Optiminzación del diagnóstico y tratamiento de la insuficiencia hepática aguda en Pediatría / Optimizing the diagnosis and treatment of acute liver failure in pediatrics

La insuficiencia hepática aguda en pediatría (IHAP) es una entidad poco, pero muy grave, que puede causar la muerte del paciente o requerir trasplante hepático en un 25-40% de los casos. Distinguir aquellos pacientes con IHAP que van a requerir un trasplante de aquellos que regenerarán con tratamiento médico sigue siendo unr eto para el hepatólogo e intensivista. Desafortunadamente, los sistemas de categorización utilizados en pacientes adultos no predicen correctamente la supervivencia libre de trasplante en pediatría. En nuestro centro, utilizamos el aclaramiento de verde de indocianina como herramienta para catalogar los pacientes afectos de una IHAP que requerirán un trasplante hepático. Según nuestra experiencia, el valor que marcaría la necesidad de trasplantar un pacient sería menor de 5,9%/min don una sensibilidad de 91,6% y una especificidad de 96,8%. Asimismo, en el contexto de una IHAP, los sitemas de asistencia hepática extracorpórea como el MARS (Molecular Adsorbent Recirculating System) pueden servir para comprar tiempo para la regeneración del hígado nativo como puente al trasplante disminuyendo el riesgo de complicaciones cerebrales hasta en pacientes con hígados completamente necróticos (AU)

Pediatric acute liver failure (p-ALF) is a rare disorder wich results in death or the need for liver transplantation (LT) in 25-40% of cases. Distinghishing the children with p-ALF who require LT from those patients who will likely survive with intensive medical care alone remains a unclear making a challenge the decision of when to transplant a patient. The scoring systems availables for prognosis evaluation in adult are unable to predict survival without LT of pediatric patient. Un our hostpial we use the indocyanine green plasma disapparance rate as a tool to precit the evolution of pediatric patients with acute liver failure. Following our experience, a cutoff value of ICG-PDR of 5,9% /min has 91,6% sensitiviry and 96,8% specificity for assessing the need for liver transplantation, improving the categorization of patients with pediatric acute liver failure. In the setting of actue live failure, extracorporeal liver assist devices like MARs (Molecular Adsorbent Recirculating System) may buy time for native liver recovery or serve as bridging therapy to liver transplantation, with reduced risk of cerebral complications, MARS treatment may alleviate hepatic encephalopathy even in patients with a completely necrotic liver (AU)

Effects of cocaine administration on VTA cell activity in response to prefrontal cortex stimulation.

The repeated use of psychostimulants in humans has been associated with progressive enhancement of anxiety, panic attacks, and eventually paranoid psychosis. The appearance of such behaviors has been termed behavioral sensitization, which forms part of the basic pathological mechanisms involved in drug addiction. Psychostimulants act via a circuit involving the ventral tegmental area (VTA), prefrontal cortex (PFC), and nucleus accumbens. The PFC sends glutamatergic projections that activate dopaminergic neurons in the VTA. These projections provide an extremely important excitatory drive necessary for the development of sensitization. The effects of cocaine administration on the response of dopaminergic VTA cells to activation of the PFC have not been reported. Here the effects of acute cocaine administration on VTA cell response to PFC stimulation are examined. Statistical analysis of the changes in spontaneous activity and evoked response revealed a significant decrease in spontaneous activity at 1.0 mg/kg i.v. after cocaine treatment compared to baseline levels. The net effect was an increase in signal-to-noise ratio. Treatment with MK-801 at a dose of 2 mg/kg showed that the excitatory response was, at least partially, NMDA-mediated. Prazosin pretreatment (0.5 mg/kg i.p.) did not prevent a significant decrease in spontaneous activity brought about by cocaine (15 mg/kg, i.p.). Nonetheless, prazosin alone induced a significant decrease in the response to PFC stimulation when compared to baseline. In addition, iontophoretic application of norepinephrine (NE) onto VTA cells revealed that NE potentiated (19.2%), enhanced (26.9%), or suppressed (46.2%) the glutamate-evoked response in VTA cells. The results suggest that a possible role of cocaine in the process of sensitization might be to amplify the PFC-induced excitation at the VTA. Since the iontophoretic release of NE in almost half of the sampled cells produced similar effects to those of cocaine it may suggest a possible NE-mediated mechanism for cocaine actions.

Effects of intravenous cocaine administration on cerebellar Purkinje cell activity.

The goal of the present study was to investigate the effects of intravenous cocaine administration on cerebellar Purkinje cell firing. Extracellular neuron activity was recorded and cells were locally excited with spaced microiontophoretic pulses of glutamate. Glutamate-evoked and spontaneous discharges were compared before and immediately following cocaine administration. Cocaine injections (1. 0 and 0.25 mg/kg, i.v.) induced a reversible suppression of both spontaneous activity and glutamate-evoked excitation. Procaine was ineffective in producing similar actions. Cocaine only inhibited glutamate-induced excitation in animals pre-treated with reserpine (5 mg/kg, i.p.). Propranolol injections (10 mg/kg, i.p.) were ineffective in blocking cocaine-induced inhibitions. Yohimbine (5 mg/kg, i.p.) pre-treatment abolished cocaine-induced suppressions of either spontaneous or glutamate-evoked excitation. Therefore, cocaine administration decreases Purkinje cell spontaneous and glutamate-evoked discharges by a mechanism involving alpha(2)-adrenoceptor activation. It is suggested that by changing the normal function of the cerebellum cocaine can produce drug-related alterations in overt behavior and cognition.

Chronic imipramine treatment induces downregulation of alpha-2 receptors in rat's locus coeruleus and A2 region of the tractus solitarius.

Imipramine is an effective antidepressant agent that blocks the reuptake of monoamines. In order to understand some of its basic mechanisms of action, we investigated the effects of chronic imipramine administration (10 mg/kg, i.p.; 21 days) on the alpha-2 receptor population of several brain sites. Alpha-2 receptor density was estimated by in vitro autoradiography using [3H]Idazoxan. The densitometric analysis revealed a decreased receptor density in the A2 region of the tractus solitarius (20%) and locus coeruleus (16%). No changes were observed in the amygdala, pyriform cortex, periacueductal gray and the bed nucleus of the stria terminalis. These results suggest that chronic imipramine treatment selectively modulates the alpha-2 receptor population localized in the brain stem norepinephrine-rich nuclei and not in the population present on limbic structures innervated by noradrenergic terminal projections. The possible physiological consequences of this selective modulation of alpha-2 receptors are discussed.