RESUMEN
Multiple sclerosis (MS), especially in its progressive phase, involves early axonal and neuronal damage resulting from a combination of inflammatory mediators, demyelination, and loss of trophic support. During progressive disease stages, a microenvironment is created within the central nervous system (CNS) favoring the arrival and retention of inflammatory cells. Active demyelination and neurodegeneration have also been linked to microglia (MG) and astrocyte (AST)-activation in early lesions. While reactive MG can damage tissue, exacerbate deleterious effects, and contribute to neurodegeneration, it should be noted that activated MG possess neuroprotective functions as well, including debris phagocytosis and growth factor secretion. The progressive form of MS can be modeled by the prolonged administration to cuprizone (CPZ) in adult mice, as CPZ induces highly reproducible demyelination of different brain regions through oligodendrocyte (OLG) apoptosis, accompanied by MG and AST activation and axonal damage. Therefore, our goal was to evaluate the effects of a reduction in microglial activation through orally administered brain-penetrant colony-stimulating factor-1 receptor (CSF-1R) inhibitor BLZ945 (BLZ) on neurodegeneration and its correlation with demyelination, astroglial activation, and behavior in a chronic CPZ-induced demyelination model. Our results show that BLZ treatment successfully reduced the microglial population and myelin loss. However, no correlation was found between myelin preservation and neurodegeneration, as axonal degeneration was more prominent upon BLZ treatment. Concomitantly, BLZ failed to significantly offset CPZ-induced astroglial activation and behavioral alterations. These results should be taken into account when proposing the modulation of microglial activation in the design of therapies relevant for demyelinating diseases. Cover Image for this issue: https://doi.org/10.1111/jnc.15394.
Asunto(s)
Enfermedades Desmielinizantes , Esclerosis Múltiple , Animales , Factores Estimulantes de Colonias/efectos adversos , Factores Estimulantes de Colonias/metabolismo , Cuprizona/metabolismo , Cuprizona/toxicidad , Enfermedades Desmielinizantes/inducido químicamente , Enfermedades Desmielinizantes/tratamiento farmacológico , Enfermedades Desmielinizantes/metabolismo , Modelos Animales de Enfermedad , Ratones , Ratones Endogámicos C57BL , Microglía/metabolismo , Esclerosis Múltiple/metabolismo , Vaina de Mielina/metabolismoRESUMEN
Purpura fulminans (PF) is a rare syndrome of progressive haemorragic necrosis due to disseminated intravascular coagulation (DIC) and dermal vascular thrombosis leading to purpura and tissue necrosis. PF is more often associated with either a benign infection or a severe sepsis. Rarely, it has been related to drug intake. We report the case of a 24-year-old female patient who suffered from staphylococcal sepsis and pancytopenia, for which she was treated with antibiotics, granulocyte-colony stimulating factor (G-CSF) and granulocyte/macrophage CSF (GM-CSF). Two days after the last GM-CSF dose, she developed widespread necrotic plaques with erythematous borders and purpura in the breast, arms and legs. Coagulation tests indicated DIC and a skin biopsy showed fibrin thrombi in the superficial dermal vessels. The patient totally recovered after removal of the necrotic tissues and application of skin autografts. Although staphylococcal infection was most probably involved in the development of PF, a role of CSF cannot be excluded in this case.
