ABSTRACT
BACKGROUND: Chronic liver diseases are frequently complicated by portal hypertension, an important component of which is the increased intrahepatic vascular resistance, in part related to endothelial dysfunction. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, is an established mediator and marker of endothelial dysfunction. We therefore investigated the possible implication of ADMA in chronic liver diseases-induced portal hypertension. MATERIALS AND METHODS: We studied 39 consecutive patients with compensated hepatitis C virus (HCV) related chronic liver diseases. All patients underwent hepatic venous pressure gradient (HVPG) measurement, and simultaneous blood sampling from the hepatic vein and the pulmonary artery, for ADMA and nitrite/nitrate (NOx) plasma level determinations. RESULTS: A positive correlation between HVPG and ADMA concentrations in hepatic veins (ADMA-h) was found (r = 0.77, P < 0.0001). Moreover, a negative correlation between HVPG and NOx concentrations in the hepatic veins (NO-h) (r = -0.50, P = 0.005), and between ADMA-h and NO-h was observed (r = -0.40, P = 0.02). ADMA concentrations in pulmonary artery (ADMA-p) (0.55 +/- 0.13 micromol L(-1)) were significantly higher than in hepatic veins (0.47 +/- 0.09 micromol L(-1)) (P < 0.0001). CONCLUSIONS: These results suggest that ADMA may play a pathophysiological role in portal hypertension by contributing to the relative intrahepatic NO deficiency typical of endothelial dysfunction.
Subject(s)
Arginine/analogs & derivatives , Hepatitis C, Chronic/complications , Hypertension, Portal/etiology , Liver Cirrhosis/physiopathology , Adult , Aged , Arginine/physiology , Case-Control Studies , Female , Hepatitis C, Chronic/physiopathology , Humans , Hypertension, Portal/physiopathology , Male , Middle Aged , Nitric Oxide/metabolism , Portal Pressure/physiologyABSTRACT
BACKGROUND: Perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) have been regarded as a possible immunogenetic marker of ulcerative colitis. If this were true, the p-ANCA status of a given patient should be constant over time; however, little information is available on this issue. METHODS: One hundred and forty-five sera collected from 40 ulcerative colitis patients during a mean follow-up period of 50.6 months were tested for p-ANCA reactivity by indirect immunofluorescence. RESULTS: At base line 24 patients (60%) were p-ANCA-positive, with no relationship to gender distribution, age at diagnosis, disease activity, or extension. During follow-up, changes in p-ANCA status occurred in 10 patients (25%). P-ANCA positivity during follow-up was associated with more aggressive forms of disease, whereas p-ANCA negativity was associated with stable remission. CONCLUSIONS: Changes in the p-ANCA status over time occur in some ulcerative colitis patients. P-ANCA behaviour is associated with different clinical patterns of disease.
Subject(s)
Antibodies, Antineutrophil Cytoplasmic/blood , Colitis, Ulcerative/immunology , Adolescent , Adult , Colitis, Ulcerative/pathology , Female , Fluorescent Antibody Technique, Indirect , Humans , Longitudinal Studies , Male , Middle AgedABSTRACT
BACKGROUND: Antineutrophil cytoplasmic antibodies (ANCAs) from patients with vasculitidis can induce neutrophils to release oxygen radicals in vitro. ANCAs with a perinuclear pattern of immunofluorescence are found in most patients with ulcerative colitis, but several findings are against ANCAs having a pathogenetic role in this disease. AIMS: To evaluate the influence of ANCAs associated with ulcerative colitis on the respiratory burst activity of neutrophils. PATIENTS: Serum samples were obtained from 14 patients with ulcerative colitis, seven of whom showed positivity for p-ANCAs, three patients with vasculitidis, two with positivity for p-ANCAs, and one for c-ANCAs, and seven healthy volunteers. METHODS: A positive ANCA serology was determined with a standard indirect immunofluorescence assay. Purified immunoglobulins (IgGs) were prepared from serum samples by DEAE-Affigel blue chromatography. Human neutrophils were prepared by dextran-Ficoll-Hypaque separation. Superoxide anion (O2-.) generation was measured by following the superoxide dismutase inhibitable reduction of ferricytochrome. RESULTS: There were no significant differences among samples from ulcerative colitis IgG p-ANCA positive, ulcerative colitis IgG p-ANCA negative patients, and controls on O2-. production, whereas ANCA positive IgG from vasculitidis significantly enhanced O2-. release (p < 0.001). CONCLUSIONS: p-ANCAs associated with ulcerative colitis have no effect on the respiratory burst activity of normal human neutrophils in vitro. These results reinforce the hypotheses that ANCAs are unlikely to contribute to the pathogenesis of ulcerative colitis.
