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Biomedical subjects

F Marchini

Publications and source records attributed to F Marchini.

At least 37 records · Page 2Linked to original sources
PubMed1996

The abnormal red-cell oxalate transport is a risk factor for idiopathic calcium nephrolithiasis: a prospective study.

An abnormal erythrocyte transmembrane oxalate flux was described in recurrent idiopathic calcium nephrolithiasis. To verify whether it might represent a risk marker of renal stone disease, two prospective studies were carried out. One hundred ninety patients with idiopathic calcium nephrolithiasis who were enrolled at their first episode of lithiasis during the period 1984 to 1986, form the basis of the first prospective study. The impact of erythrocyte oxalate transport anomaly, gender, familial occurrence of nephrolithiasis, hypercalciuria, hyperoxaluria, and hyperuricosuria on stone recurrence by both bivariate and multivariate analysis of frequencies was assessed. The predictive value of the erythrocyte anomaly for a patient's becoming a stone former was also assessed in five nephrolithiasis families. Recurrence occurred in 57.9% of patients; this was significantly associated with the erythrocyte anomaly, hyperoxaluria, and male gender. However, when using multivariate analysis, only gender and the erythrocyte anomaly were statistically significant and were independent predictors of recurrency. The probability of stone recurrency predicted by the logistic model ranged from 30.1% for women with normal erythrocyte oxalate transport, to 73.4% for men with the erythrocyte anomaly. The family follow-up showed that only subjects with the erythrocyte abnormality become renal stone-formers in the 8-yr survey. By showing the predictive value of the erythrocyte oxalate anomaly for recurrent calcium nephrolithiasis, our findings support the notion that this anomaly is a risk factor in renal stone disease.

Adolescent↗
PubMed1996

Anomalous phospholipid n-6 polyunsaturated fatty acid composition in idiopathic calcium nephrolithiasis.

Anomalies in the erythrocyte transport of anions and cations have been described in idiopathic calcium oxalate nephrolithiasis and seem to play a pathogenetic role in this disease. In consideration of the hypothesis that the complex array of ion flux cell abnormalities is an epiphenomenon of an anomaly in the composition of cell membranes, this study investigated cell-membrane lipid composition. In idiopathic calcium oxalate renal stone formers, in which ion transport abnormalities were present, and in healthy control subjects, plasma and erythrocyte membrane lipid composition, the erythrocyte oxalate exchange, and Na/K/2Cl cotransport activity were evaluated. Furthermore, in stone formers, the effect of a 30-day fish-oil diet supplementation on plasma lipids, erythrocyte oxalate exchange, oxaluria, and calciuria was investigated. The effect of archidonic acid released by phospholipase A2 on anion-carrier phosphorylation and activity in erythrocytes was evaluated as well. Patients had a lower content of linoleic and higher concentration of archidonic acids in both plasma and erythrocyte membrane phospholipids, and an increased archidonic/linoleic acid ratio. The archidonic acid level correlated with the erythrocyte oxalate exchange and sodium cotransport activity. Fish-oil supplementation lowered calcium and oxalate urine excretion, and normalized the erythrocyte oxalate exchange. Phospholipase A2 increased the erythrocyte anion-carrier protein phosphorylation and the oxalate exchange. This study shows that idiopathic calcium nephrolithiasis in the patient group reported here is characterized by a systemic defect in phospholipid archidonic acid levels that might provide an answer to the link between genetic background, dietary habits, and renal lithiasis.

Adult↗
PubMed1996

Z1046: a new specific peripheral dopaminergic compound.

It is well established that peripheral dopamine receptors activation evokes vasodilation and neurohormonal modulation. Z1046 is a potent mixed dopaminergic agonist and is highly selective over adrenergic and serotoninergic (5-HT2) activities. In contrast, dopamine had agonist activities on all adrenergic receptors while it is known that dopexamine has a beta 2 agonist activity and is an inhibitor of the neuronal uptake. As far as fenoldopam is concerned, selective stimulation of D1-like receptors leads to an increase of renin release. In conclusion, Z1046 is a potent and specific drug for dopamine receptors. This profile makes Z1046 different from other dopaminergic agents.

Animals↗
PubMed1995

The effect of selective phosphodiesterase inhibitors in comparison with other anti-asthma drugs on allergen-induced eosinophilia in guinea-pig airways.

