ABSTRACT
Neuronal aging may be, in part, related to a change in DNA methylation. Thus, methyl donors, like folate and methionine, may play a role in cognitive changes associated to neuronal aging. To test the role of these metabolites, we performed stereotaxic microinjection of these molecules into the dentate gyrus (DG) of aged mice (an average age of 21 month). Folate, but not S-Adenosyl-Methionine (SAM), enhances cognition in aged mice. In the presence of folate, we observed partial rejuvenation of DG cells, characterized by the expression of juvenile genes or reorganization of extracellular matrix. Here, we have also tried to identify the mechanism independent of DNA methylation, that involve folate effects on cognition. Our analyses indicated that folate binds to folate receptor α (FRα) and, upon folate binding, FRα is transported to cell nucleus, where it is acting as transcription factor for expressing genes like SOX2 or GluN2B. In this work, we report that a FRα binding peptide also replicates the folate effect on cognition, in aged mice. Our data suggest that such effect is not sex-dependent. Thus, we propose the use of this peptide to improve cognition since it lacks of folate-mediated side effects. The use of synthetic FRα binding peptides emerge as a future strategy for the study of brain rejuvenation.
Subject(s)
Folate Receptor 1 , Rejuvenation , Animals , Mice , Cognition , Dentate Gyrus/metabolism , Folate Receptor 1/metabolism , Folic Acid/metabolism , Methionine , Peptides/metabolism , S-AdenosylmethionineABSTRACT
Introducción y objetivo: muchos pacientes en situación terminal son atendidos en las últimas etapas de su vida en servicios médicos y fuera de unidades de cuidados paliativos. Por ello nos propusimos estudiar y describirlas historias clínicas de los pacientes fallecidos en nuestro servicio durante el año 2006. Pacientes y métodos: estudio retrospectivo descriptivo de las historias clínicas de los pacientes fallecidos durante el año 2006 en el Servicio de Medicina Interna del Hospital Virgen de la Torre (HVTR) -Madrid-. Se analizaron datos sociodemográficos, clínicos, criterios de terminalidad, causas de muerte y tipo de cuidados recibidos, instrumentalización, existencia de Voluntades Anticipadas e inclusión en protocolo de paliativos. Se analizaron los resultados con el programa estadístico SPSS 14.0. Resultados: se obtuvieron 172 historias clínicas (64,5% mujeres,35,5% varones, edad media 85,76 ± 7,0) de los 188 pacientes fallecidos en dicho periodo. El 69% de los pacientes tenía criterios de terminalidad, siendo la enfermedad de base: demencias 52%, oncológicas 14%, obstrucción crónica del flujo aéreo (OCFA) 10%, e insuficiencia cardiaca (IC) 9%. Las causas del éxitus fueron respiratorias (70%), neurológicas (52%), cardiovasculares(35%) y sepsis (31%). Ningún paciente tenía voluntades anticipadas. Se incluyeron en protocolo de paliativos el 81% de los pacientes terminales. Conclusiones: un alto porcentaje de los pacientes que fallecieron en nuestro servicio cumplían criterios de terminalidad. El perfil del paciente más común fue el de una anciana de edad avanzada, pluripatológica, con alto nivel de dependencia, cuidada por su familia y con demencia en fase terminal. Ningún paciente tenía voluntades anticipadas (AU)
Background and objectives: many patients with end-stage chronic illnesses are cared for in medical services, outside specific palliative care resources. This encouraged us to review the patients that had died in our department during 2006, describing their characteristics and the care they were given. Patients and methods: a retrospective descriptive study of the clinical records of patients who died during 2006 at Internal Medicine Service, Virgen de la Torre Hospital, Madrid, Spain. We analyzed their sociodemographic and clinical information, end-stage disease criteria, causes of death, type of care and treatments, degree of instrumentalization, and presence of a living will. The