0000000000117825
AUTHOR
José M. Rodrigo
Plasma concentrations of nitric oxide and asymmetric dimethylarginine in human alcoholic cirrhosis.
The liver plays a prominent role in the metabolism of asymmetric dimethyl-l-arginine (ADMA), an endogenous inhibitor of nitric oxide (NO) synthase. This study was designed to determine whether plasma levels of ADMA and NO production are altered in patients with compensated and decompensated alcoholic cirrhosis.Plasma levels of l-arginine, ADMA, symmetric dimethylarginine (SDMA) and NO (nitrite plus nitrate, NOx) were measured in nine patients with compensated alcoholic cirrhosis (Child-Pugh A) and 11 patients with advanced cirrhosis (Child-Pugh B-C). Seven healthy volunteers served as controls.ADMA and NOx concentrations in decompensated cirrhosis were higher than in the compensated group a…
Value of the critical flicker frequency in patients with minimal hepatic encephalopathy
Minimal hepatic encephalopathy (MHE) is mainly diagnosed using psychometric tests such as the psychometric hepatic encephalopathy score (PHES). Despite the clinical and social relevance of MHE, psychometric testing is not widespread in routine clinical care. We assessed the usefulness of the critical flicker frequency (CFF), for the diagnosis of MHE and for the prediction of the development of overt episodes of HE. The normal range of PHES in the Spanish population was evaluated in a control group. Subsequently, 114 patients with cirrhosis and 103 healthy controls underwent both PHES and CFF tests. A diagnosis of MHE was made when the PHES was lower than −4 points. Patients were followed-up…
Metabolic profile of chronic liver disease by NMR spectroscopy of human biopsies.
Among the different processes occurring during the evolution of liver disease, fibrosis has a predominant role. Liver fibrosis mechanisms are fairly constant irrespective of the underlying etiology. Cirrhosis is the end-stage of this reaction. Metabolic profiles, which are affected by many physiological and pathological processes, may provide further insight into the metabolic consequences of this severe liver disease. The aim of this study was to demonstrate the applicability of 1H high resolution magic angle spinning (HR-MAS) NMR spectroscopy in the biochemical profile determination of human liver needle biopsy samples for the characterization of metabolic alterations related to the sever…
Mitochondrial oxidative stress and CD95 ligand: A dual mechanism for hepatocyte apoptosis in chronic alcoholism
Apoptosis plays an important role in the progression of alcohol-induced liver disease to cirrhosis. Oxidative stress is an early event in the development of apoptosis. The major aim of this study was to study the conditions in which oxidative stress occurs in chronic alcoholism and its relationship with apoptosis of hepatocytes. We have found that oxidative stress is associated with chronic ethanol consumption in humans and in rats, in the former independently of the existence of alcohol-induced liver disease. Ethanol or acetaldehyde induces apoptosis in hepatocytes isolated from alcoholic rats, but not in those from control rats. Inhibition of aldehyde dehydrogenase, but not of cytochrome …
A single transient episode of hyperammonemia induces long-lasting alterations in protein kinase A.
A single transient episode of hyperammonemia induces long-lasting alterations in protein kinase A. Am J Physiol Gastrointest Liver Physiol 292: G305-G314,2007; doi:10.1152/ajpgi.00100.2006.-Hepatic encephalopathy in patients with liver disease is associated with poor prognosis. This could be due to the induction by the transient episode of hepatic encephalopathy of long-lasting alterations making patients more susceptible. We show that a single transient episode of hyperammonemia induces long-lasting alterations in signal transduction. The content of the regulatory subunit of the protein kinase dependent on cAMP (PKA-RI) is increased in erythrocytes from cirrhotic patients. This increase is…
Focal cortical damage parallels cognitive impairment in minimal hepatic encephalopathy
Little attention has been paid to cortical integrity in patients with minimal hepatic encephalopathy (MHE), although cognitive functions affected in early stages of liver disease are mainly allocated in different neocortical structures. Here we used cortical surface-based analysis techniques to investigate if patterns of cortical thinning accompany the mildest form of HE. To aim this goal, cortical thickness obtained from high-resolution 31 magnetic resonance imaging (MRI) was measured in patients with no MHE (NMHE), MHE, and healthy controls. Further correlation analyses were performed to examine whether scores in the critical flicker frequency (CFF) test, and blood ammonia levels accounte…
Patients with minimal hepatic encephalopathy show impaired mismatch negativity correlating with reduced performance in attention tests
Attention deficit is an early event in the cognitive impairment of patients with minimal hepatic encephalopathy (MHE). The underlying mechanisms remain unclear. Mismatch negativity (MMN) is an auditory event-related potential that reflects an attentional trigger. Patients with schizophrenia show impaired attention and cognitive function, which are reflected in altered MMN. We hypothesized that patients with MHE, similarly to those with schizophrenia, should show MMN alterations related with attention deficits. The aims of this work were to assess whether (1) MMN is altered in cirrhotic patients with MHE, compared to those without MHE, (2) MMN changes in parallel with performance in attentio…
Metabolite identification in human liver needle biopsies by high-resolution magic angle spinning1H NMR spectroscopy
High-resolution magic angle spinning (HR-MAS) 1 H NMR spectroscopy of intact human liver needle biopsies has not been previously reported. HR-MAS NMR spectra collected on 17 specimens with tissue amounts between � 0.5 and 12 mg showed very good spectral resolution and signal-to-noise ratios. One-dimensional 1 H spectra revealed many intense signals corresponding to cellular metabolites. In addition, some high molecular weight metabolites, such as glycogen and mobile fatty acids, could be observed in some spectra. Resonance assignments for 22 metabolites were obtained by combining the analysis of three different types of 1D 1 H spectral editing, such as T2 filtering or the nuclear Overhauser…
Increased protein kinase A regulatory subunit content and cGMP binding in erythrocyte membranes in liver cirrhosis
Abstract Background/Aims : Patients with liver disease show increased plasma cGMP and decreased intracellular cGMP in lymphocytes. The initial aim of this work was to assess whether decreased intracellular cGMP and increased plasma cGMP may be due to increased ATP-dependent release of cGMP from cells. The results obtained led to a new aim: to identify and quantify a protein responsible for the increased cGMP binding found in erythrocyte membranes from patients with liver disease. Methods : ATP-dependent cGMP transport was determined in inside-out vesicles from erythrocyte membranes. cGMP-binding proteins were isolated from the membranes and identified by MALDI-TOF peptide mass fingerprint. …
Pegylated alpha-interferon-2a plus ribavirin compared with pegylated alpha-interferon-2b plus ribavirin for initial treatment of chronic hepatitis C virus: prospective, non-randomized study.