The effects of isoenzyme selective phosphodiesterase (PDE) inhibitors and other anti-asthma drugs on antigen-induced eosinophil recruitment and activation in guinea-pig airways was studied. Guinea-pigs were sensitized and subsequently challenged with aerosolized ovalbumin (OVA). Bronchoalveolar lavage (BAL) was performed 24 h later. A significant increase in eosinophils and eosinophil peroxidase (EPO) was detected in BAL fluid and BAL fluid supernatant respectively from OVA immunized guinea-pigs compared with sham treated animals. Guinea-pigs were treated for 7 days prior to antigen challenge with either the following drugs or the appropriate vehicle (i.p.). The selective beta 2 agonist, salbutamol (0.3 mg/kg), the PDE III inhibitor, milrinone (15 mg/kg) and the non-selective PDE inhibitor, trequinsin (1 mg/kg) had no effect on eosinophil number or EPO levels. The PDE IV inhibitor, rolipram (15 mg/kg), the mixed type III/IV PDE inhibitor, benzafentrine (15 mg/kg) and the non-selective PDE inhibitor, aminophylline (31.5 mg/kg) had no effect on eosinophil number but reduced the amount of EPO detected. The anti-inflammatory glucocorticosteroids, beclomethasone (10 mg/kg) and betamethasone (4 mg/kg) and the type IV PDE inhibitor, RP 73401 (5 mg/kg) reduced both eosinophil numbers and EPO levels. These results suggest a role for the type IV PDE isoenzyme in the control of eosinophil recruitment and possibly activation in the airways.

Adrenal Cortex Hormones↗
PubMed1995

Characterization of big endothelin-1-induced contraction in rabbit saphenous artery.

We have characterized the endothelin-converting enzyme (ECE)-like activity involved in big endothelin (ET)-1-induced contraction in rabbit saphenous artery (RSA). Big ET-1 30 nM caused a contraction that was independent of the vascular endothelium. Phosphoramidon and the neutral endopeptidase (NEP) inhibitors thiorphan and candoxatrilat blocked the vasoconstriction caused by big ET-1 in endothelium-denuded RSA. Candoxatrilat (IC50 17 nM) and thiorphan (IC50 2.5 nM), were 5- to 30-fold more potent than phosphoramidon (IC50 83 nM). Other protease inhibitors were inactive. In cultured endothelial cells the ET-1 release was inhibited only by phosphoramidon (IC50 16 microM) but at a concentration 200-fold that required an endothelium-denuded RSA. In conclusion, we can speculate that the big ET-1 contraction in RSA is mediated by an ECE, probably present on smooth muscle cells, which is susceptible to NEP inhibitors and is different from the ECE on endothelial cells.

Animals↗
PubMed1994

Abnormal erythrocyte and renal frusemide-sensitive sodium transport in idiopathic calcium nephrolithiasis.

1. Anomalous transmembrane anion transport has been observed in erythrocytes of patients with idiopathic calcium nephrolithiasis. 2. To verify whether cation transport is also abnormal, we investigated the frusemide-sensitive Na+ efflux from Na(+)-loaded erythrocytes and the natriuretic response to acute intravenous frusemide administration in calcium oxalate renal stone formers. 3. Frusemide administration induced a statistically significant smaller increase in the fractional excretion of Na+ in patients than in control subjects. Abnormal kinetic properties of erythrocyte Na(+)-K(+)-2Cl- cotransport were observed in approximately 60% of stone formers. The Km for Na+ of Na(+)-K(+)-2Cl- co-transport correlated with urinary Ca2+ excretion. 4. The abnormal kinetic properties of Na(+)-K(+)-2Cl- co-transport may be relevant for stone formation, hampering renal Ca2+ reabsorption in the distal nephron and determining critical physicochemical conditions for calcium/oxalate crystallization.

Adult↗
PubMed1993

Abnormal urate transport in erythrocytes of patients with idiopathic calcium nephrolithiasis: a possible link with hyperuricosuria.

