In vitro effects of verapamil and methoxy-verapamil [D 600] on transmembrane sodium and potassium transport in human erythrocytes.
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Biomedical subjects
Publications and source records attributed to F Quarello.
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The authors present the results of a simultaneous assay of: intracellular Na+ and K+ concentrations, Na+ and K+ outward bumetanide-sensitive effluxes (Na+, K+ cotransport), Na+ efflux stimulated by extracellular Li+ (Na+, Li+ countertransport), and ouabain- and bumetanide-resistant Na+ and K+ effluxes (passive membrane permeability) performed in red blood cells from 15 uremic patients an regular hemodialysis and from 12 normal subjects, with an established flux assay. Na+ and K+ effluxes by the Na+, K+ cotransport system were significantly (p less than 0.01) lower in uremic patients then in normals (219 +/- 37 vs 82 +/- 17 mumol/l RBC/h and 251 +/- 29 vs 139 +/- 14 mumol/l RBC/h respectively). In normal subjects the bumetanide sensitive Na+ and K+ effluxes were strongly (r = 0.89; p less than 0.01) intercorrelated; and the intracellular Na+ concentration was related to the outward Na+ cotransport flux (r = 0.53; p approximately 0.05). Among uremic patients these correlations were not found. Na+ and K+ intracellular concentrations, passive Na+ and K+ permeability, and Na+, Li+ countertransport activity were not different among uremic patients and normal controls. In conclusion, in uremic dialyzed patients, red blood cell Na+, K+ cotransport activity is quite uniformly suppressed. The possible pathogenesis of this disfunction is still speculative and deserves further studies.
The effects of a 2 litre intravenous infusion of saline (0.9% NaCl solution) over 3 h on erythrocyte transmembrane sodium transport were studied in 12 normal human subjects. After saline infusion a significant (P less than 0.01) reduction of both outward Na+,K+ pump- and Na+,K+ cotransport-mediated Na+ effluxes was observed. The Na+,Li+ countertransport rate and the passive Na+ permeability did not change. The incubation of the subjects' erythrocytes, obtained on a separate occasion, with their own plasma taken after the saline infusion, induced an inhibition of both Na+,K+ pump and Na+,K+ cotransport outward sodium fluxes. The percentage decrease after incubation was closely correlated with the percentage reduction induced by the saline infusion in vivo (r = 0.93 for the pump and r = 0.96 for cotransport; P less than 0.01). These data suggest that extracellular fluid volume expansion affects the release of circulating factors modulating sodium transport by the Na+,K+ pump and by Na+,K+ cotransport.
The acute effects of both acetate and bicarbonate hemodialysis on erythrocyte transmembrane sodium fluxes were investigated in 15 patients with chronic uremia. We observed a significance (p less than 0.01) stimulation of the Na+,K+ pump in both procedures, with a significant correlation to the amount of fluid removed during hemodialysis (r = 0.56, p less than 0.03). Outward Na+ cotransport fluxes significantly rose (p less than 0.05) after acetate hemodialysis and decreased (p less than 0.05) after bicarbonate hemodialysis. Minor and not significant pre- and posthemodialysis bidirectional changes were observed as regards the intraerythrocyte Na+ and K+ concentration, passive Na+ and K+ permeability, and Na+,Li+ countertransport. Hemodialysis may acutely affect the erythrocyte sodium pump and cotransport fluxes, possibly through the modulation of hormonal factors triggered by the extracellular volume changes.
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Peripheral and peritoneal lymphocytes were assayed by numerical tests in adults on peritoneal dialysis. T lymphocytes were classified by monoclonal antibodies (OKT3, OKT4, OKT8) and B lymphocytes by the presence of surface immunoglobulins, using the immunofluorescence technique. Peripheral T cells showed no significant change from the normal, except for T suppressor cells which increased in patients with 2 or more peritonitis episodes. Examination of peritoneal lymphocytes showed a significant reduction in S-IgA lymphocytes (B cells bearing IgA receptors) and an increase in T-suppressor cells (OKT8+) in patients who developed peritonitis in the follow-up study. The implications of these results are discussed with particular reference to susceptibility to peritonitis.
