Martin Buysschaert

Cytochrome P4502E1 (CYP2E1) expression in peripheral blood lymphocytes: evaluation in hepatitis C and diabetes

ObjectiveCytochrome P4502E1 (CYP2E1) is expressed in human peripheral blood lymphocytes (PBLs), and previous reports have suggested the possibility of using this readily available tissue as a reporter of CYP2E1 status. To further explore the relevance of this approach we assessed CYP2E1 expression in PBLs in two contrasting conditions, chronic hepatitis C and insulin-dependent diabetes (IDD), illustrating an organ and a systemic disease, respectively.MethodsTotal RNA was isolated from extracted PBLs (hepatitis C patients + IDD) and by percutaneous needle biopsy (hepatitis C patients only). Gene expression for CYP2E1 was determined by real-time reverse-transcription polymerase chain reaction. Histological changes in liver tissue were assessed according to Ludwigs criteria.ResultsIn patients with chronic hepatitis C a clear relationship was found between CYP2E1 expression in the liver and the progression of hepatic disease (both lobular inflammation and fibrosis indices), and observed variations were consistent with the preferential distribution of CYP2E1 in the lobular zone. No effect of the liver disease was, however, found at the PBL level. A statistically significant increase in mean CYP2E1 expression level was observed in the lymphocytes from poorly controlled IDD subjects compared to controls.ConclusionsTaken together, our data indicate that the measurement of CYP2E1 expression in PBLs is not useful in liver diseases. However, in a systemic condition (IDD) this measurement can be proposed for monitoring the CYP2E1 induction in a relatively noninvasive manner. This tool should therefore be further validated in clinical field or experimental studies for CYP2E1 phenotyping purposes.

Effect of exercise on plasma atrial natriuretic factor and cardiac function in men and women.

Abstract In order to provide an integrated view of the physiology of atrial natriuretic factor (ANF) during exercise, we studied changes of its plasma concentrations in 13 normal subjects (seven males, six females) during three graded exercise levels and two periods of recovery (5 and 30 min), concomitantly with an assessment of cardiac function and ventricular volumes by multigated radionuclide angiography. Mean ANF levels (± SEM) increased in all patients at the second (P < 0·002) and third (P < 0·002) exercise levels, and after 5‐min recovery (P < 0·01): in males from 16 ± 7 to 30 ± 11 pg ml‐1at the third level, in females from 27 ± 12 to 61 ± 33 pg ml‐1. Normal values were observed after 30‐min recovery. Even if mean ANF levels were all higher in females, this difference did not reach statistical significance (P= 0·06). Significant decreases of ventricular volumes, as well as increases of ejection fraction and rate pressure product, were noted during exercise and were similar in both sexes. The kinetics of plasma ANF concentrations, compared with the increase of rate pressure product, was characterized by a latency and a remanence in recovery. This remanence, also present in the changes of ventricular volumes, supports the hypothesis that other factor(s) like catecholamines might still exert their influence after the exercise stops.

Effect of beta-adrenergic blockade on plasma atrial natriuretic factor and cardiac volumes during exercise in normal men.

Abstract Exercise stimulates the release of the atrial natriuretic factor (ANF). 1–3 The principal determinant of ANF release is atrial distension, 4 although adrenergic stimulation has also been implicated in the direct release of ANF. 5,6 Both of these mechanisms could account for the release of ANF during exercise. To elucidate the relative roles of these mechanisms, we determined the plasma ANF concentrations and cardiac volumes during exercise before and after β-adrenergic blockade with propranolol.