results were analyzed with the statistical programSPSS 14.0. Results: we obtained 172 clinical records of 188 deceased patients during this period (64.5% women, 35.5% males, mean age 85.76 ± 7.0);69% of patients had end-stage disease, and diseases included dementia in 52%, cancer in 14%, COPD in 10%, and heart failure in 9%. Death was most commonly of respiratory (70%), neurological (52%), cardiovascular(35%), or septic (31%) cause. No patient had a living will; 81% of terminal patients were included in a palliative protocol. Conclusions: a high percentage of the patients that had died in our service had a terminal chronic disease. Patient type was a woman of advanced age, with multiple chronic diseases, with a high level of dependency, cared after by her family, and with end-stage dementia. No patient had a living will (AU)
Subject(s)
Humans , Male , Female , Aged , Aged, 80 and over , Internal Medicine/statistics & numerical data , Mortality/statistics & numerical data , Cause of Death , Retrospective Studies , Spain/epidemiologyABSTRACT
The aim of this paper is to determine the concentration of three dyes throughout the tanning process of leather using vegetable tanning agents with a sequential injection analyser with second-order data treatment. As the vegetable tanning agents used are highly absorbent species, we focus on three aspects: (i) difficulties with the resolution (ii) the reduction in the working concentration range; and (iii) matrix effects. Ideally, second-order instruments provide "second-order advantage"; i.e. calibration is possible in the presence of uncalibrated interfering species. However, if the interfering species change the instrumental response of the analyte (in scale or shape), standard additions must be used to ensure the accuracy of the estimated analyte concentration. Here we study the presence of matrix effects for three dyes in several samples in order to significantly improve the accuracy of predictions in the presence of such effects. We found that there were matrix effects in at least 80% of the samples with an alpha risk of 5%. We used this method to study the exhaustion of dyes in the dyeing process.
ABSTRACT
No disponible
Subject(s)
Middle Aged , Female , Humans , Klebsiella pneumoniae , Splenomegaly , Thromboembolism , Sepsis , Klebsiella Infections , FeverSubject(s)
Klebsiella Infections/diagnosis , Klebsiella pneumoniae , Sepsis/diagnosis , Thromboembolism/diagnostic imaging , Female , Fever/etiology , Humans , Klebsiella Infections/complications , Middle Aged , Radiography , Sepsis/complications , Splenomegaly/etiology , Thromboembolism/complications , Thromboembolism/microbiologyABSTRACT
OBJECTIVE: To analyze the characteristics of systemic necrotizing vasculitis observed in necropsy emphasizing the non-diagnosed cases until necropsy and to identify the reasons of clinical confusion. MATERIALS AND METHODS: Necropsies of adult patients performed in Hospital General La Paz, Madrid, from 1966 to 1977 were reviewed. Clinical manifestations, analytical changes and involvement of different organs were analyzed. The correspondence degree between clinical and necropsic diagnoses was studied. RESULTS: A total of 18 cases of necrotizing vasculitis were observed out of 3,980 necropsies. The most common clinical manifestations were fever and general syndrome (60%). The organs most commonly involved were kidney (94%) and gastrointestinal tract (56%). Diagnosis was revealed by necropsy in 39% of cases; in these cases, the incidence of heart failure and peripheral neuropathy was significantly lower, whereas digestive hemorrhage and liver, pancreas, adrenal gland, and bladder involvement was significantly higher. CONCLUSIONS: Systemic necrotizing vasculitis in underdiagnosed, which can be partly explained by the lack of specificity of the most common symptoms and the paucity of characteristic clinical and organ-specific manifestations which leads to confusion with more prevalent conditions.
