RESUMEN
Two unrelated boys, 12 and 9 years old, suffered from a diffuse cerebral disease that followed a parallel, subacute course. Mental regression, loss of hearing and vision, spastic-ataxic and pseudobulbar disturbances, and atrophy of the optic nerves occurred in both. Enzyme studies and the liver biopsy of one of the patients suggest a "lysosomal disease." The hallmark of both patients is the striking similarity of the cerebral scintigraphy and the computerized axial tomography (CT). Cerebral scintigraphy showed annular and crescent-shaped areas of increased radioactivity in the parietoccipital region. The CT indicated bilateral, symmetric bands of elevated density after contrast enhancement in the paraventricular white matter in the same region. These findings and the neurologic symptoms are compatible with leukodystrophy. Thus cerebral scintigraphy and CT appear to be useful aids in the diagnosis of metabolic brain disease. Computerized axial tomography is preferred for distinguishing whether lesions are in white or gray matter.
Asunto(s)
Encéfalo/diagnóstico por imagen , Esclerosis Cerebral Difusa de Schilder/diagnóstico , Tomografía Computarizada por Rayos X , Niño , Esclerosis Cerebral Difusa de Schilder/diagnóstico por imagen , Humanos , Leucocitos/enzimología , Hígado/ultraestructura , Lisosomas/enzimología , Masculino , Manosidasas/deficiencia , Cintigrafía , alfa-L-Fucosidasa/deficienciaAsunto(s)
Carboxipeptidasa B2/genética , Retroalimentación Fisiológica , Accidente Cerebrovascular , Terapia Trombolítica , Carboxipeptidasa B2/fisiología , Regulación de la Expresión Génica/efectos de los fármacos , Hemostasis/genética , Humanos , Activadores Plasminogénicos/administración & dosificación , Activadores Plasminogénicos/farmacología , Accidente Cerebrovascular/sangre , Accidente Cerebrovascular/terapiaAsunto(s)
Carboxipeptidasa B2/sangre , Carboxipeptidasa B2/genética , Pruebas Hematológicas/métodos , Isoleucina/genética , Polimorfismo Genético , Treonina/genética , Coagulación Sanguínea , Cromatografía Líquida de Alta Presión , Genotipo , Humanos , Cinética , Isoformas de Proteínas , Reproducibilidad de los Resultados , Factores de Riesgo , Temperatura , Factores de TiempoAsunto(s)
Carboxipeptidasa B2/sangre , Humanos , Indicadores y Reactivos , Cinética , Métodos , Análisis EspectralRESUMEN
BACKGROUND AND OBJECTIVES: Procarboxypeptidase U (proCPU, TAFI) concentration in plasma is potentially related to thrombotic tendency, and elevated proCPU levels have been reported in ischemic stroke patients. Improved insight into the role of proCPU in acute ischemic stroke is essential for the development of more adequate therapeutics that may include carboxypeptidase inhibitors. In this study we investigated whether the plasma concentration of proCPU and the proCPU kinetic profile in acute ischemic stroke are related to initial stroke severity, stroke evolution in the subacute phase and long-term stroke outcome. METHODS: Plasma concentration of proCPU was assessed in 136 stroke patients at admission (7.5 h after stroke onset), at 24 h, at 72 h and at day 7 after stroke onset. We evaluated the relation between change in proCPU concentrations and (a) stroke severity (patients with TIA vs. stroke patients, NIHSS score at admission), (b) stroke evolution (stroke progression, infarct volume at 72 h), and (c) stroke outcome (mRS score at month 3). RESULTS: ProCPU concentration decreased significantly in the first 72 h after stroke onset and thereafter returned to baseline. This biphasic time course, with its nadir at 72 h, was more pronounced in patients with severe stroke, unfavourable stroke evolution in the first 72 h and poor long-term outcome. CONCLUSIONS: The decrease in proCPU concentration in the first 72 h after stroke onset correlates with more severe stroke, unfavourable stroke evolution, and poor long-term stroke outcome.
Asunto(s)
Isquemia Encefálica/terapia , Carboxipeptidasa B2/sangre , Accidente Cerebrovascular/terapia , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Isquemia Encefálica/sangre , Isquemia Encefálica/complicaciones , Isquemia Encefálica/diagnóstico , Evaluación de la Discapacidad , Regulación hacia Abajo , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Medición de Riesgo , Factores de Riesgo , Índice de Severidad de la Enfermedad , Accidente Cerebrovascular/sangre , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/etiología , Factores de Tiempo , Resultado del TratamientoRESUMEN
Procarboxypeptidase U (TAFI) is a recently discovered plasma procarboxypeptidase that upon activation by thrombin or thrombin-thrombomodulin turns into a potent antifibrinolytic enzyme. Its prominent bridging function between coagulation and fibrinolysis raised the interest of many research groups and of the pharmaceutical industry. The development of carboxypeptidase U (CPU) inhibitors as profibrinolytic agents is an attractive concept and possibilities for rational drug design will become more readily available in the near future as a result of the recently published crystal structure. Numerous studies have been performed and many of them show beneficial effects of CPU inhibitors for the improvement of endogenous fibrinolysis in different animal sepsis and thrombosis models. CPU inhibitors combined with tissue-type plasminogen activator (t-PA) seem to increase the efficiency of pharmacological thrombolysis allowing lower dosing of t-PA and subsequently fewer bleeding complications. This review will focus on recently obtained in vivo data and the benefits/risks of targeting CPU for the treatment of thrombotic disorders.