Ammonia : this is not the end but rather the end of the beginning

Hepatic encephalopathy (HE) represents a wide spectrum of neurological or neuropsychological symptoms caused by liver disease and/or portosystemic shunts. The major role of hyperammonemia in association with systemic inflammation and oxidative stress in the pathogenesis of HE has progressively emerged. However, the cascading downstream effects caused by these pathogenic factors remain unresolved. The underlying abnormalities which are thought to cause HE include modification of glutamatergic and GABAergic neurotransmission, mitochondrial dysfunction, energy impairment, lactate dyshomeostasis, increased blood-brain barrier permeability, brain edema/astrocyte swelling, as well as accumulation of toxic compounds (manganese, bile acids, indols)

Brain edema : a valid endpoint for measuring hepatic encephalopathy?

Hepatic encephalopathy (HE) is a major complication of liver failure/disease which frequently develops during the progression of end-stage liver disease. This metabolic neuropsychiatric syndrome involves a spectrum of symptoms, including cognition impairment, attention deficits and motor dysfunction which eventually can progress to coma and death. Pathologically, HE is characterized by swelling of the astrocytes which consequently leads to brain edema, a common feature found in patients with acute liver failure (ALF) as well as in cirrhotic patients suffering from HE. The pathogenic factors involved in the onset of astrocyte swelling and brain edema in HE are unresolved. However, the role of astrocyte swelling/brain edema in the development of HE remains ambiguous and therefore measuring brain edema as an endpoint to evaluate HE is questioned. The following review will determine the effect of astrocyte swelling and brain edema on neurological function, discuss the various possible techniques to measure brain edema and lastly to propose a number of neurobehavioral tests to evaluate HE

Progressive resistance training prevents loss of muscle mass and strength in bile duct‐ligated rats

BACKGROUND: Loss of muscle mass and strength is common in cirrhosis and increases the risk of hyperammonaemia and hepatic encephalopathy. Resistance training optimizes muscle mass and strength in several chronic diseases. However, the beneficial effects of resistance training in cirrhosis remain to be investigated. Bile duct-ligated (BDL) rats develop chronic liver disease, hyperammonaemia, reduced muscle mass and strength. Our aim was to test the effects of resistance training on muscle mass, function and ammonia metabolism in BDL-rats. METHODS: A group of BDL-rats underwent a progressive resistance training programme and a group of non-exercise BDL-rats served as controls. Resistance training comprised of ladder climbing with a progressive increase in carrying weights attached to the tail. Training was performed 5 days a week during 4 weeks. Muscle strength and body composition were assessed using grip strength and EchoMRI. Weight and circumference of the gastrocnemius muscle (normalized to bodyweight), plasma ammonia and glutamine synthetase protein expression and activity were assessed. RESULTS: BDL + exercise rats had significantly larger gastrocnemius circumference compared to non-exercise BDL-rats: ratio 0.082 vs 0.075 (P < 0.05). Gastrocnemius muscle weight was higher in exercisers than controls: 0.006 vs 0.005 (P < 0.05). A tendency towards a lower plasma ammonia in the exercise group compared to controls was observed (P = 0.10). There were no differences in lean body mass, GS protein expression and activity between the groups. CONCLUSION: Resistance training in rats with chronic liver disease beneficially effects muscle mass and strength. The effects were followed by non-significant reduction in blood ammonia; however, a tendency was observed

Psychometric Properties and Validation of the EMOTICOM Test Battery in a Healthy Danish Population.

Disruptions in hot cognition, i.e., the processing of emotionally salient information, are prevalent in most neuropsychiatric disorders and constitute a potential treatment target. EMOTICOM is the first comprehensive neuropsychological test battery developed specifically to assess hot cognition. The aim of the study was to validate and establish a Danish language version and reference data for the EMOTICOM test battery. To evaluate the psychometric properties of 11 EMOTICOM tasks, we collected data from 100 healthy Danish participants (50 males, 50 females) including retest data from 49 participants. We assessed test-retest reliability, floor and ceiling effects, task-intercorrelations, and correlations between task performance and relevant demographic and descriptive factors. We found that test-retest reliability varied from poor to excellent while some tasks exhibited floor or ceiling effects. Intercorrelations among EMOTICOM task outcomes were low, indicating that the tasks capture different cognitive constructs. EMOTICOM task performance was largely independent of age, sex, education, and IQ as well as current mood, personality, and self-reported motivation and diligence during task completion. Overall, many of the EMOTICOM tasks were found to be useful and objective measures of hot cognition although select tasks may benefit from modifications to avoid floor and ceiling effects in healthy individuals

Proteome Analysis of Pod and Seed Development in the Model Legume Lotus japonicus

Legume pods serve important functions during seed development and are themselves sources of food and feed. Compared to seeds, the metabolism and development of pods are not well-defined. The present characterization of pods from the model legume Lotus japonicus, together with the detailed analyses of the pod and seed proteomes in five developmental stages, paves the way for comparative pathway analysis and provides new metabolic information. Proteins were analyzed by two-dimensional gel electrophoresis and tandem-mass spectrometry. These analyses lead to the identification of 604 pod proteins and 965 seed proteins, including 263 proteins distinguishing the pod. The complete data set is publicly available at http://www.cbs.dtu.dk/cgi-bin/lotus/db.cgi, where spots in a reference map are linked to experimental data, such as matched peptides, quantification values, and gene accessions. Identified pod proteins represented enzymes from 85 different metabolic pathways, including storage globulins and a late embryogenesis abundant protein. In contrast to seed maturation, pod maturation was associated with decreasing total protein content, especially proteins involved in protein biosynthesis and photosynthesis. Proteins detected only in pods included three enzymes participating in the urea cycle and four in nitrogen and amino group metabolism, highlighting the importance of nitrogen metabolism during pod development. Additionally, five legume seed proteins previously unassigned in the glutamate metabolism pathway were identified