/farmacología , Hígado/metabolismo , Proteínas de la Leche , ARN Mensajero/análisis , Linfocitos T/metabolismo , Transactivadores/genética , Transcripción Genética/efectos de los fármacos , Animales , Femenino , Humanos , Masculino , Hibridación de Ácido Nucleico/métodos , ARN Mensajero/genética , Ratas , Ratas Wistar , Ribonucleasas , Factor de Transcripción STAT5 , Sensibilidad y Especificidad , Caracteres Sexuales , Timo/metabolismoRESUMEN
Recent studies indicate that oligodendrocytes are vulnerable to excitotoxic insults mediated by glutamate receptors. The present study was carried out to characterize the type of glutamate receptors triggering cell death in optic nerve oligodendrocyte cultures. Acute activation of either AMPA or kainate receptors was toxic to oligodendrocytes, an effect that was prevented by CNQX. However, exposure to agonists of the NMDA and metabotropic glutamate receptors did not impair cell viability. Dose-response curves showed that toxicity was mediated by three distinct populations of receptors: an AMPA-type receptor and high- and low-affinity kainate-type receptors. Expression and immunocytochemical studies suggested that the glutamate receptor subunits give rise to the native receptors in each population. In all instances, Ca(2+) entry was a major determinant of glutamate receptor excitotoxicity. However, its influence varied for each receptor subtype. These results indicate that aberrantly enhanced activation of AMPA and/or kainate receptors may be involved in demyelinating diseases.
Asunto(s)
Neurotoxinas/farmacología , Oligodendroglía/efectos de los fármacos , Receptores AMPA/efectos de los fármacos , Receptores AMPA/metabolismo , Receptores de Ácido Kaínico/efectos de los fármacos , Receptores de Ácido Kaínico/metabolismo , Animales , Animales Recién Nacidos , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Calcio/metabolismo , Células Cultivadas/efectos de los fármacos , Células Cultivadas/metabolismo , Agonistas de Aminoácidos Excitadores/farmacología , Antagonistas de Aminoácidos Excitadores/farmacología , Ácido Glutámico/farmacología , Oligodendroglía/citología , Oligodendroglía/metabolismo , Nervio Óptico/citología , Nervio Óptico/efectos de los fármacos , Nervio Óptico/metabolismo , Ratas , Ratas Sprague-Dawley , Sodio/metabolismoRESUMEN
The aim of the present study was to investigate the influence of dietary protein level on the protein anabolic effects of growth hormone (GH) and insulin-like growth factor-I (IGF-I). Female growing rats were fed on either a high- or a low-protein diet with crude protein contents of 222 and 83 g/kg respectively. The diets contained the same amount of metabolizable energy (15.1 MJ/kg) and were given during a 14 d period. During the same time, three groups of rats (n 8) on each diet received subcutaneous infusions of either saline, recombinant human GH (rhGH) or recombinant human IGF-I (rhIGF-I). rhGH and rhIGF-I were given in doses of 360 and 500 micrograms/d respectively. The low-protein diet alone reduced significantly (P < 0.05) IGF-I concentrations in serum and in tissue taken from the gastrocnemius muscle as well as IGF-I mRNA from the same muscle. The responses to rhGH and rhIGF-I in terms of muscle IGF-I and its mRNA were variable. However, when rhIGF-I was infused into rats on the high-protein diet, significantly elevated levels of IGF-I in muscle tissues could be observed. This was associated with a significantly (P < 0.05) increased N balance, whereas rhGH significantly (P < 0.05) enhanced the N balance in rats on the low-protein diet. Thus, it can be concluded that the level of dietary protein ingested regulates not only the effect of IGF-I on whole-body N economy but also the regulation of IGF-I gene expression in muscles. The exact mechanism by which GH exerts its protein anabolic effect, however, remains to be elucidated.