Background and aim We assessed whether the two regimens of pegylated alpha-interferon-2b (PEG-IFN-alpha2b) plus ribavirin and pegylated alpha-interferon-2a (PEG-IFN-alpha2a) plus ribavirin showed differences in terms of sustained virological response, withdrawal due to side-effects and dose adjustment requirements in the treatment of naive chronic hepatitis C virus (HCV) patients. Methods A prospective non-randomized, open-label comparison was made of naive HCV-infected patients undergoing standard 24- or 48-week treatment with two PEG-IFN combined with weight-based dosing regimen of ribavirin (PEG-IFN-alpha2a/ribavirin, n = 91; PEG-IFN-alpha2b/ribavirin, n = 92). Results Sustained virologi…
Accumulation of Symmetric Dimethylarginine in Hepatorenal Syndrome
In patients with cirrhosis, nitric oxide (NO), asymmetric dimethylarginine (ADMA), and possibly symmetric dimethylarginine (SDMA) have been linked to the severity of the disease. We investigated whether plasma levels of dimethylarginines and NO are elevated in patients with hepatorenal syndrome (HRS), compared with patients with cirrhosis without renal failure (no-HRS). Plasma levels of NO, ADMA, SDMA, and l-arginine were measured in 11 patients with HRS, seven patients with no-HRS, and six healthy volunteers. SDMA concentration in HRS was higher than in no-HRS and healthy subjects (1.47 ± 0.25 vs. 0.38 ± 0.06 and 0.29 ± 0.04 μM, respectively; P < 0.05). ADMA and NOx concentrations were…
Changing prevalence, clinical features, and outcome of acute hepatitis in Spain (1982-2003)
Background: Diagnostic and preventive measures have contributed to a change in the epidemiology of acute hepatitis. The purpose of the present paper was to assess the changing prevalence of acute hepatitis from 1982 to 2003. Methods: Trends in the epidemiology, clinical findings, and outcome of acute viral hepatitis from 1982 to 2003 were examined. A total of 548 episodes of acute hepatitis diagnosed between 1982 and 2003, the clinical course of which was monitored up to the year 2003, were included. Annual changes as well as for the intervals 1982–1992 and 1993–2003 were compared. Results: Severe infections occurred in 1.3% of cases, with a mortality of 0.6%, with progression into chron…
Serum malondialdehyde: possible use for the clinical management of chronic hepatitis C patients
Serum lipid peroxidation products are increased in inflammatory liver disease and, as we previously reported, also in chronic hepatitis C. We have performed a specific assay of malondialdehyde, the reported most abundant product of lipid peroxidation, in serum of twenty four chronic hepatitis C patients, before, during, and after interferon treatment. Liver biopsies were performed in each patient before and after interferon treatment. The results show higher serum malondialdehyde values in chronic hepatitis C patients than healthy subjects (n = 68) before interferon treatment (p < .001). Mean value of serum malondialdehyde levels after interferon treatment was significantly lower than befor…
Correlation of nitric oxide and atrial natriuretic peptide changes with altered cGMP homeostasis in liver cirrhosis.
: Background: Cyclic GMP (cGMP) concentration is increased in plasma of patients with liver cirrhosis. Three possible mechanisms may contribute: increased cGMP synthesis by soluble (activated by nitric oxide), or particulate (activated by atrial natriuretic peptide (ANP)) guanylate cyclase or increased release from cells. Aim: The aim of this work was to analyze the possible contributors to increased plasma cGMP and to assess whether changes in the parameters of the system vary with the degree of liver disease (Child Pugh score) or by the presence of ascites. Methods: We measured cGMP in plasma and lymphocytes, soluble guanylate cyclase activation by nitric oxide in lymphocytes, nitrates an…