1. The demonstration of an inheritable anomaly of erythrocyte oxalate transport in 'primary' calcium nephrolithiasis suggested that this disease might be a generalized metabolic disorder characterized by a defect in cellular anion transport. 2. To determine whether this anomaly is restricted to oxalate alone, we studied erythrocyte transmembrane urate self-exchange in calcium-oxalate renal stone formers in whom urinary excretion of uric acid is frequently increased. 3. Abnormal urate self-exchange was found in 30% of the patients. The urate self-exchange rate constant was correlated with 24 h urinary excretion of uric acid; the erythrocyte anomaly was also associated with the frequency of hyperuricosuria and a more intense disease activity. Transmembrane urate self-exchange was inhibited by stilbene and heparan sulphate. Morphazinamide administration did not reduce urinary urate excretion in patients with abnormal urate erythrocyte self-exchange. 4. These findings suggest that hyperuricosuria during calcium-oxalate renal stone disease might be due to a cellular defect in urate transport, and further support the hypothesis that idiopathic nephrolithiasis is a metabolic disorder characterized by a defect in cellular anion transport.

Biological Transport↗
PubMed1991

Correction of erythrocyte abnormalities in idiopathic calcium-oxalate nephrolithiasis and reduction of urinary oxalate by oral glycosaminoglycans.

Calcium-oxalate nephrolithiasis is associated with a defect in erythrocyte oxalate self-exchange and an abnormal rate of erythrocyte membrane protein phosphorylation. There is evidence that glycosaminoglycans (GAGs) have a regulatory effect on both of these processes. This study tested the hypothesis that modifications of erythrocyte oxalate self-exchange induced by oral GAGs are paralleled by similar changes in overall oxalate metabolism. 40 patients with idiopathic calcium-oxalate nephrolithiasis were treated for 15 days with 60 mg/day of a mixture of GAGs. By day 15 of treatment there were significant reductions from baseline in erythrocyte oxalate self-exchange (mean [SD] 1.67 [1.18] vs 2.59 [1.63] x 10(2) per min; p less than 0.005) and erythrocyte membrane protein phosphorylation (55.8 [7.3] vs 72.9 [6.8] x 10(-3) cpm/mg protein; p less than 0.005), but also in urinary oxalate excretion (0.24 [0.09] vs 0.31 [0.15] mmol/24 h; p less than 0.005). This finding suggests similar changes in both erythrocytes and other cells more important in oxalate handling. The changes had reversed by 15 days after withdrawal of treatment. Acute intravenous administration of GAGs (60 mg) induced a fall in carbon-14-labelled oxalate renal clearance (143 [13] vs 169 [28] ml/min; p less than 0.005), which strongly suggests the participation of the kidney. However, reduced oxalate absorption from the intestine, and even decreased synthesis of oxalate, cannot be ruled out.

Administration, Oral↗
PubMed1991

Effects of the oral administration of glycosaminoglycans on cellular abnormalities associated with idiopathic calcium oxalate nephrolithiasis.

Oral administration of mixture of extractive glycosaminoglycans to a group of renal stone formers led to a significant decrease in oxalate self-exchange and in erythrocytes membrane protein phosphorylation traits that are abnormal in the majority of patients with idiopathic calcium nephrolithiasis. The action of glycosaminoglycans at the cellular level is probably due to their modulating activity on certain membrane protein kinases. The proven effect of the glycosaminoglycans opens a new pharmacological approach to the prevention of recurrent nephrolithiasis.

Administration, Oral↗
PubMed1990

Is hydrochlorothiazide-induced hypocalciuria due to inhibition of prostaglandin E2 synthesis?

1. Since prostaglandin E2 could play a role in idiopathic hypercalciuria, and considering the well-established hypocalciuric action of hydrochlorothiazide, we have evaluated the effect of 15 days' treatment with hydrochlorothiazide in 10 hypercalciuric male stoneformers on urinary Ca2+ and prostaglandin E2, as well as on plasma bicyclo-prostaglandin E2, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and parathyroid hormone. 2. In addition to lowering urinary Ca2+ (P less than 0.001), hydrochlorothiazide also promoted a significant fall in urinary prostaglandin E2 (P less than 0.001), plasma bicyclo-prostaglandin E2 (P less than 0.001) and 1,25-dihydroxyvitamin D (P less than 0.01), and an increase in plasma parathyroid hormone (P less than 0.025), whereas plasma 25-hydroxyvitamin D was unchanged. 3. A positive correlation between urinary Ca2+ and prostaglandin E2 was present before (P less than 0.00005), but not after, hydrochlorothiazide. Plasma bicyclo-prostaglandin E2 and plasma 1,25-dihydroxyvitamin D were positively correlated both before (P less than 0.005) and after (P less than 0.005) hydrochlorothiazide, as was also the percentage change in each induced by the drug (P less than 0.05). Furthermore, the changes in plasma 25-hydroxyvitamin D and plasma 1,25-dihydroxyvitamin D after hydrochlorothiazide were negatively correlated (P less than 0.05). 4. It is suggested that a block of prostaglandin E2 synthesis plays a role in the effect of hydrochlorothiazide on Ca2+ metabolism, most probably through an inhibition of 1 alpha-hydroxylase activity.

