RESUMEN
Approved drug treatments for Alzheimer´s disease (AD) are symptomatic and don´t modify the disease course. These include acetylcholinesterase inhibitors (AchI) and N-methyl-D-aspartate receptor antagonist, memantine. Around 20 years ago, these drugs were approved for Alzheimer type Dementia. This wasbased on clinical trials which inclusion criteria were focused on a clinical amnestic AD presentation. At that time, subjects with an atypical AD clinical presentation or biomarkers were not included in the pharmacological trials. New biomarkers that detect amyloid and neurodegeneration have allowed us to evaluate pathological changes compatible with AD. These new advances from aclinical and biomarkers perspective allowed a diagnostic criteria update; going from an exclusively clinical criteria to one that is hybrid: clinical presentation and biomarkers based criteria.New biomarkers facilitate the early diagnosis of AD and other dementias.However, they also generate new challenges and questions regarding the adequate pharmacological treatment.There is a need for clinical trials that evaluate anti-dementia drug's efficacy based on current diagnostic criteria (clinical profile and biomarkers) and new practice guidelines. In addition, regulatory authorities should update ACHI and memantine indications.This will help doctors to prescribe the best possible treatment for this specific population without increasing risks.
Los tratamientos farmacológicos aprobados para la enfermedad de Alzheimer (EA) son sintomáticos y no modifican el curso de la enfermedad. Estos incluyen inhibidores de la acetilcolinesterasa (IACE) y el antagonista del receptor de N-metil-D-aspartato, memantina. Estos medicamentos fueron aprobados para la demencia de tipo Alzheimer (DTA) hace unos 20 años, basándose en ensayos clínicos centrados en la presentación clínica amnésica de la EA sin considerar biomarcadores o presentaciones clínicas atípicas de EA. Los nuevos biomarcadores que detectan amiloide y neurodegeneración nos han permitido evaluar cambios patológicos compatibles con la EA. Estos nuevos avances desde la perspectiva de los biomarcadores y clínicos han llevado a una actualización de los criterios diagnósticos, pasando de criterios exclusivamente clínicos a criterios híbridos: clínicos y basados en marcadores. Estos biomarcadores facilitan el diagnóstico precoz de la EA y otras demencias; sin embargo, a veces generan desafíos y replanteos en relación al tratamiento farmacológico adecuado. Sería útil implementar ensayos clínicos que evalúen la eficacia de los fármacos aprobados para la enfermedad de Alzheimer, en su momento con criterios de demencia tipo Alzheimer en función de los criterios diagnósticos actuales (perfil clínico y biomarcadores). Además, la actualización de la indicación de prescripción de IACE y memantina por parte de las autoridades regulatorias especificando con más detalle la población objetivo ayudaría a prescribir el mejor tratamiento posible a los pacientes sin aumentar los riesgos.
Asunto(s)
Enfermedad de Alzheimer , Biomarcadores , Humanos , Estudios RetrospectivosRESUMEN
Transcription activator-like effectors (TALEs) are important effectors of Xanthomonas spp. that manipulate the transcriptome of the host plant, conferring susceptibility or resistance to bacterial infection. Xanthomonas citri ssp. citri variant AT (X. citri AT ) triggers a host-specific hypersensitive response (HR) that suppresses citrus canker development. However, the bacterial effector that elicits this process is unknown. In this study, we show that a 7.5-repeat TALE is responsible for triggering the HR. PthA4AT was identified within the pthA repertoire of X. citri AT followed by assay of the effects on different hosts. The mode of action of PthA4AT was characterized using protein-binding microarrays and testing the effects of deletion of the nuclear localization signals and activation domain on plant responses. PthA4AT is able to bind DNA and activate transcription in an effector binding element-dependent manner. Moreover, HR requires PthA4AT nuclear localization, suggesting the activation of executor resistance (R) genes in host and non-host plants. This is the first case where a TALE of unusually short length performs a biological function by means of its repeat domain, indicating that the action of these effectors to reprogramme the host transcriptome following nuclear localization is not limited to 'classical' TALEs.
