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1.
J Hypertens ; 18(9): 1327-30, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10994764

ABSTRACT

OBJECTIVE: Gordon's syndrome comprises hypertension, hyperchloremic acidemia, hyperkalemia and intact renal function. We hypothesize that disturbances of one or more cell membrane ion carriers, handling sodium, chloride and potassium, might be relevant in this disorder and, furthermore, that such disturbances might be related to altered.cell membrane composition. DESIGN AND METHODS: In a patient diagnosed with Gordon's syndrome, we assessed the kinetics (K(m) and maximal rate) of four membrane sodium transport systems in sodium-enriched erythrocytes, according to the technique of Garay. We also measured the lipid composition of erythrocyte membrane in this patient and 69 essential hypertensive controls, using the latroscan technique. RESULTS: Compared to reference values of patients with essential hypertension, this patient exhibited a marked increase in the maximal rate of the Na+-K+-2Cl(-)-cotransport (964.0 micromol/l per cell versus the 391.6 +/- 222 micromol/l per cell in essential hypertensives). Also, there was an increased concentration of erythrocyte membrane phosphatidylethanolamine and a reduced concentration of sphingomyelin (27.9 and 11.1% versus 17.9 +/- 3.8% and 18.2 +/- 3.4%, respectively). CONCLUSIONS: We conclude that this abnormality in membrane Na+-K+-2Cl- cotransport could be responsible for the hyperkalemia, hyperchloremic acidemia and increased reabsorption of sodium observed in this condition and, furthermore, that such disturbance in membrane cotransport might be related to altered phospholipid concentration in cell membranes.


Subject(s)
Carrier Proteins/metabolism , Erythrocyte Membrane/metabolism , Hypertension/metabolism , Phosphatidylethanolamines/metabolism , Pseudohypoaldosteronism/metabolism , Sphingomyelins/metabolism , Adolescent , Humans , Hyperkalemia/metabolism , Male , Sodium-Potassium-Chloride Symporters
2.
Ann Nutr Metab ; 43(2): 113-20, 1999.
Article in English | MEDLINE | ID: mdl-10436310

ABSTRACT

BACKGROUND: A decreased content of n-3 fatty acids in erythrocyte membrane of type 1 diabetic patients, which is inversely related to plasma levels of HbA(1c), has been reported previously. Our aim in this study was to observe the changes after a low-dose n-3 fatty acid (330 mg/day docosahexaenoic acid and 630 mg/day eicosapentanoic acid) dietary intervention in the lipid composition of cell membrane and metabolic control (measured according to plasma HbA(1c) levels). Since changes in both parameters may alter transmembrane sodium transport or influence parameters measuring target organ damage, we also studied the neural conduction quality and activity of four sodium transporters. METHODS: Eighteen type 1 diabetic patients were randomly assigned to continue their usual diet (control group) or to supplement their diet with a daily low dose of n-3 fatty acids (supplemented group). The changes between baseline and end values of the following parameters were compared: HbA(1c), lipid and phospholipid composition of cell membrane, activity of four ion carriers and neural conduction quality. RESULTS: The dietary supplementation caused statistically significant changes in membrane lipid composition, particularly an increase of C22:6 (n-3) and the total n-3 fatty acid (respectively +0.90+/-1.14% vs. -0.44+/-1.23% and +1.36+/-1.62% vs. -0.5+/-1.80%, p<0.05). After the dietary supplementation, we also observed a significant decrease of HbA(1c) (-2.00+/-1.9% vs. -0.13+/-0.48%, p<0.05), without significant changes in the dose of insulin required, an increase in the motor conduction velocity by the median nerve (+2.12 +/-1.35 m/s vs. -0.8+/-2.34 m/s, p<0.05) and a decrease of the V(max) of the Na(+)-Li(+) countertransport (-96.6+/-111.2 vs. +58.1+/-81.3 micromol/l cell/h(-1), p<0.01). CONCLUSION: A low-dose omega-3 fatty acid dietary supplementation may change the fatty acid composition of the cell membrane and improve the metabolic control of diabetes. Using this dose, we also observed a decrease of the maximal rate of Na(+)-Li(+) countertransport and a slight improvement of neural conduction.