Subject(s)
Vasculitis/pathology , Adult , Aged , Aged, 80 and over , Autopsy , Female , Humans , Male , Middle Aged , NecrosisABSTRACT
Objetivo. Análisis de las características de las vasculitis necrosantes sistémicas observadas en la autopsia con énfasis en los casos no diagnosticados hasta la misma e identificar los motivos de confusión clínica. Material y métodos. Se revisaron las autopsias de adultos realizadas en el Hospital General La Paz de Madrid entre 1966-1997; se analizaron las manifestaciones clínicas, alteraciones analíticas y afectación de los diferentes órganos y se estudió el grado de correspondencia entre cada diagnóstico clínico y necrópsico. Resultados. En 3.980 autopsias se encontraron 18 casos de vasculitis necrosante sistémica. Las manifestaciones clínicas más frecuentes fueron fiebre y síndrome general (60 por ciento). Los órganos más frecuentemente afectados fueron riñón (94 por ciento) y tracto gastrointestinal (56 por ciento). En el 39 por ciento de los casos fue la autopsia la que reveló el diagnóstico; en estos casos la incidencia de insuficiencia cardíaca y neuropatía periférica fue significativamente más baja, mientras que la hemorragia digestiva y la afectación de hígado, páncreas, suprarrenales y vejiga fue significativamente mayor. Conclusiones. Las vasculitis necrosantes sistémicas se infradiagnostican; contribuyen a ello la inespecificidad de los síntomas más frecuentes, induciendo confusión con entidades más prevalentes y la escasez de manifestaciones clínicas características y órgano específicas (AU)
Subject(s)
Middle Aged , Adult , Aged, 80 and over , Aged , Male , Female , Humans , Vasculitis , Necrosis , AutopsyABSTRACT
A case of Hashimoto's thyroiditis associated with incomplete Sjögren's syndrome is revised. Both immune disorders are together not just as a casual event, but literature says that common mechanisms could have something to be. Previous publications express that autoimmune thyroid dysfunction is frequently associated with primary Sjögren's syndrome and should be sought clinically and by laboratory test in all these patients.
Subject(s)
Autoimmune Diseases/diagnosis , Sjogren's Syndrome/immunology , Thyroiditis, Autoimmune/immunology , Adult , Humans , Male , Sjogren's Syndrome/diagnosis , Syndrome , Thyroiditis, Autoimmune/diagnosisABSTRACT
Se describe un caso de tiroiditis de Hashimoto (TH) asociado a síndrome de Sjögren (SS) incompleto. Ambas enfermedades inmunológicas no sólo se encuentran asociadas como un hallazgo casual, sino que existen datos en la literatura que implican a mecanismos etiopatogénicos comunes. Publicaciones previas manifiestan que la disfunción tiroidea autoinmune está frecuentemente asociada al SS primario y debería ser investigada, clínica y analíticamente, en todos estos pacientes. (AU)
Subject(s)
Adult , Male , Humans , Thyroiditis, Autoimmune , Syndrome , Autoimmune Diseases , Sjogren's SyndromeABSTRACT
A correlation between hyperphosphorylation of tau protein and its aberrant assembly into paired helical filaments has lead to suggestions that phosphorylation controls assembly, but lacked a mechanistic basic. In this work, we have found that phosphorylated, but not native, tau protein is able to form polymers after the reaction with 4-hydroxy-2-nonenal, a highly toxic product of lipid peroxidation. Phosphorylation of tau by both proline or non-proline directed kinases, was able to assemble it into polymers.
Subject(s)
tau Proteins/metabolism , Aldehydes/pharmacology , Animals , COS Cells , Calcium-Calmodulin-Dependent Protein Kinases/antagonists & inhibitors , Calcium-Calmodulin-Dependent Protein Kinases/metabolism , Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors , Cyclic AMP-Dependent Protein Kinases/metabolism , Dose-Response Relationship, Drug , Enzyme Inhibitors/pharmacology , Glycogen Synthase Kinase 3 , Neurofibrillary Tangles/chemistry , Neurofibrillary Tangles/metabolism , Neurofibrillary Tangles/ultrastructure , Okadaic Acid/pharmacology , Peptides/chemistry , Peptides/metabolism , Phosphoric Monoester Hydrolases/antagonists & inhibitors , Phosphorylation/drug effects , Protein Conformation/drug effects , Protein Serine-Threonine Kinases/metabolism , Transfection , tau Proteins/genetics , tau Proteins/isolation & purificationABSTRACT
Spisulosine is a novel antiproliferative (antitumoral) compound of marine origin. In this work the molecular target for this toxic agent has been analyzed. In the presence of spisulosine, cultured cells change their morphology, first acquiring a fusiform morphology, and later becoming rounded without focal adhesions. Analysis of the cytoskeleton of treated cells indicate the absence of actin stress fibers.
