Document Detail


Activation of soluble guanylate cyclase by nitric oxide in lymphocytes correlates with minimal hepatic encephalopathy in cirrhotic patients.
MedLine Citation:
PMID:  17216205     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Patients with liver cirrhosis with normal neurological and mental status examination may present minimal forms of hepatic encephalopathy, showing intellectual function impairment that cannot be detected through general clinical examination but can be unveiled using specific neuropsychological or neurophysiological examination. Evaluation of minimal hepatic encephalopathy (MHE) in cirrhotic patients would have prognostic value. The psychometric hepatic encephalopathy score (PHES) has been recommended as the "gold standard" in the diagnosis of MHE. Altered modulation of cyclic GMP (cGMP) levels in the brain seems to be responsible for the impairment of some types of cognitive function in liver disease. In animal models of liver disease, some of the alterations in modulation of cGMP levels in the brain are reproduced in lymphocytes. The aim of the present work was to assess whether there is a correlation between the alterations in different parameters involved in modulation of cGMP levels and the presence of MHE in patients with liver disease. We studied in 46 patients with liver cirrhosis and 26 controls the performance in the PHES battery of psychometric tests and the critical flicker frequency (CFF), the concentration of cGMP in plasma and lymphocytes, activation of guanylate cyclase by nitric oxide (NO) in lymphocytes, and several parameters likely involved in altered cGMP homeostasis in liver disease such as ammonia, NO metabolites, and atrial natriuretic peptide (ANP). Activation of guanylate cyclase by NO in lymphocytes and cGMP in plasma were higher and CFF lower in patients with MHE than in patients without MHE. Ammonia, ANP, and metabolites of NO were higher in patients than in controls but were no different in patients with or without MHE. Alteration in activation of guanylate cyclase by NO in lymphocytes correlates with PHES performance, CFF, and ammonia levels. This suggests that altered modulation of guanylate cyclase by NO in lymphocytes would reflect a parallel alteration in the brain occurring in patients with MHE that would be involved in their cognitive impairment.
Authors:
Carmina Montoliu; Blanca Piedrafita; Miguel A Serra; Juan A del Olmo; Antonio Ferrandez; José M Rodrigo; Vicente Felipo
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-01-10
Journal Detail:
Title:  Journal of molecular medicine (Berlin, Germany)     Volume:  85     ISSN:  0946-2716     ISO Abbreviation:  J. Mol. Med.     Publication Date:  2007 Mar 
Date Detail:
Created Date:  2007-02-19     Completed Date:  2008-01-24     Revised Date:  2011-07-08    
Medline Journal Info:
Nlm Unique ID:  9504370     Medline TA:  J Mol Med (Berl)     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  237-45     Citation Subset:  IM    
Affiliation:
Servicio de Hepatología, Departamento de Medicina, Hospital Clínico Universitario, Universidad de Valencia, Valencia, Spain.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Case-Control Studies
Cyclic GMP / blood
Enzyme Activation / drug effects
Female
Guanylate Cyclase / metabolism*
Hepatic Encephalopathy / blood,  complications*,  enzymology*
Humans
Liver Cirrhosis / complications*,  enzymology,  metabolism
Liver Failure / complications
Lymphocytes / enzymology*,  metabolism
Male
Middle Aged
Nitric Oxide / biosynthesis,  metabolism*
Nitric Oxide Donors / pharmacology
Penicillamine / analogs & derivatives,  pharmacology
Receptors, Cytoplasmic and Nuclear / metabolism*
Chemical
Reg. No./Substance:
0/Nitric Oxide Donors; 0/Receptors, Cytoplasmic and Nuclear; 0/S-nitro-N-acetylpenicillamine; 10102-43-9/Nitric Oxide; 52-67-5/Penicillamine; 7665-99-8/Cyclic GMP; EC 4.6.1.2/Guanylate Cyclase; EC 4.6.1.2/soluble guanylyl cyclase
Comments/Corrections
Comment In:
J Mol Med (Berl). 2007 Mar;85(3):203-5   [PMID:  17273819 ]

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