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Biomedical subjects

A Benigni

Publications and source records attributed to A Benigni.

At least 91 records · Page 5Linked to original sources
PubMed1991

In vitro platelet adhesion to dialysis membranes.

This work describes an in vitro system developed to quantitate platelet deposition on different dialysis membranes. The system is based on the use of small dialysis filters and reproduces the haemodynamic pattern of blood flowing through hollow fibres during in vivo dialysis. We have determined the in vitro platelet adhesion to cuprophan and to a non-cellulosic membrane, polymethylmethacrylate. When albumin concentration in the platelet suspension was low (0.35%) platelet deposition to cuprophan and to polymethylmethacrylate was comparable. When albumin concentration was increased to a physiological value (3.5%) platelet adhesion to both cuprophan and to polymethylmethacrylate membranes significantly decreased. This effect of albumin was greatest for the high-permeable polymethylmethacrylate membrane (BK). These data suggest that platelet membrane interaction is significantly influenced by circulating albumin.

Albumins↗
PubMed1990

Preliminary report: renal thromboxane A2 synthesis in children with frequent relapsing nephrotic syndrome.

An evaluation was made of the possible relation between renal thromboxane (Tx)A2 synthesis (measured as urinary excretion of TxB2) and the loss of glomerular permeability to proteins, in 5 children with seven episodes of minimal change nephrotic syndrome. Urinary TxB2 excretion was significantly higher in children with minimal change nephrotic syndrome than in 14 healthy controls, and reached its maximum at the time of peak proteinuria. During remission of nephrotic syndrome urinary excretion of TxB2 was still significantly higher than in healthy controls. A significant positive correlation between urinary excretion of TxB2 and proteinuria was observed in 3 patients. The results suggest that renal TxA2 could be regarded as one of the possible mediators of the altered glomerular permeability to proteins in minimal change nephrotic syndrome.

Child↗
PubMed1990

Role of enhanced glomerular synthesis of thromboxane A2 in progressive kidney disease.

Normotensive rats of the Milan strain (MNS) spontaneously develop focal glomerulosclerosis. In order to explore the contribution of glomerular thromboxane (TX) A2 synthesis to the development of the disease, we have characterized the time course of renal functional and biochemical changes, and their modification by long-term treatment with a TX-synthase inhibitor. Oral administration (150 mg.kg-1 from 1 to 14 months of age) of FCE 22178 suppressed enhanced glomerular TXB2 production at all experimental times (mean inhibition 80%) and proteinuria (varying between 27.1 and 73.0%) while preserving renal blood flow and glomerular filtration rate. These effects of TX-synthase inhibition were seen in the absence of any statistically significant changes in systemic blood pressure. Moreover, FCE 22178 had no antihypertensive effects in hypertensive rats of the Milan strain (MHS) nor in spontaneously hypertensive rats (SHR). Treatment also prevented the age-related hypoalbuminemia and hyperlipidemia observed in control MNS and significantly (P less than 0.01) reduced glomerular histologic damage, as demonstrated by light microscopy studies and measurement of sclerotic area. We conclude that: 1) MNS rats provide an animal model of long-lasting proteinuria characterized by an age-related increase in glomerular TXB2 production paralleled by progressive loss of renal structural integrity and function and by a secondary dyslipidemia; 2) pharmacological inhibition of glomerular TX-synthase attenuates the structural as well as the functional expression of kidney disease, without a primary effect on systemic blood pressure. These data are suggestive of an important modulating role of TXA2 in the progression of MNS renal disease.

Animals↗
PubMed1990

Endothelin and eicosanoid synthesis in cultured mesangial cells.

We investigated the effect of endothelin on the generation of eicosanoids, which are known to regulate basal and stimulated mesangial cell tone. The results showed that endothelin is a potent stimulus of prostaglandin E2 (PGE2), prostacyclin (PGI2), and thromboxane A2 (TxA2) synthesis by bovine mesangial cells. Percentage increases in eicosanoid synthesis induced by endothelin (10(-10) to 10(-6) M), were 50 to 275% for PGE2, 28 to 168% for PGI2 and 42 to 111% for TxA2, respectively. Endothelin-induced eicosanoid synthesis in mesangial cells was concentration, but not time dependent. Aspirin (500 microM) completely prevented endothelin-induced eicosanoid synthesis. The calcium entry blocker nitrendipine (10(-8) M) failed to inhibit endothelin-induced eicosanoid synthesis. These data suggest that endothelin-induced changes in renal circulation and glomerular function in normal and disease conditions may be modulated by the concomitant stimulation of mesangial eicosanoid synthesis.

Animals↗
PubMed1990

Functional implications of decreased renal cortical atrial natriuretic peptide binding in experimental diabetes.

Glomerular hyperfiltration in streptozotocin-induced diabetes mellitus in rats may be mediated by atrial natriuretic peptide (ANP). We wanted to evaluate plasma levels of ANP and plasma volume in relation to renal ANP receptor density and affinity in rats 6 weeks after induction of diabetes. Plasma levels of immunoreactive ANP were significantly higher in hyperglycemic diabetic (75.2 +/- 8.3 pg/ml) than in control animals (34.7 +/- 8.1 pg/ml; p less than 0.01). Administration of insulin to keep diabetic rats normoglycemic normalized plasma levels of immunoreactive ANP (30.5 +/- 5.2 pg/ml). In contrast, plasma volume did not show significant differences among the groups (hyperglycemic diabetes, 46.6 +/- 3.8; normoglycemic diabetes, 42.4 +/- 3.2; controls, 43.2 +/- 2.0 ml/kg body wt). No correlation was found between plasma levels of immunoreactive ANP and plasma volume. By autoradiography a significant reduction in the number of renal cortical ANP receptors was observed in hyperglycemic diabetic rats as compared with controls. At variance, ANP receptor affinity did not change either in the cortex or in the medulla in hyperglycemic diabetics in comparison with control animals. The pathophysiological implication of cortical ANP receptor down-regulation was underscored by the blunted response of glomerular filtration rate to ANP infusion in diabetic animals as compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Thromboxane synthesis inhibition increases renal prostacyclin and prevents renal disease progression in rats with remnant kidney.

