A cytoplasmic antigen associated to inosine-5'-monophosphatedehydrogenase 2 eliciting specific antibodies (antirods and rings, RR) has been identified in patients with chronic hepatitis C who were exposed to pegylated interferon (PI) and ribavirin (RBV). The significance of anti-RR in these patients merits to be investigated. Sera from 88 chronic hepatitis C virus (HCV)-infected patients undergoing PI-RBV therapy were analysed for the presence of RR pattern by indirect immunofluorescence on HEp-2 substrate (Inova Diagnostics, San Diego, CA, USA). Anti-RR antibodies developed de novo in 32 patients independently of any demographic and virological feature, but with a significant association with cumulative exposure to PI-RBV (P = 0.0089; chi-square test). RR pattern was significantly more frequent in relapsers than in patients achieving sustained virological response (56% vs 30%; P = 0.0282, chi-square test). Anti-RR titre ranged from 1:80 to 1:1280, but significantly declined following treatment cessation. Anti-RR develop de novo in a substantial proportion of patients exposed to PI-RBV in relation to the duration of treatment exposure. Further investigations are necessary to unravel the mechanisms leading to the formation of these autoantibodies.
This is the first study defining the reference range for serum CT in the pediatric population and large enough to be statistically meaningful. Our proposal may facilitate the process of decision making when dealing with gene carriers of MEN 2.
Rationale: Septic patients have typically reduced concentrations of hemoglobin and albumin, the major components of non-carbonic buffer power(β). This could expose patients to high pH variations during acid-base disorders. Objectives: To compare, in-vitro, non-carbonic β of septic patients with that of healthy volunteers, and evaluate its distinct components. Methods: Whole blood and isolated plasma of 18 septic patients and 18 controls were equilibrated with different CO2 mixtures. Blood gases, pH and electrolytes were measured. Non-carbonic β and non-carbonic β due to variations in Strong Ion Difference (βSID) were calculated for whole blood. Non-carbonic β and non-carbonic β normalized for albumin concentrations (βNORM) were calculated for isolated plasma. Representative values at pH=7.40 were compared. Albumin proteoforms were evaluated via two-dimensional electrophoresis. Measurements and Main Results: Hemoglobin and albumin concentrations were significantly lower in septic patients. Septic patients had lower non-carbonic β both of whole blood (22.0±1.9 vs. 31.6±2.1 mmol/L, p<0.01) and plasma (0.5±1.0 vs. 3.7±0.8 mmol/L, p<0.01). Non-carbonic βSID was lower in patients (16.8±1.9 vs. 24.4±1.9 mmol/L, p<0.01) and strongly correlated with hemoglobin concentration (r=0.94, p<0.01). Non-carbonic βNORM was lower in patients (0.01 [-0.01 - 0.04] vs. 0.08 [0.06 - 0.09] mmol/g, p<0.01). Septic patients and controls showed different amounts of albumin proteoforms. Conclusions: Septic patients are exposed to higher pH variations for any given change in CO2 due to lower concentrations of non-carbonic buffers and, possibly, an altered buffering function of albumin. In both septic patients and healthy controls, electrolyte shifts are the major buffering mechanism during respiratory acid-base disorders.
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