Asunto(s)
Proteínas Bacterianas/metabolismo , Enfermedades de las Plantas/microbiología , Xanthomonas/metabolismo , Xanthomonas/patogenicidad , Proteínas Bacterianas/genética , Citrus/microbiología , Nicotiana/microbiologíaRESUMEN
Charcoal rot, caused by the fungus Macrophomina phaseolina, is an economically important disease of soybean (Glycine max) worldwide. Objectives of the present research were to (i) study the genetic and pathogenic diversity in a collection of M. phaseolina isolates from Argentina and Paraguay and (ii) develop an improved in vitro phenotyping method to evaluate disease response of soybean genotypes to M. phaseolina isolates. Cluster analysis showed no clear association among simple sequence repeat profiles, year of collection, pathogenicity, and geographical origin of the isolates from Argentina and Paraguay. Subsequently, the response of four soybean genotypes against seven M. phaseolina isolates was evaluated in the field and the results were confirmed using the in vitro assay developed. This assay, which is based on root disease development on soybean seedlings, allowed the detection of a differential level of aggressiveness among the isolates on four soybean genotypes. The results suggest the existence of specific interactions among soybean genotypes and M. phaseolina isolates. In addition, cultivar Munasqa RR showed a superior response against M. phaseolina compared with DT 97-4290 (moderately resistant), thus becoming a novel source of resistance to charcoal rot.
Asunto(s)
Ascomicetos/patogenicidad , Resistencia a la Enfermedad/genética , Glycine max/genética , Enfermedades de las Plantas/genética , Argentina , Genotipo , Paraguay , Fenotipo , Enfermedades de las Plantas/microbiología , Glycine max/microbiologíaRESUMEN
Citrus is an economically important fruit crop that is severely afflicted by citrus canker, a disease caused by Xanthomonas citri ssp. citri (X. citri); thus, new sustainable strategies to manage this disease are needed. Although all Citrus spp. are susceptible to this pathogen, they are resistant to other Xanthomonas species, exhibiting non-host resistance (NHR), for example, to the brassica pathogen X. campestris pv. campestris (Xcc) and a gene-for-gene host defence response (HDR) to the canker-causing X. fuscans ssp. aurantifolii (Xfa) strain C. Here, we examine the plant factors associated with the NHR of C. limon to Xcc. We show that Xcc induced asymptomatic type I NHR, allowing the bacterium to survive in a stationary phase in the non-host tissue. In C. limon, this NHR shared some similarities with HDR; both defence responses interfered with biofilm formation, and were associated with callose deposition, induction of the salicylic acid (SA) signalling pathway and the repression of abscisic acid (ABA) signalling. However, greater stomatal closure was seen during NHR than during HDR, together with different patterns of accumulation of reactive oxygen species and phenolic compounds and the expression of secondary metabolites. Overall, these differences, independent of Xcc type III effector proteins, could contribute to the higher protection elicited against canker development. We propose that Xcc may have the potential to steadily activate inducible defence responses. An understanding of these plant responses (and their triggers) may allow the development of a sustained and sustainable resistance to citrus canker.
Asunto(s)
Citrus/microbiología , Enfermedades de las Plantas/genética , Enfermedades de las Plantas/microbiología , Xanthomonas campestris/patogenicidad , Ácido Abscísico/metabolismo , Citrus/metabolismo , Regulación de la Expresión Génica de las Plantas , Especies Reactivas de Oxígeno/metabolismo , Ácido Salicílico/metabolismoRESUMEN
Abstract: Introduction: Sleep quality is commonly impaired in medical disorders, and the HIV-positive population is particularly vulnerable to complaint from sleep disturbances. Objective: To determine the prevalence of poor sleep quality and the factors associated with it, in a population of HIV positive Mexican out patients. Method: A cross sectional study was done. A sample of 367 HIV-positive subjects over 18 years completed a set of self-administered questionnaires: the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale, the Athens Insomnia Scale, and the Beck Depression Inventory. Sociodemographic and clinical data were recorded. Results: Of the respondents, 82.8% (n = 304) were male. The mean age of the patients was 36.6 (SD = 9.4) years, and the mean educational level was 12.2 (SD = 3.8) years. According to the PSQI, 58.6% (n = 215) had poor sleep quality. Poor sleep quality was more common in those who had lived longer with HIV, had started their antiretroviral treatment later, had suboptimal antiretroviral adherence, had a CD4 cell count <200 cells/µL, reported illicit drug use, had concomitant medications, or had insomnia, sleepiness, or depressive symptoms. In multivariate analyses, poor sleep quality was associated with depressive symptoms, illicit drug use, a CD4 count <200 cells/µL, and time elapsed since HIV diagnosis. Discussion and conclusion: Poor sleep quality is common in HIV patients. Early identification of patients with poor sleep quality through vigilance for factors associated with it might facilitate prompt treatment.
