Good therapeutical response of Goodpasture's syndrome with severe renal failure.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
R Pontremoli
Publications and source records attributed to R Pontremoli.
Amino acid imbalance in patients with chronic renal failure.
Explore the source record for details and available documents.
Amino Acids↗
Characterization of the calpastatin defect in erythrocytes from patients with essential hypertension.
In erythrocytes of patients with essential hypertension the level of calpastatin activity was found to be significantly lower than in red cells of normotensive subjects (1). We now demonstrate, by Western blot analysis, that the decreased inhibitory activity is due to a corresponding decrease in the amount of the inhibitor protein. This is also supported by the observation that calpastatins isolated and purified from erythrocytes of normotensive and hypertensive patients, have identical specific activity. Data are presented indicating that the decreased level of calpastatin cannot be ascribed to an accelerated decay of the inhibitor during the erythrocyte life span. Taken together the previous and present results further emphasize that an umbalanced proteolytic system may represent one of the molecular mechanisms responsible for those membrane abnormalities underlying the development of essential hypertension and its clinical complications.
Antibodies, Monoclonal↗
The role of calpain in the selective increased phosphorylation of the anion-transport protein in red cell of hypertensive subjects.
The phosphorylation of the anion-transport protein (band 3) is selectively increased in human red cell membrane, following exposure of intact cells to ionophore and micromolar calcium. The phosphorylation is catalyzed by a membrane associated protein kinase distinct from either protein kinase C or Ca2+/calmodulin dependent protein kinase. We show that the increase in phosphorylation of band 3 is abolished if red cells had been pre-loaded with an inhibitor of calpain or with an anticalpain monoclonal antibody. Our findings suggest that calpain activity may control, both at a functional and at a structural level, the activity of this important transmembrane protein through the modulation of its susceptibility as a substrate of membrane bound protein kinase(s). Based on previous observations indicating the presence in erythrocytes from hypertensive patients of an uncontrolled intracellular calpain-mediated proteolytic system accompanied by an increased phosphorylation of band 3 protein(s), we suggest that our results may shed light on the type of molecular alteration which is associated with the hypertensive state.
Anion Transport Proteins↗
Erythrocyte deficiency in calpain inhibitor activity in essential hypertension.
The calpain-calpain inhibitor system was evaluated in erythrocytes of patients with essential hypertension and normotensive controls, either with or without a family history of hypertension. Calpain levels were similar in the controls and hypertensive patients, whereas the inhibitor activity level was significantly reduced in the latter (301.8 +/- 26.4 vs 220 +/- 14 U/mg hemoglobin, p less than 0.001). Borderline hypertensive patients and a few controls with a history of hypertension showed low inhibitor activity. Similar results have recently been reported in genetically hypertensive rats of the Milan strain. A significant inverse correlation (r = -0.43, p less than 0.001) was found between mean arterial pressure and calpain inhibitor. Although the pathophysiological significance of these observations is not yet clear, they suggest a new area of investigation into the molecular mechanisms underlying essential hypertension and its complications.
Adult↗
Increased phosphorylation in red cell membranes of subjects affected by essential hypertension.
In hemolysates of red cells from hypertensive patients the proteolytic activity of calpain is expressed at a rate approximately three fold higher than in red cells of normotensive subjects. Susceptibility to lysis upon exposure to ionophore A23187 and calcium, conditions that increase intracellular calpain activity, is also significantly enhanced in erythrocytes of hypertensive patients. In inside-out vesicles prepared from erythrocytes of these patients band 3 region undergoes a high extent of phosphorylation which is 1.5 fold higher than that occurring in control red cells from normotensive subjects. This increased phosphorylation can be reproduced in inside-out vesicles from erythrocytes of normal subjects following pretreatment with calpain. Taken together, these results suggest that the presence in erythrocytes of hypertensive subjects of an unregulated calpain dependent proteolytic activity may affect the structure of plasma membranes and determine an increased phosphorylation of intrinsic membrane proteins.
Anion Exchange Protein 1, Erythrocyte↗
Renal metabolism of amino acids in early insulin-dependent diabetes mellitus.
Renal metabolism of amino acids (AAs) was evaluated in 5 patients with early IDDM, and in 7 controls (C) in the basal state for 80 minutes after the ingestion of an AA mixture simulating an animal protein meal. Insulin was withdrawn 20 hours before the study. Renal metabolism of AAs was evaluated by the arterial-venous difference technique. In the basal state in IDDM, as in C, the kidney takes up large amounts of a few nonessential AAs (NEAAs): it releases many NEAAs and a few essential AAs (EAAs). After AA ingestion in C, renal extraction of most EAAs, mainly BCAAs, Lys, and Thr, occurs; Pro extraction also increases and a significant uptake of Gly, Glu, Asp, Orn, and Tyr takes place. EAA extraction accounts for 30-40% of total AA uptake. In IDDM, after AA ingestion, a) renal uptake of total AAs is significantly lower, owing mainly to a markedly lower uptake of BCAAs, Lys, and also of Pro, Orn, and Ala; b) renal EAA uptake accounts for less than 20% of total AA extraction. These results indicate that in IDDM postprandial renal N repletion is impaired and unbalanced.
Adult↗
Long term effect of nifedipine GITS and lisinopril on subclinical organ damage in patients with essential hypertension.
BACKGROUND: Preventing subclinical organ damage is currently a major issue in the management of patients with essential hypertension. Antihypertensive drugs which act through different pathophysiological mechanisms might confer specific target organ protection beyond what is already provided by their blood pressure lowering effect. METHODS: Thirty-one patients with essential hypertension were randomized to receive long-term treatment with either a calcium channel blocker (nifedipine GITS, 90 mg/day) or an ACE-inhibitor (lisinopril, 20 mg/day). Blood pressure, left ventricular mass, carotid wall thickness and timed urinary albumin excretion were measured at baseline and over the course of 24 months of treatment. RESULTS: Both regimens significantly lowered mean blood pressure over the 24 months (from 124+/-2 to 103+/-2 mmHg in the lisinopril group and from 122+/-2 to 104+/-1 in the nifedipine group). Overall, end-organ damage improved with persistent blood pressure control. However, the two treatments had different specific effects. Lisinopril induced a more pronounced reduction of the left ventricular mass index (from 56+/-3 to 52+/-2 g/m2.7, P< 0.05) and urinary albumin excretion (from 34+/-15 to 9+/-2 microg/min, P< 0.01), while nifedipine achieved a greater reduction of carotid intima plus media thickness (from 0.8+/-0.06 to 0.6+/-0.06 mm, P< 0.01). CONCLUSIONS: Blood pressure control does help reduce the severity of organ damage in patients with essential hypertension. Different antihypertensive treatments may confer additional specific cardiorenal and vascular protection regardless of blood pressure control. These data could be useful when devising individualized therapeutic strategies in high-risk hypertensive patients.
Angiotensin-Converting Enzyme Inhibitors↗