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A longitudinal analysis of blood pressure was performed in 30 patients on hemodialysis for at least 10 years, in order to clarify the long-term outcome of hypertension in dialysis patients. Before the start of the dialysis treatment 22 (73.3%) patients were hypertensive, while, after 10 years, only 5 (16.6%) were still hypertensive. Body weight tended to decrease progressively throughout the period of observation. Hypertension disappeared in the younger patients while it remained/appeared in those who were order showing the characteristics of systolic hypertension. Except for hematocrit no significant differences in metabolic findings were found between normotensive and hypertensive patients. ECG abnormalities were found to be more frequent after 10 years of dialysis than before the start of treatment. High blood pressure tends to disappear progressively in hemodialysis patients and to be no longer a problem in long-term survivors.
32 patients (22 biopsed) with lupus nephritis (LN) were observed for circulating immune complexes (IC). Solid phase C1q (SPC1q) and polyethylene glycol (PEG) precipitation tests were used. The patients were studied during the clinical follow-up in different phases of disease activity. Comparative studies between each histological class of LN and corresponding forms of idiopathic glomerulonephritis (IGN) were made: no significant differences were found between either mesangial LN and stalk mesangial IGN, or between focal proliferative LN an focal proliferative IGN. However, a significant difference was found for SPC1q data between diffuse proliferative LN and mesangiocapillary IGN, and between membranous LN and membranous IGN. LN, with an acute nephritic syndrome and hypocomplementemia, displayed SPC1q data significantly above the levels of IC found in IGN with similar clinical features. IC serum data would seem an important element for the diagnosis and the clinical management of patients affected by LN.
To evaluate the immunological state in chronic renal insufficiency, the Authors studied cellular and humoral immunity in 292 patients with chronic renal failure. They were divided into 3 groups: 1) 37 with creatinine clearance between 50 and 20 ml/min; 2) 57 with creatinine clearance between 20 and 8 ml/min; 3) 178 treated by hemodialysis. In vivo and in vitro tests, that is DNCB, PPD skin tests, spontaneous, active and EAC rosettes, surface membrane immunoglobulin test, complement (C3, C4) and serum immunoglobulins were taken as markers of the immune response. Cell-mediated immunity was found to be significantly impaired in patients with terminal renal insufficiency or on hemodialysis and also markedly reduced in patients with non-terminal renal insufficiency. Humoral immunity produced less significant results: the B lymphocyte count and serum immunoglobulins were normal; only C3 levels were found below normal range. Thus it would seem that cell-mediated immunodeficiency appears in an early stage of chronic renal failure and that hemodialysis does not improve this deficiency.
To evaluate the effect of transfusion on immunity, 14 uraemic patients treated with 3 blood transfusions from a single donor, at weekly intervals, were studied: in 5 cases HLA-A,B were compatible, in 9 cases they were not. As markers of cellular and humoral immunity DNCB, PPD skin tests, spontaneous and active E-rosettes, EAC-rosettes, surface membrane immunoglobulins, C3, C4, C3d, serum immunoglobulins, circulating immune complexes and C-reactive protein were investigated. This protocol was applied before transfusions, 1 week after each transfusion (day +7, +14, +21) and 20 weeks later (day +80). Before transfusions 8/14 patients were DNCB negative; both spontaneous and active E-rosettes were below normal range. The other parameters were normal. On day +7 T and B lymphocytes were increased, while the other parameters were unmodified. On day +21 there was a significant reduction (p less than 0.5) in T lymphocytes in patients treated with compatible transfusions. On day +80 3/3 DNCB positive patients, treated with compatible transfusions, became negative and 1/3 DNCB positive patients, treated with random transfusions, also became negative. Three/fourteen patients showed a decrease in B lymphocytes. The other results were unchanged. Our preliminary results suggest that transfusions, either from an HLA compatible donor or not, can impair lymphocyte function.
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Together with other forms of self-dialysis (including limited assistance and self-service), home dialysis keeps down cost to much lower levels than those ruling within the hospital. Self-management, which is a common factor of various types of extra-hospital dialysis, also enables the patient to fit in better to society and, in the majority of cases, offers complete working rehabilitation by way of deeper consciousness of his disease and of the various treatments for it. Personal experience of home dialysis covering 6 years activity in the sector is reported. 91 patients have been trained in self-management and 65 of these have already been sent home or are about to be. The most important problems tackled over this period are examined and the experience analysed. Particular reference is made to clinical, organizational and management problems. The paper thus forms a practical guide for those wishing to direct their efforts towards a home dialysis programme.
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