Resumen: Introducción: La población seropositiva es particularmente vulnerable a presentar alteraciones del sueño. Objetivo: Determinar la prevalencia y los factores asociados a la mala calidad del sueño en un grupo de pacientes con VIH en la Ciudad de México. Método: Estudio transversal. Se incluyó una muestra de 367 personas con VIH mayores de 18 años. Todos los pacientes contestaron el Índice de Calidad del Sueño de Pittsburgh (PSQI), la Escala de Somnolencia de Epworth, la Escala de Atenas de Iinsomnio y el Inventario de Depresión de Beck. Se recabaron datos sociodemográficos y clínicos. Resultados: El 82.8% (n = 304) de los encuestados eran varones. La edad media fue de 36.6 (DE = 9.4), con escolaridad promedio de 12.2 (DE = 3.8) años. El 58.6% (n = 215) tuvieron una mala calidad del sueño. La mala calidad del sueño fue más común en aquellos con mayor tiempo de haber sido diagnosticados, con mayor retardo en el inicio y adherencia subóptima al tratamiento antirretroviral, con recuento de linfocitos T-CD4+ <200 células/µL, con uso ilícito de drogas y uso de medicamentos concomitantes, o con presencia de insomnio, somnolencia y síntomas depresivos. En el análisis multivariado, la mala calidad del sueño se asoció con síntomas depresivos, uso de drogas ilícitas, un recuento de linfocitos T-CD4+ <200 células/µL y el tiempo desde el diagnóstico de VIH. Discusión y conclusión: La mala calidad del sueño es común en pacientes con VIH. Su identificación temprana a través de la vigilancia de los factores asociados con ella puede facilitar el tratamiento oportuno.
RESUMEN
Xanthomonas citri ssp. citri (X. citri) is the causal agent of Asiatic citrus canker, a disease that seriously affects most commercially important Citrus species worldwide. We have identified previously a natural variant, X. citri AT , that triggers a host-specific defence response in Citrus limon. However, the mechanisms involved in this canker disease resistance are unknown. In this work, the defence response induced by X. citri AT was assessed by transcriptomic, physiological and ultrastructural analyses, and the effects on bacterial biofilm formation were monitored in parallel. We show that X. citri AT triggers a hypersensitive response associated with the interference of biofilm development and arrest of bacterial growth in C. limon. This plant response involves an extensive transcriptional reprogramming, setting in motion cell wall reinforcement, the oxidative burst and the accumulation of salicylic acid (SA) and phenolic compounds. Ultrastructural analyses revealed subcellular changes involving the activation of autophagy-associated vacuolar processes. Our findings show the activation of SA-dependent defence in response to X. citri AT and suggest a coordinated regulation between the SA and flavonoid pathways, which is associated with autophagy mechanisms that control pathogen invasion in C. limon. Furthermore, this defence response protects C. limon plants from disease on subsequent challenges by pathogenic X. citri. This knowledge will allow the rational exploitation of the plant immune system as a biotechnological approach for the management of the disease.
Asunto(s)
Citrus/microbiología , Enfermedades de las Plantas/microbiología , Xanthomonas/patogenicidad , Autofagia/fisiología , Biopelículas , Regulación de la Expresión Génica de las Plantas , Inmunidad de la Planta/fisiología , Ácido Salicílico/metabolismoRESUMEN
Citrus is an economically important fruit crop that is severely afflicted by Asiatic citrus bacterial canker (CBC), a disease caused by the phytopathogen Xanthomonas citri subsp. citri (X. citri). To gain insight into the molecular epidemiology of CBC, 42 Xanthomonas isolates were collected from a range of Citrus spp. across 17 different orchards in Tucumán, Argentina and subjected to molecular, biochemical, and pathogenicity tests. Analysis of genome-specific X. citri markers and DNA polymorphisms based on repetitive elements-based polymerase chain reaction showed that all 42 isolates belonged to X. citri. Interestingly, pathogenicity tests showed that one isolate, which shares >90% genetic similarity to the reference strain X. citri T, has host range specificity. This new variant of X. citri subsp. citri, named X. citri A(T), which is deficient in xanthan production, induces an atypical, noncankerous chlorotic phenotype in Citrus limon and C. paradisi and weak cankerous lesions in C. aurantifolia and C. clementina leaves. In C. limon, suppression of canker development is concomitant with an oxidative burst; xanthan is not implicated in the phenotype induced by this interaction, suggesting that other bacterial factors would be involved in triggering the defense response.
Asunto(s)
Citrus/inmunología , Citrus/microbiología , Enfermedades de las Plantas/inmunología , Enfermedades de las Plantas/microbiología , Xanthomonas/fisiología , Interacciones Huésped-Patógeno , Cloruro de Magnesio , Hojas de la Planta , Polisacáridos BacterianosRESUMEN
CD8+ T cells are crucial in protecting against viral infections by secreting antiviral factors and lysing infected cells. The loss of these functions is a hallmark of various chronic viral infections. In HIV chronic infection, CD8+ T cells develop this exhausted phenotype and their protection capacities diminish. Recently, it has been shown that a co-inhibitory molecule called PD-1 plays an important role on this exhausted phenotype. These findings open up the possibility of research targeted to develop therapeutic interventions that may restore CD8+ T cell function in chronic HIV infection.