Subject(s)
Diabetes Mellitus, Type 1/diet therapy , Membrane Lipids/analysis , Neural Conduction/physiology , Sodium/metabolism , Adolescent , Adult , Biological Transport/physiology , Blood Glucose , Body Mass Index , C-Peptide/analysis , Cholesterol/blood , Diabetes Mellitus, Type 1/pathology , Diabetes Mellitus, Type 1/physiopathology , Erythrocytes/chemistry , Fatty Acids/blood , Fatty Acids, Omega-3/administration & dosage , Fatty Acids, Omega-3/blood , Fatty Acids, Omega-3/therapeutic use , Female , Hemoglobin A/analysis , Humans , Insulin/therapeutic use , Male , Prospective Studies
3.
Med Clin (Barc) ; 112(18): 699-701, 1999 May 22.
Article in Spanish | MEDLINE | ID: mdl-10374203

ABSTRACT

BACKGROUND: Porphyria cutanea tarda (PCT) is characterized by a deficiency of uroprophyrinogen decarboxylase (URO-D). The activity of this enzyme is decreased in the presence of iron-dependent disorders. A relationship between the hepatic hemosiderosis, which is present in most patients with PCT, and the status of the hemochromatosis gene has been observed. Particularly, two mutations of the gene have been described, one of them (Cys282Tyr) is related to the iron overload and might influence on the development of the clinical signs of PCT. PATIENTS AND METHODS: We have measured the transferrin saturation percentage and observed the status of the hemochromatosis gene in a patient diagnosed with PCT and in five of their relatives. RESULTS: The proband and one sister had a marked increase of uroporphyrins and iron overload, and both had the mutation Cys282Tyr, which was also present in the mother. CONCLUSIONS: This is the first study measuring iron overload and hemochromatosis gene mutations in relatives, and not in patients with PCT. We think that the study of this family justifies the systematic investigation of these parameters in all first degree relatives of patients with PCT, to identify subjects at risk, who can benefit from prophylactic measures and early therapy.


Subject(s)
Hemochromatosis/genetics , Porphyria Cutanea Tarda/genetics , Adult , Exons/genetics , Female , HLA Antigens/genetics , Humans , Male , Middle Aged , Pedigree , Point Mutation/genetics , Polymerase Chain Reaction , Porphyrins/blood , Porphyrins/urine , Transferrin/genetics
4.
Blood Press ; 5(1): 50-6, 1996 Jan.
Article in English | MEDLINE | ID: mdl-8777474

ABSTRACT

In essential hypertensive patients "exaggerated natriuresis" is a response to acute volume expansion. However, the underlying mechanisms for this remain to be determined. We studied 19 patients with essential hypertension (HP) and 9 normotensive subjects (NS). In all examined subjects the response to acute central volume expansion, without the plasma compositional change that Trendelenburg's position involves, was evaluated during 90 min (period T) after a similar period of deambulation (period D). Mean blood pressure (MBP), tubular sodium handling by the lithium clearance technique, plasma renin activity (PRA), plasma aldosterone (PA), plasma catecholamines and urine prostaglandine E2 and kallikrein were assessed after D and T. MBP was significantly higher in HP than in NS (p = 0.00001). HP showed "exaggerated natriuresis" after T (fractional excretion of sodium increased from 0.55 +/- 0.1% after D to 1.20 +/- 0.2% after T, p < 0.01). This was because of a decrease in their proximal fractional reabsorption of sodium (from 74.96 +/- 1.8% after D to 62.50 +/- 2.8% after T, p < 0.01). Plasma epinephrine and plasma dopamine after T were significantly lower than in standing position in HP (p < 0.01) but no in NS. The decrease in plasma renin activity after T in HP was 53%, and 32% in NS. There were not any significant differences between groups in the other neurohormonal systems studied. We conclude that the major determinant of "exaggerated natriuresis" in hypertensive patients is a higher stimulation of the cardiopulmonary receptors following Trendelenburg's position and consequently stronger reflex inhibition of sympathetic system activity and renin-angiotensin II activity. The "exaggerated natriuresis" after Trendelenburg's position in HP was an expression of abnormal pressure natriuresis.


