Cognitive function in patients with alcoholic and nonalcoholic chronic liver disease.

The aim of the present study was to characterize the neurophysiological profile of cognitive impairment associated with patients with chronic alcoholic and nonalcoholic liver disease. The authors evaluated 43 patients with cirrhotic liver disease: 19 patients with chronic alcohol ingestion and 24 nonalcoholic patients who had been infected with hepatitis B or C virus. Eleven healthy subjects were included as control subjects.

Bile acids content in brain of common duct ligated rats.

Introduction: Cholestasis leads to liver cell death, fibrosis, cirrhosis, and eventually liver failure. Bile duct ligated rats constitute an interesting model to study the mechanism of cholestasis, and its action on several organs and tissues, including the brain.

Aim: To analyze brain bile acids individually in ligated rats to evaluate if its profile is altered towards a more toxic condition in cholestasis.

Hepatic encephalopathy: An approach to its multiple pathophysiological features.

Hepatic encephalopathy (HE) is a neuropsychiatric complex syndrome, ranging from subtle behavioral abnormalities to deep coma and death. Hepatic encephalopathy emerges as the major complication of acute or chronic liver failure. Multiplicity of factors are involved in its pathophysiology, such as central and neuromuscular neurotransmission disorder, alterations in sleep patterns and cognition, changes in energy metabolism leading to cell injury, an oxidative/nitrosative state and a neuroinflammatory condition.

Mitochondrial dysfunction as a mediator of hippocampal apoptosis in a model of hepatic encephalopathy.

In this study, we describe the presence of apoptosis, associated with a mitochondrial dysfunction in the hippocampus of animals in an experimental model defined as minimal hepatic encephalopathy (MHE). This experimental model was studied after 10 days of induced portal vein calibrated stricture, leading to portal hypertension and to a moderate hyperammonemia, without the presence of other evident central nervous system changes. The molecular mechanisms here proposed indicate the presence of apoptotic intrinsic pathways that point to hippocampal mitochondria as an important mediator of apoptosis in this experimental model.

Glutamine synthetase activity and glutamate uptake in hippocampus and frontal cortex in portal hypertensive rats.

Aim: To study glutamine synthetase (GS) activity and glutamate uptake in the hippocampus and frontal cortex (FC) from rats with prehepatic portal vein hypertension.

Methods: Male Wistar rats were divided into sham-operated group and a portal hypertension (PH) group with a regulated stricture of the portal vein. Animals were sacrificed by decapitation 14 d after portal vein stricture.

Hepatic encephalopathy, ammonia, glutamate, glutamine and oxidative stress.

This review addresses recent and not so recent works that emphasize on the mechanisms by which liver damage can induce encephalopathy. Hepatic encephalopathy constitutes an intriguing complication in severe liver acute and chronic disease, whose pathophysiology is still not completely understood. In this pathology, alterations in normal brain function are associated with morphological and functional impairments of astrocytes and neurons.

Reyes's syndrome, encephalopathy, hyperammonemia and acetyl salicylic acid ingestion in a city hospital of Buenos Aires, Argentina.

Twelve cases of Reye's syndrome are presented with different degrees of encephalopathy, hyperammonemia and hypoglycemia; associated to acetyl salicylic acid (ASA) ingestion. The aim of the present retrospective study was to describe our experience in selected patients with Reye's syndrome associated to the ASA ingestion and to underline the influence of hyperammonemia on Reye's encephalopathy. All the cases presented moderate hyperbilirubinemia, elevated alanine aminotransferase, aspartate aminotransferase with an average of 302+/-205 UI/L and 285+/-149 UI/L respectively.

Oxidative stress and hippocampus in a low-grade hepatic encephalopathy model: protective effects of curcumin.

Aim: The present study was performed on prehepatic portal hypertensive rats, a model of low-grade hepatic encephalopathy, designed to evaluate whether oxidative stress was a possible pathway implicated in hippocampal damage and if so, the effect of an anti-oxidant to prevent it.