Asunto(s)
Factores Estimulantes de Colonias/efectos adversos , Vasculitis por IgA/etiología , Sepsis/complicaciones , Infecciones Estafilocócicas/complicaciones , Adulto , Factores Estimulantes de Colonias/uso terapéutico , Coagulación Intravascular Diseminada/etiología , Femenino , Humanos , Vasculitis por IgA/inducido químicamente , Vasculitis por IgA/patología , Sepsis/tratamiento farmacológico , Piel/patología , Infecciones Estafilocócicas/tratamiento farmacológicoRESUMEN
El síndrome de Sweet es una entidad dermatológica poco frecuente, definida como una dermatosis neutrofílica febril aguda. Esta patología presenta características clínicas bien definidad, y en un porcentaje minoritario de pacientes está asociada a neoplasias sólidas. Presentamos el caso de una paciente de 71 años de edad que consulta debido a la aparición de placas eritemato-edematosas infiltradas y dolorosas en miembro superior y región mamaria derechas, extendiéndose a hemiabdomen homolateral y dorso, precedidas por fiebre y escalofríos. Como antecedentes personales de importancia destaca haber padecido cáncer de mama 4 años antes de la aparición de la dermatosis (AU)
Asunto(s)
Humanos , Femenino , Persona de Mediana Edad , Anciano , Síndrome de Sweet/diagnóstico , Neoplasias de la Mama/complicaciones , Neoplasias/complicaciones , Síndrome de Sweet/complicaciones , Síndrome de Sweet/etiología , Síndromes Paraneoplásicos , Iritis/etiología , Escleritis/etiología , Conjuntivitis/etiología , Proteinuria/etiología , Tretinoina/efectos adversos , Minociclina/efectos adversos , Litio/efectos adversos , Carbonato de Litio/efectos adversos , Factores Estimulantes de Colonias/efectos adversos , Embarazo , Colitis Ulcerosa/complicaciones , Enfermedad de Crohn/complicaciones , Artritis Reumatoide/complicacionesRESUMEN
El síndrome de Sweet es una entidad dermatológica poco frecuente, definida como una dermatosis neutrofílica febril aguda. Esta patología presenta características clínicas bien definidad, y en un porcentaje minoritario de pacientes está asociada a neoplasias sólidas. Presentamos el caso de una paciente de 71 años de edad que consulta debido a la aparición de placas eritemato-edematosas infiltradas y dolorosas en miembro superior y región mamaria derechas, extendiéndose a hemiabdomen homolateral y dorso, precedidas por fiebre y escalofríos. Como antecedentes personales de importancia destaca haber padecido cáncer de mama 4 años antes de la aparición de la dermatosis
Asunto(s)
Humanos , Femenino , Persona de Mediana Edad , Neoplasias de la Mama/complicaciones , Conjuntivitis/etiología , Iritis/etiología , Neoplasias/complicaciones , Síndromes Paraneoplásicos , Proteinuria/etiología , Escleritis/etiología , Síndrome de Sweet/complicaciones , Síndrome de Sweet/diagnóstico , Síndrome de Sweet/etiología , Artritis Reumatoide/complicaciones , Colitis Ulcerosa/complicaciones , Factores Estimulantes de Colonias/efectos adversos , Enfermedad de Crohn/complicaciones , Carbonato de Litio/efectos adversos , Litio/efectos adversos , Minociclina/efectos adversos , Embarazo , Tretinoina/efectos adversosAsunto(s)
Factores Estimulantes de Colonias/uso terapéutico , Leucopenia/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Anemia Aplásica/tratamiento farmacológico , Antineoplásicos/efectos adversos , Trasplante de Médula Ósea , Factores Estimulantes de Colonias/efectos adversos , Factores Estimulantes de Colonias/farmacología , Evaluación de Medicamentos , Hematopoyesis/efectos de los fármacos , Humanos , Leucopenia/etiología , Síndromes Mielodisplásicos/tratamiento farmacológico , Neoplasias/complicaciones , Proteínas Recombinantes/uso terapéuticoRESUMEN
8 patients with bone marrow failure after a caesium-137 radiation accident were treated with recombinant human granulocyte-macrophage colony stimulating factor (rHuGM-CSF). The 7 who were evaluable had prompt increases in granulocytes and bone marrow cellularity. 2 patients died of radiation toxicity and haemorrhage and 2 of bacterial sepsis acquired before the start of rHuGM-CSF treatment. 4 patients survive, including 2 who were treated early and never became infected. This therapeutic approach to radiation-induced granulocytopenia may therefore be useful after radiation and nuclear accidents.