RESUMEN
BACKGROUND: Pre-clinical assessment of bioartificial liver support systems requires a highly reproducible large animal model. The main objective of the present study was to develop a valid large animal model for assessing novel bioartificial liver support systems in fulminant hepatic failure. METHODS: A complete liver devascularization procedure was performed in 10 female pigs weighing 25-38 kg. Five matched pigs were sham-operated and served as controls. RESULTS: Pigs with fulminant hepatic failure developed a hyperdynamic circulation, with increased cardiac index (P(GT) < .0001), decreased systemic vascular resistance index (P(GT) < .0001) and mean arterial pressure (P(GT) = .001). Furthermore, intracranial hypertension developed (P(GT) < .0001). with increased common carotid artery flow (P(GT) < .0001) and decreased common carotid resistance (P(G) = .003). Femoral artery flow increased (P = .036). while hindleg resistance (P < .001) and renal artery resistance decreased (P = .019). Oxygen consumption (P(GT) = .050) and oxygen extraction ratio (P(GT) = .001) increased compared to controls. Arterial ammonia, venous aspartate aminotransferase and bilirubin levels increased (P(GT) < .0001, respectively). Abnormal haemostasis developed with significant loss of platelets (P(GT) = .010), decreasing fibrinogen levels (P(G) = .001) and increasing international normalized ratio (P(GT) = .012) and activated clotting time (PGT < .001). Urine became hypo-osmotic (P < .001. P(G) = .011), with decreased sodium levels (P = .08) and increased potassium levels (P(G) = .025). CONCLUSIONS: This study characterizes a reproducible large animal model for fulminant hepatic failure that seems suitable for the assessment of bioartificial liver support systems.
Asunto(s)
Fallo Hepático Agudo/terapia , Hígado Artificial , Modelos Animales , Animales , Análisis Químico de la Sangre , Pruebas de Coagulación Sanguínea , Femenino , Hemodinámica , Presión Intracraneal/fisiología , Circulación Hepática/fisiología , Fallo Hepático Agudo/sangre , Pruebas de Función Hepática , Consumo de Oxígeno/fisiología , Flujo Sanguíneo Regional , Porcinos , UrinálisisRESUMEN
OBJECTIVE: The present study was conducted to validate S-100 protein as a marker of brain damage after minor head injury. METHODS: We studied 50 patients with minor head injuries and Glasgow Coma Scale scores of 13 to 15 in whom computed tomographic scans of the brain revealed no abnormalities. Serum levels of S-100 protein were measured at admittance and hourly thereafter until 12 hours after injury. Magnetic resonance imaging and baseline neuropsychological examinations were performed within 48 hours, and neuropsychological follow-up was conducted at 3 months postinjury. RESULTS: Fourteen patients (28%) had detectable serum levels of S-100 protein (mean peak value, 0.4 microg/L [standard deviation, +/- 0.3]). The S-100 protein levels were highest immediately after the trauma, and they declined each hour thereafter. At 6 hours postinjury, the serum level was below the detection limit (0.2 microg/L) in five (36%) of the patients with initially detectable levels. Magnetic resonance imaging revealed brain contusions in five patients, four of whom demonstrated detectable levels of S-100 protein in serum. The proportion of patients with detectable serum levels was significantly higher when magnetic resonance imaging revealed a brain contusion. In patients with detectable serum levels, we observed a trend toward impaired neuropsychological functioning on measures of attention, memory, and information processing speed. CONCLUSION: Determination of S-100 protein levels in serum provides a valid measure of the presence and severity of traumatic brain damage if performed within the first hours after minor head injury.
Asunto(s)
Lesiones Encefálicas/diagnóstico , Lesiones Encefálicas/etiología , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Traumatismos Craneocerebrales/complicaciones , Traumatismos Craneocerebrales/fisiopatología , Pruebas Neuropsicológicas , Proteínas S100/sangre , Adolescente , Adulto , Anciano , Biomarcadores/sangre , Lesiones Encefálicas/sangre , Lesiones Encefálicas/fisiopatología , Niño , Traumatismos Craneocerebrales/sangre , Femenino , Escala de Coma de Glasgow , Humanos , Lenguaje , Imagen por Resonancia Magnética , Masculino , Memoria , Persona de Mediana Edad , Selección de Paciente , Estudios Prospectivos , Reproducibilidad de los Resultados , Factores de Tiempo , Tomografía Computarizada por Rayos XRESUMEN
Studies of cerebrospinal fluid (CSF) concentrations of neuron-specific enolase (NSE) in patients with neurological lesions indicate a quantitative relation between the degree of cell damage in the central nervous system (CNS) and the concentration of this CNS-specific protein. We collected serum and CSF from 63 males and 24 females undergoing various surgical procedures in spinal anaesthesia. The patients had no actual or previous history of neurological disease. The mean value of NSE in serum was 7.1 +/- 3.6 micrograms/L. NSE concentrations in CSF demonstrated age- and sex-dependency, with an increase with age from 21 to 84 years and significantly higher levels in males than in females. Therefore, age- and sex-matched reference values have to be used when NSE is evaluated in CSF in patients with different neurological disorders.
Asunto(s)
Sistema Nervioso/enzimología , Fosfopiruvato Hidratasa/sangre , Fosfopiruvato Hidratasa/líquido cefalorraquídeo , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Envejecimiento/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso , Valores de Referencia , Análisis de Regresión , Distribución por SexoAsunto(s)
Traumatismos Craneocerebrales/sangre , Proteína S/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Estudios de Casos y Controles , Niño , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Factores de TiempoRESUMEN
The present study has confirmed that human colostrum contains a lactoperoxidase (EC 1.11.1.7) [Langbakk & Flatmark (1984) FEBS Lett. 174, 300-303], which represents about 0.004% of the total protein in crude colostrum. An apparent 32-fold purification of the enzyme was obtained by a multistep procedure, as modified from that of the bovine enzyme, with a recovery of about 7%. By use of chromatography on an immunoaffinity column (directed against bovine lactoperoxidase B), an apparent 1450-fold purification was obtained in a single step, with a recovery of 21%. The enzyme behaved as a glycoprotein (binding to concanavalin A-Sepharose), and revealed spectral properties (Soret peak at 412 nm) and an Mr (80,000) similar to those of the bovine enzyme.
Asunto(s)
Calostro/enzimología , Lactoperoxidasa/aislamiento & purificación , Peroxidasas/aislamiento & purificación , Cromatografía de Afinidad , Cromatografía Líquida de Alta Presión , Electroforesis en Gel de Poliacrilamida , Femenino , Humanos , Técnicas de Inmunoadsorción , Embarazo , RadioinmunoensayoRESUMEN
A peroxidase with stability, chromatographic and immunoreactive properties similar to that of bovine lactoperoxidase has been partly purified from human colostrum. Hydrophobic interaction chromatography on Phenyl-Sepharose C1-4B gave a 10-fold purification with an apparent recovery of about 45%. The enzyme was quantitatively and specifically adsorbed to beads of anti-lactoperoxidase (bovine)-Protein A-Sepharose. No adsorption of the enzyme was observed on immunoadsorbent columns prepared with high-titre polyclonal antibodies raised against human myeloperoxidase and human eosinophile peroxidase.