Asunto(s)
Antígenos CD/fisiología , Proteínas Reguladoras de la Apoptosis/antagonistas & inhibidores , Proteínas Reguladoras de la Apoptosis/fisiología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Humanos , Inmunidad Celular , Receptor de Muerte Celular Programada 1RESUMEN
Lead is a multiple-source pollutant, well known for its toxicity, of great risk both for the environment and human health. The main target organs of lead are the hematopoietic, nervous, and renal systems; there are also reports in support of its impairment effects on the reproductive and immune systems. It is well known that most of the metal is accumulated in the blood cells and that many of the deleterious effects are related to its circulating concentrations. These adverse effects have been described not only in humans but also in a number of other vertebrates such as fish and birds. The purpose of the present work was to evaluate the effects of weekly administration of sublethal Pb (as acetate, 50 mg x kg(-1)) during 6 weeks on the profile of the serum proteins and blood cell counts of the adult South American toad, Bufo arenarum (Anura: Bufonidae). The electrophoretic patterns of serum proteins pointed out the presence of four fractions; the metal provoked a significant decrease in both total proteins and albumin fraction; among the globulin fractions, the G3 resulted augmented. These findings may be related to the impact of lead on the toads' hepatic cells and immune system. The number of total red blood cells (RBC) showed a tendency to decrease after the injections of the metal, whereas the number of white blood cells (WBC) increased significantly; the differential leukocyte counts showed a statistically significant increase in the absolute number and in the relative percentage of blast-like cells. The decrease in RBC was attributed to the negative impact of the metals on the hemoglobin synthesis. The increasing of the WBC counts may be interpreted as a consequence of the induction of proliferation of pluripotential hematopoietic cells.
Asunto(s)
Bufo arenarum , Compuestos Organometálicos/toxicidad , Animales , Bufo arenarum/sangre , Bufo arenarum/metabolismo , Contaminantes Ambientales/sangre , Contaminantes Ambientales/toxicidad , Recuento de Eritrocitos , Plomo/sangre , Recuento de Leucocitos , Masculino , Albúmina Sérica/metabolismo , Seroglobulinas/metabolismoRESUMEN
Galectins are a family of animal lectins defined by two properties: shared amino acid sequences in their carbohydrate-recognizing domain, and beta-galactoside affinity. A wide variety of biological phenomena are related to galectins, i.e., development, differentiation, morphogenesis, tumor metastasis, apoptosis, RNA splicing, and immunoregulatory function. In this review, we will focus on galectin-1 receptors, and some of the mechanisms by which this lectin affects different cell types. Several galectin-1 receptors are discussed such as CD45, CD7, CD43, CD2, CD3, CD4, CD107, CEA, actin, extracellular matrix proteins such as laminin and fibronectin, glycosaminoglycans, integrins, a beta-lactosamine glycolipid, GM1 ganglioside, polypeptide HBGp82, glycoprotein 90 K/MAC-2BP, CA125 cancer antigen, and pre-B cell receptor.
Asunto(s)
Galectina 1/metabolismo , Receptores de Superficie Celular/metabolismo , Animales , Antígenos CD/metabolismo , Matriz Extracelular/metabolismo , Gangliósido G(M1)/metabolismo , HumanosRESUMEN
Galectins are a family of animal lectins defined by their beta-galactoside-binding activities and a consensus sequence in their carbohydrate-recognizing domain (CRD). Relevant roles of galectins are described in adaptive immune response, innate immunity and modulation of the acute inflammatory response. We have extended our previous studies on a porcine spleen galectin-1 in relation to its functional roles such as polymorphonuclear neutrophils (PMNs) stimulation compared to well known PMN activators e.g. N-formyl-L-methionyl-L leucyl-L-phenylalanine (fMLP) and phorbol 12-myristate 13-acetate (PMA). Relative to activation of NADPH-oxidase fMLP and PMA are stronger than galectin-1 plus cytochalasin B (CB) when the lectin is employed at low concentrations (gal-1 1 microM, 3.6+0.8 nm O(2)(-)/min/10(7) PMN). Higher doses of galectin-1 (10 microM) plus CB produced a significant activation of NADPH-oxidase (27.9+14.8 nm O(2)(-)/min/10(7) PMN) and stimulated PMN degranulation up to 50%. We propose that local galectin-1 concentrations under physiological conditions might reach suitable levels for pig PMN stimulation, and might be a natural inducer of O(2)(-) formation or degranulation. Porcine galectins might produce enhanced responses in vivo when they stimulate neutrophils in combination with some other stimuli.