Subject(s)
Actins/drug effects , Lipids/pharmacology , Animals , Bivalvia/chemistry , Cell Division/drug effects , Cell Line , Cell Size/drug effects , Chlorocebus aethiops , Dose-Response Relationship, Drug , Lysophospholipids/pharmacology , Tumor Cells, Cultured , Vero CellsABSTRACT
En este artículo se revisan el concepto y la terminología de los priones, su replicación y algunas hipótesis actuales de la naturaleza de estos agentes infecciosos que causan enfermedades neurodegenerativas. También se resumen los aspectos etiopatogénicos, epidemiológicos, clínicos y neuropatológicos de las enfermedades producidas por priones o encefalopatías espongiformes transmisibles humanas, y algunos métodos para su rápido diagnóstico. Finalmente, se comenta la posible relación entre la encefalopatía espongiforme bovina y los nuevos casos de enfermedad de Creutzfeldt-Jakob identificados en el Reino Unido (AU)
Subject(s)
Humans , Prion Diseases/diagnosis , Prion Diseases/epidemiology , Prion Diseases/etiology , Prion Diseases/physiopathology , PrionsABSTRACT
In this article we review the concept and terminology of prions, their replication and some current hypothesis on the nature of these infectious agents causing neurodegenerative diseases. This revision also summarizes the etiopathogenic, epidemiological, clinical and neuropathological features of the prion diseases or human transmissible spongiform encephalopathies, and some methods for their early diagnosis. Finally, we discuss the possible link between the bovine spongiform encephalopathy and the new cases of Creutzfeldt-Jakob disease identified in the United Kingdom.
Subject(s)
Prion Diseases , Prions , Humans , Prion Diseases/diagnosis , Prion Diseases/epidemiology , Prion Diseases/etiology , Prion Diseases/physiopathologyABSTRACT
Eight cases of sporotrichosis originating from the metropolitan area of Cusco, Peru, and its region are described, including the circumstances of infection and the isolation of Sporothrix schenckii from the lesions. This finding classifies this particular area with high altitude, low temperature and dry weather as an endemic zone of interest in the epidemiological and ecological study of Andean sporotrichosis. Among the eight cases observed, five were of the fixed cutaneous type and three were lymphocutaneous. Six patients were male and two female. Two paediatric cases were also observed. Therapy with potassium iodide was very satisfactory, whereas poor results were obtained with ketoconazole.
Subject(s)
Dermatomycoses/epidemiology , Ketoconazole/therapeutic use , Potassium Iodide/therapeutic use , Sporothrix/isolation & purification , Sporotrichosis/epidemiology , Adolescent , Adult , Aged , Child , Child, Preschool , Dermatomycoses/drug therapy , Female , Humans , Male , Peru/epidemiology , Sporotrichosis/drug therapyABSTRACT
Se presenta un caso de obstrucción intestinal por vólvulo asociado a gestación en el tercer trimestre, el cual fue sometido a laparatomía exploradora realizándose Cesárea-histerectomía más devolvulación, resección intestinal y colostomía tipo Hartman con evolución fetal favorable y morbilidad materna. Se revisa el caso y la literatura correspondiente en relación a vólvulo asociado a embarazo en cuanto a la evolución y manejo quirúrgico y se precisa la necesidad del diagnóstico y tratamiento oportuno para evitar la morbimortalidad materna y perinatal.
Subject(s)
Female , Adult , Humans , Pregnancy , Intestinal Obstruction , Pregnancy Trimester, ThirdABSTRACT
Siendo en la emergencia obstétrica, la Cesárea-Histerectomía una intervención necesaria para solucionar situaciones que ponga en riesgo la vida de las pacientes, presentamos, nuestra experiencia en este procedimiento en el Departamento de Ginecología-Obstétrica del H. M. I. San Bartolomé durante 25 años de funcionamiento 1962-1986; para lo cual se revisaron 74 historias clínicas. Esta presentación tiene por finalidad comparar nuestros resultados con los reportados en la literatura, acerca de un procedimiento que no deja se ser controversial.