Methods: Prehepatic portal hypertension was induced by a regulated portal vein stricture. Oxidative stress was investigated by assessing related biochemical parameters in rat hippocampus.

Enzymatic activities in brains of diabetic rats treated with vanadyl sulphate and sodium tungstate.

The hypothesis of the present study was that diabetes mellitus might affect brain metabolism. Streptozotocin (STZ)-induced diabetic rats, treated with vanadyl sulphate (V) and sodium tungstate (T) were employed to observe the aspartate aminotransferase (AST), alanine aminotransferase (ALT) and creatine kinase (CK) activities in brain homogenates. Significant increases in AST, ALT and CK activities were found in diabetic brain homogenates against controls, suggesting increments of transamination in brain and/or increases in cell membrane permeability to these enzymes.

Involvement of serum apolipoprotein AI and B100 and lecithin cholesterol acyl transferase in alcoholic cirrhotics.

Lipoproteins are synthesized by the liver and secreted to plasma. Chronic alcoholic intoxication produces frequently cirrhosis and concomitantly alterations in liver metabolism. Thirty patients with alcoholic cirrhosis and 83 healthy controls were selected for this study.

Altered blood-brain barrier permeability in rats with prehepatic portal hypertension turns to normal when portal pressure is lowered.

Aim: To study the blood-brain barrier integrity in prehepatic portal hypertensive rats induced by partial portal vein ligation,at 14 and 40 d after ligation when portal pressure is spontaneously normalized.

Methods: Adult male Wistar rats were divided into four groups: Group I: Sham14d , sham operated; Group II: PH14d , portal vein stenosis; (both groups were used 14 d after surgery); Group III: Sham40d, Sham operated and Group IV: PH40d Portal vein stenosis (Groups II and IV used 40 d after surgery). Plasma ammonia,plasma and cerebrospinal fluid protein and liver enzymes concentrations were determined.

Bile acid profiles by capillary electrophoresis in intrahepatic cholestasis of pregnancy.

ICP (intrahepatic cholestasis of pregnancy) is characterized by pruritus and biochemical cholestasis, including raised SBAs (serum bile acids) and, usually, elevated aminotransferases levels. However, AHP (asymptomatic hypercholanaemia of pregnancy) is defined as the presence of total SBA levels above the cut-off value (11 microM) in healthy pregnant women, thus elevation of total SBAs do not necessarily reflect an ICP condition. The aim of the present study was to describe clinical, obstetric, perinatal and biochemical findings, as well as the SBA profile, in pregnant women studied in the third trimester of pregnancy in order to define characteristic patterns of individual bile acids that enable women with ICP to be distinguished from AHP and healthy pregnancies.

Lack of Supervision and Independent Clinical Decision Making in Postgraduate Pediatric training in Australia.

Objective: Evaluation of postgraduate pediatric training is a complex yet critical task. We aimed to review pediatric trainees' attitudes to clinical decision-making, levels of supervision and end of life issues in a tertiary pediatric teaching hospital in Sydney, Australia.

Method: A questionnaire was devised and distributed to all trainees at Sydney Children's Hospital, Randwick.

Hepatic morphological changes and oxidative stress in chronic streptozotocin-diabetic rats.

Oxidative stress (OS) is a biological entity quoted as responsible for several pathologies including diabetes. Diabetes mellitus (DM) has been also associated to human cirrhosis. The present work was designed to study the occurrence of OS as well as morphologic alterations in rat livers following induction of DM.

Hippocampal mitochondrial dysfunction with decreased mtNOS activity in prehepatic portal hypertensive rats.

Portal hypertension is a major complication of human cirrhosis that frequently leads to central nervous system dysfunction. In our study, rats with prehepatic portal hypertension developed hippocampal mitochondrial dysfunction as indicated by decreased respiratory rates, respiratory control and mitochondrial nitric oxide synthase (mtNOS) activity in mitochondria isolated from the whole hippocampus. Succinate-dependent respiratory rates decreased by 29% in controlled state 4 and by 42% in active state 3, and respiratory control diminished by 20%.