Asunto(s)
Proteínas en la Dieta/administración & dosificación , Hormona del Crecimiento/sangre , Factor I del Crecimiento Similar a la Insulina/metabolismo , Nitrógeno/metabolismo , Animales , Metabolismo Energético , Femenino , Hormona del Crecimiento/administración & dosificación , Humanos , Factor I del Crecimiento Similar a la Insulina/administración & dosificación , Factor I del Crecimiento Similar a la Insulina/genética , Músculos/efectos de los fármacos , Músculos/metabolismo , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/metabolismoRESUMEN
To investigate the role of glutamate transport in non-synaptic glia, we characterized the expression of three major glutamate transporters (EAAC1, GLAST and GLT-1) in rat optic nerve in situ using reverse transcription-polymerase chain reaction in combination with Western blot and immunochemistry with specific antibodies. GLAST was localized to interfascicular oligodendrocytes, whereas a subpopulation of cells, probably immature oligodendrocyte cells, expressed EAAC1. In contrast, astrocytes, expressed only GLT-1, consistent with the idea that this is the major glutamate transporter in this cell type. In addition, we observed that glutamine synthetase, a key enzyme in glutamate metabolism, was localized in oligodendrocytes in situ. To examine the properties of these glutamate transporters, we conducted uptake experiments in glial cultures. The kinetics of sodium-dependent glutamate uptake in cultured oligodendrocytes from the perinatal rat optic nerve were markedly different from those observed in type-1 astrocytes from the newborn rat cerebral cortex, with higher affinity and lower Vmax. In both cell types, glutamate transport was inhibited by L-trans-pyrrolidine-2,4-dicarboxylate (t-PDC). In contrast, dihydrokainate exhibited significantly more uptake inhibition in oligodendrocytes than in type-1 astrocytes. These results provide evidence for the expression of functional sodium-dependent glutamate transporters in optic nerve oligodendrocytes, and suggest that this cell type may play a role in the glutamate-glutamine cycle.
Asunto(s)
Transportadoras de Casetes de Unión a ATP/metabolismo , Oligodendroglía/metabolismo , Nervio Óptico/metabolismo , Sistema de Transporte de Aminoácidos X-AG , Animales , Transporte Biológico/fisiología , Células Cultivadas , Glutamato-Amoníaco Ligasa/metabolismo , Ácido Glutámico/metabolismo , Neuroglía/metabolismo , Nervio Óptico/citología , Nervio Óptico/enzimología , Isoformas de Proteínas/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
Glial cells communicate reciprocally with neurons in multiple ways, both in synaptic and non-synaptic regions of the central nervous system. In the latter, neuron to glial and glial to glial signals can be mediated by neurotransmitters. Here, we review the presence and some of the functional properties of glutamate transporters and receptors in oligodendrocytes. In addition, we present data illustrating that alterations in glutamate homeostasis can be excitotoxic to oligodendroglia and that the tissue lesions caused by overactivation of glutamate receptors resemble those observed in demyelinating diseases such as multiple sclerosis. Overall, this information indicates that aberrant glutamate signaling may contribute to the development of some white matter pathologies.
Asunto(s)
Enfermedades del Sistema Nervioso Central/fisiopatología , Sistema Nervioso Central/fisiopatología , Enfermedades Desmielinizantes/fisiopatología , Ácido Glutámico/metabolismo , Animales , Comunicación Celular , Sistema Nervioso Central/fisiología , Homeostasis , Humanos , Sinapsis/fisiologíaRESUMEN
A working model for haematopoietic cytokine signal transduction has been hypothesised as follows. Binding of cytokines to specific receptor molecules leads to phosphorylation and activation of receptor associated members of the Janus kinase family. This is followed by tyrosine phosphorylation of the associated receptor and members of the STAT (signal transducer and activator of transcription) family of DNA-binding transcription factors. Phosphorylation is accompanied by STAT dimerisation, nuclear transport and activation of gene transcription. Activation of gene transcription is mediated by the binding of STAT dimers to palindromic STAT response elements. A number of areas of confusion remain; not least the mechanism by which multiple cytokines signal via a limited number of STATs. A role has been suggested for phosphorylated receptor tyrosine residues as STAT docking sites on activated receptor-JAK complexes. According to this model the amino acid sequence context of key tyrosine residues confers receptor specificity upon STAT activation. There is some controversy as to whether this model applies to STAT 5. The heterologous expression of STAT 5 in Sf 9 insect cells using the baculovirus expression system is described here. Protein of the correct molecular weight was expressed and found to be phosphorylated on tyrosine residues and to bind to a STAT response DNA element. This binding was dependent upon the phosphorylation status of the STAT protein. DNA binding could be abolished in vitro by treatment with a phosphotyrosine phosphatase and restored in vitro by treatment with activated recombinant JAK 2. The protein was purified to near homogeneity using a simple ion exchange/gel filtration chromatography procedure. The interaction between purified recombinant STAT 5 and JAK 2, either expressed by baculovirus or endogenously expressed in Buffalo rat liver cells, was studied. In both cases STAT 5 in its non-phosphorylated form was found to form a stable complex with activated JAK 2. Non-activated JAK 2 and phosphorylated STAT 5 were unable to participate in complex formation. The results presented provide a mechanistic basis for the activation of STAT 5 by a wide range of cytokines capable of activating JAK 2.