Subject(s)
Head-Down Tilt , Hypertension/metabolism , Kidney Tubules/metabolism , Sodium/metabolism , Adult , Aldosterone/blood , Body Mass Index , Dinoprostone/urine , Epinephrine/blood , Female , Humans , Kallikreins/urine , Male , Norepinephrine/blood , Renin/blood , Sodium/urine , Supine Position
5.
J Hypertens ; 12(12): 1383-6, 1994 Dec.
Article in English | MEDLINE | ID: mdl-7706698

ABSTRACT

OBJECTIVE: To determine whether the cholesterol distribution is impaired in erythrocyte membranes of normo- and hypercholesterolaemic patients with untreated essential hypertension. DESIGN: Observational case-control study. METHODS: Erythrocytes were prepared from venous blood samples obtained from normotensive subjects and hypertensive patients. The membrane cholesterol distribution was measured by cholesterol oxidation to cholestenone after continuous cholesterol oxidase treatment. The membrane cholesterol content was determined. The ability of cells to be labelled with [3H]-cholesterol was also tested. RESULTS: The cholesterol distribution was asymmetric in erythrocyte membranes of the control subjects, and hypertensive patients. The oxidation rate was faster in normotensive subjects, and no differences were found between normo- and hypercholesterolaemic hypertensive patients. Total cholesterol mass was lower in erythrocyte membranes of hypertensive patients, as indicated by a higher incorporation of radioactive cholesterol. CONCLUSION: These data suggest that the membrane cholesterol distribution is impaired in patients with untreated essential hypertension, and support the presence of cholesterol-rich domains in the erythrocyte membrane inner monolayer.


Subject(s)
Cholesterol/blood , Erythrocyte Membrane/chemistry , Hypertension/blood , Adult , Case-Control Studies , Cholesterol/metabolism , Female , Humans , Male , Middle Aged , Oxidation-Reduction
6.
Diabetologia ; 36(9): 850-6, 1993 Sep.
Article in English | MEDLINE | ID: mdl-8405757

ABSTRACT

We have studied the fatty acid composition of erythrocyte membrane phospholipids in nine Type 1 (insulin-dependent) diabetic patients and nine healthy control subjects. Cell membranes from the diabetic patients showed a marked decrease in the total amount of polyunsaturated fatty acids (19.0% +/- 2.2 vs 24.6% +/- 1.4, p < 0.0001) mainly at the expense of docosahexaenoic acid C22:6(n3) (2.9% +/- 1.1 vs 5.3% +/- 1.3, p < 0.001), and arachidonic acid C20:4n6 (12.0% +/- 1.6 vs 15.1% +/- 0.6, p < 0.0005). Conversely, the total amount of saturated fatty acids was significantly increased (p < 0.05) and the polyunsaturated/saturated ratio was decreased in the Type 1 diabetic patients (p < 0.00 005). Neither the time from diagnosis, nor C-peptide levels, correlated with parameters indicating a poor metabolic control of Type 1 diabetes. However, C22:6(n-3) and total n-3 content significantly correlated with HbA1c (r = -0.79 and r = -0.88, respectively, p < 0.01), fructosamine (r = -0.71 and r = -0.74, respectively, p < 0.05), and Na+-K+ ATPase activity (maximal rate/Km quotient) (r = 0.78 and r = 0.71, respectively, p < 0.05). In conclusion we have found marked alterations of cell membrane lipid composition in Type 1 diabetic patients. These cell membrane abnormalities in lipid content were related to sodium transport systems and to poor metabolic control. Either diet, or the diabetic state, might be responsible for the observed cell membrane abnormalities. A dietary intervention study might differentiate the role of diet and diabetes in the reported cell membrane alterations.


Subject(s)
Diabetes Mellitus, Type 1/blood , Erythrocyte Membrane/metabolism , Fatty Acids/blood , Membrane Lipids/blood , Phospholipids/blood , Sodium/blood , Adult , Biological Transport , Cholesterol/blood , Erythrocyte Membrane/chemistry , Fatty Acids/analysis , Fatty Acids, Unsaturated/analysis , Fatty Acids, Unsaturated/blood , Female , Humans , Lipoproteins, HDL/blood , Lipoproteins, LDL/blood , Male , Phospholipids/chemistry , Reference Values , Sodium-Potassium-Exchanging ATPase/blood
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