Adult↗
PubMed1990

Glycosaminoglycan content, oxalate self-exchange and protein phosphorylation in erythrocytes of patients with 'idiopathic' calcium oxalate nephrolithiasis.

1. This study was performed to test the hypothesis that glycosaminoglycans may play an important role in the observed abnormalities in oxalate flux seen in patients with calcium oxalate nephrolithiasis. 2. Oxalate flux rate, erythrocyte membrane glycosaminoglycan content, membrane protein phosphorylation and effect of heparan sulphate on erythrocyte oxalate flux in vitro were studied in control subjects and patients with calcium oxalate nephrolithiasis. 3. In comparison with control subjects, renal stone-formers showed a significantly higher oxalate self-exchange, a lower erythrocyte membrane glycosaminoglycan content and a higher membrane phosphorylation rate. In stone-formers, erythrocyte glycosaminoglycan content correlated inversely with both oxalate flux rate and protein phosphorylation. In vitro, heparan sulphate promoted a significant fall in the rate of oxalate self-exchange. 4. These findings support the hypothesis that a lower erythrocyte membrane content of glycosaminoglycans enhances membrane protein phosphorylation, leading to an increased rate of transmembrane oxalate flux.

Adult↗
PubMed1987

Synthesis and calcium antagonistic activity of a new class of 1,4-dihydropyridines having an alkoxyimino group in position 3.

The synthesis of new 1,4-dihydropyridines having an alkoxyimino group in position 3 is described. Pharmacological evaluation included calcium antagonistic activity in the guinea pig Taenia coli test, acute toxicity and oral antihypertensive activity in SHR. The compounds had a remarkable calcium antagonistic activity in vitro and low toxicity, but no antihypertensive activity in vivo, probably due to an unfavourable pharmacokinetic profile.

Animals↗
PubMed1986

An inheritable anomaly of red-cell oxalate transport in "primary" calcium nephrolithiasis correctable with diuretics.

We measured the rate of oxalate flux across the red-cell membrane in the steady state in 114 patients with a history of calcium oxalate kidney stones and in 25 controls. Of the patients, 98 had recurrent, "idiopathic" kidney stones, 8 had primary hyperparathyroidism, 7 had renal or urinary tract malformations, and 1 had primary hyperoxaluria. Oxalate exchange was significantly higher in the 98 patients with idiopathic stone formation than in the controls (-1.10 +/- 0.95 [SD] X 10(-2) min-1 vs. -0.31 +/- 0.12 X 10(-2); P less than 0.001); it was above the upper limits of normal in 78 of these patients. All 8 patients with hyperparathyroidism and the patient with primary hyperoxaluria had values in the normal range; 2 of the patients with renal or urinary tract malformation had values at the upper normal limit. A study of five families indicated that the abnormality is an autosomal monogenic dominant trait with complete penetrance and variable expressivity. Oxalate-tolerance tests were carried out in five pairs of brothers. One brother in each pair had the abnormality in oxalate flux, and had a significantly higher percentage of oxalate excretion at two hours after oxalate loading (18.09 +/- 3.07 [SD] vs. 10.37 +/- 3.08 percent; t = 3.97; P less than 0.005) and four hours (14.87 +/- 2.91 vs. 9.89 +/- 2.93 percent; t = 2.70; P less than 0.05). Treatment with oral hydrochlorothiazide (50 mg per day) or amiloride (5 mg per day) or both restored normal or nearly normal red-cell oxalate exchange in all of 33 patients who initially had increased rates. We conclude that an inherited cellular defect in oxalate transport may be a factor in "primary" calcium oxalate stone formation and that this defect may be corrected with diuretics.

Adolescent↗