Asunto(s)
Galectina 1/farmacología , N-Formilmetionina Leucil-Fenilalanina/farmacología , Neutrófilos/fisiología , Estallido Respiratorio/efectos de los fármacos , Acetato de Tetradecanoilforbol/farmacología , Animales , Secuencia de Carbohidratos , Degranulación de la Célula/efectos de los fármacos , Galectina 1/aislamiento & purificación , Galectina 1/fisiología , Datos de Secuencia Molecular , Muramidasa/metabolismo , NADPH Oxidasas , Neutrófilos/efectos de los fármacos , Preparaciones de Plantas/farmacología , Proteínas de Plantas/farmacología , Proteínas Inactivadoras de Ribosomas , Proteínas Inactivadoras de Ribosomas Tipo 2 , Homología de Secuencia de Aminoácido , Bazo/química , Superóxidos/metabolismo , Porcinos , Toxinas Biológicas/farmacologíaRESUMEN
Biotechnological uses of plant cell-tissue culture usually rely on constitutive transgene expression. However, such expression of transgenes may not always be desirable. In those cases, the use of an inducible promoter could be an alternative approach. To test this hypothesis, we developed two binary vectors harboring a stress-inducible promoter from Arabidopsis thaliana, driving the beta-glucuronidase reporter gene and the oat arginine decarboxylase. Transgenic hairy roots of Lotus corniculatus were obtained with osmotic- and cold-inducible beta-glucuronidase and arginine decarboxylase activities. The increase in the activity of the latter was accompanied by a significant rise in total free polyamines level. Through an organogenesis process, we obtained L. corniculatus transgenic plants avoiding deleterious phenotypes frequently associated with the constitutive over-expression of arginine decarboxylation and putrescine accumulation.
Asunto(s)
Lotus/genética , Raíces de Plantas/metabolismo , Arabidopsis/genética , Avena/enzimología , Carboxiliasas/biosíntesis , Carboxiliasas/metabolismo , Técnicas de Cultivo , Vectores Genéticos , Glucuronidasa/genética , Glucuronidasa/metabolismo , Cinética , Ósmosis , Fenotipo , Plásmidos/metabolismo , Poliaminas/química , Poliaminas/metabolismo , Regiones Promotoras Genéticas , Putrescina/metabolismo , Factores de Tiempo , TransgenesRESUMEN
La medición de viscosidad plasmática y de sangre entera, determinadas en un viscosímetro rotacional, fue utilizada para verificar la existencia de anormalidaes hemorreológicas en pacientes diabéticos e hipertensos. Dichas mediciones se realizaron a distintas velocidades de corte, con lo cual se trazaron los correspondientes reogramas. Con esos datos se calcularon las correspondientes viscosidades relativas. Los resultados obtenidos, comparados con valores de los mismos parámetros obtenidos en individuos normales, permitiernon detectar comportamientos anormales, característicos de esas patologías circulatorias. Las diferencias más significativas se obtuvieron a una velocidad de corte de 5,76 seg. Se concluye que, en los pacientes diabéticos, los factores plasmáticos tienen mayor influencia en la aparición de hiperviscosidad, mientras que en los pacientes hipertensos son más influyentes los factores globulares (AU)
Asunto(s)
Humanos , Masculino , Femenino , Estudio Comparativo , Viscosidad Sanguínea , Hemorreología/estadística & datos numéricos , Hemorreología/métodos , Diabetes Mellitus/sangre , Hipertensión/sangreRESUMEN
La medición de viscosidad plasmática y de sangre entera, determinadas en un viscosímetro rotacional, fue utilizada para verificar la existencia de anormalidaes hemorreológicas en pacientes diabéticos e hipertensos. Dichas mediciones se realizaron a distintas velocidades de corte, con lo cual se trazaron los correspondientes reogramas. Con esos datos se calcularon las correspondientes viscosidades relativas. Los resultados obtenidos, comparados con valores de los mismos parámetros obtenidos en individuos normales, permitiernon detectar comportamientos anormales, característicos de esas patologías circulatorias. Las diferencias más significativas se obtuvieron a una velocidad de corte de 5,76 seg. Se concluye que, en los pacientes diabéticos, los factores plasmáticos tienen mayor influencia en la aparición de hiperviscosidad, mientras que en los pacientes hipertensos son más influyentes los factores globulares