Role of heme oxygenase/carbon monoxide pathway on the vascular response to noradrenaline in portal hypertensive rats.

1. Portal hypertension (PH), a major syndrome in cirrhosis, producing hyperdynamic splanchnic circulation and hyperaemia. In order to elucidate the contribution of heme oxygenase to the vascular hyporeactivity, we assessed the activity of heme oxygenase-1 (HO-1), measured the in vivo pressure response to noradrenaline (NA) and investigated the effects of blocking the carbon monoxide (CO) and nitric oxide (NO) pathways in a prehepatic model of PH in rats.

Hyperammonemia, brain edema and blood-brain barrier alterations in prehepatic portal hypertensive rats and paracetamol intoxication.

Aim: To study the blood-brain barrier integrity, brain edema, animal behavior and ammonia plasma levels in prehepatic portal hypertensive rats with and without acute liver intoxication.

Methods: Adults male Wistar rats were divided into four groups. Group I: sham operation; II: Prehepatic portal hypertension, produced by partial portal vein ligation; III: Acetaminophen intoxication and IV: Prehepatic portal hypertension plus acetaminophen.

Decreased oxidative stress in prehepatic portal hypertensive rat livers following the induction of diabetes.

1. Oxidative stress (OS) is a biological entity indicated as being responsible for several pathologies, including diabetes. Diabetes can also be associated with human cirrhosis.

Does hepatomegaly alter iron-dependent oxidative effects in human plasma?

A four-fold increase in the iron content of normal subjects was detected in plasma after 5 hours of iron administration. Iron supplementation had a surprisingly erratic effect on four patients with hepatomegaly secondary to heart insufficiency, since the increase in the iron content in the plasma after iron-dextran administration was either within the control range or significantly lower, independently of the initial values. Thiobarbituric acid reactive substances (TBARS) content was 2.

[Functional alterations in central nervous system of prehepatic portal hypertensive rats].

Prehepatic Portal Hypertension (PH) leads to morphologic changes in the rat Central Nervous System, including alterations of the blood brain barrier (BBB), and astrogliosis and angiogenesis in CA1 and CA4 hyppocampal fields. The present study investigates functional changes in portal hypertensive rats. Wistar Kyoto rats were used (240 g/bw) and allotted in two groups: GI (n = 8) portal hypertensive rats obtained through a regulated stenosis of the portal vein (Groszmann), and GII (n = 6), sham-operated rats.

[Does TNF-alpha contribute to liver disease physiopathology?].

The aim of the present paper is to establish the possible role of serum TNF in the pathophysiology of three experimental models of liver injury: paracetamol intoxication, cholestasis followed by paracetamol intoxication and cholestasis. We concluded that under our experimental conditions the serum TNF-alpha levels were not responsible for the inflammatory phenomena described in our previous paper as apoptosis.

Drug glucuronidation and hepatic lipid microsomal membrane profile in cholestatic rats followed paracetamol intoxication.

The uridin-diphosphoglucuronyl-transferase (UDP-GT) is a membrane-bound enzyme responsible for glucuronidation of endogenous and exogenous compounds. This work established the UDP-GT activity and its lipid membrane microenvironment in two experimental models: acute paracetamol intoxication, and cholestasis followed by acute paracetamol intoxication. Cholestasis was performed by bile duct ligation.

[Benzodiazepines metabolism in various models of experimental liver diseases].

The aim of the present paper is to establish possible disturbances in benzodiazepines glucuronidation in two experimental models of liver injury: paracetamol acute intoxication and cholestasis followed by paracetamol acute intoxication. We concluded that, despite the alterations observed in liver microsomal lipid profile, glucuronidation remained similar to controls in paracetamol intoxicated rats. On the contrary, cholestatic animals followed by paracetamol intoxication showed an increment in the glucuronidation of the utilized substrated.