Previous studies have demonstrated that inhibition of thromboxane A2-dependent platelet aggregation by the thromboxane A2 synthase inhibitor, OKY 1581, ameliorated the progressive kidney disease of rats with subtotal renal ablation. OKY 1581 also decreased the excessive renal thromboxane A2 synthesis and lowered systemic blood pressure. In the same model, a low dose aspirin and a specific thromboxane A2 receptor antagonist failed to influence proteinuria, glomerulosclerosis, and hypertension, thus excluding a role for either platelet or renal thromboxane A2 in renal disease progression. The aims of this study were to establish (1) whether a thromboxane A2 synthase inhibitor different from OKY 1581 could retard the progression of glomerular disease in rats with remnant kidney and (2) whether this effect was associated with an increase in renal synthesis of the vasodilatory prostacyclin. Treatment of rats with renal mass ablation with FCE 22178 (100 mg/kg by gavage and 200 mg/kg in the drinking water) for 35 days starting 10 days after surgical ablation was associated with an improvement in renal function in comparison with rats receiving the vehicle alone. Proteinuria was significantly lower, and rats were partially protected from the development of glomerulosclerosis. Systolic blood pressure was significantly lower than in animals given the vehicle. Urinary thromboxane B2 excretion was significantly decreased, and urinary 6-keto-prostaglandin F1 alpha increased in respect to vehicle-treated rats. We conclude that FCE 22178 limits glomerular injury in rats with remnant kidney.

6-Ketoprostaglandin F1 alpha↗
PubMed1990

[A comparative assessment of the capacity of 2 bleeding indices to represent the concentration of thromboxane B2 in the periodontal tissues].

Comparative assessment on the capability of two bleeding indexes to measure the concentration of thromboxane B2 in periodontal tissues. The aim of the study was to compare two bleeding indexes, the Gingival Bleeding Index (GBI) and the Gingival Bleeding Time Index (BTI) in evaluating the intensity of inflammation in deep periodontal tissues measured by the level of thromboxane B2 in the tissues themselves. Results showed that both bleeding indexes were closely correlated to tissue inflammation but that of the two, BTI is more significantly correlated. On the basis of these findings, the authors hope to see the application of bleeding indexes in clinical and research studies which can offer a graduated assessment of bleeding, thus increasing the specificity of this important diagnostic sign.

Adult↗
PubMed1989

Metabolism of thromboxane B2 in the isolated perfused rat kidney: mass spectrometric identification of urinary products.

The metabolism of thromboxane B2 (TXB2), the stable breakdown product of thromboxane A2, has been studied in isolated perfused kidney preparations using a recirculating system. In a first experiment, TXB2 was infused at a rate of 20 micrograms/kg per min. In a second experiment, a 1:1 mixture of TXB2 and octadeuterated TXB2 (0.4 microgram/kg per min each) was infused. Urinary samples collected during the infusion of TXB2 or vehicle were extracted on C18 cartridges and derivatized to methyl or pentafluorobenzyl ester, methyloxime, trimethylsilyl ether. Samples were analyzed by high-resolution gas chromatography-mass spectrometry in the electron impact and negative ion chemical ionization modes. Products of beta-oxidation, reduction of the delta 5,6 double bond and dehydrogenation at C-11 (2,3-dinor-TXB2, 2,3-dinor-TXB1, 2,3,4,5-tetranor-TXB1 and 11-dehydro-TXB2) were identified in addition to unmetabolized TXB2. 2,3,4,5-tetranor-TXB1 and 2,3-dinor-TXB1 were the most abundant metabolites.

Animals↗
PubMed1989

Quantitative profiling of 6-ketoprostaglandin F1 alpha, 2,3-dinor-6-ketoprostaglandin F1 alpha, thromboxane B2 and 2,3-dinor-thromboxane B2 in human and rat urine by immunoaffinity extraction with gas chromatography-mass spectrometry.

A rapid and simple method based on immunoaffinity extraction, stable isotope dilution and gas chromatography-mass spectrometry has been developed for profiling urinary metabolites of prostacyclin and thromboxane. 6-Ketoprostaglandin F1 alpha (6-keto-PGF1 alpha), 2,3-dinor-6-ketoprostaglandin F1 alpha (2,3-dinor-6-keto-PGF1 alpha), thromboxane B2 (TXB2) and 2,3-dinor-thromboxane B2 (2,3-dinor-TXB2) were quantitatively extracted from human or rat urine spiked with deuterated internal standards using mixed-bed columns containing immobilized anti-6-keto-PGF1 alpha and anti-TXB2 antibodies (cross-reacting with 2,3-dinor-6-keto-PGF1 alpha and 2,3-dinor-TXB2, respectively). The extract was directly derivatized to form pentafluorobenzyl ester, methyloxime, trimethylsilyl ether derivatives. Quantitation was performed by stable isotope dilution assay and high-resolution gas chromatography-negative ion chemical ionization mass spectrometry, by monitoring the carboxylate anions (M-181) of the derivatized metabolites. The method was applied to evaluate the urinary excretion of 6-keto PGF1 alpha, 2,3-dinor-6-keto-PGF1 alpha, TXB2 and 2,3-dinor-TXB2 in humans and rats. Results were in accordance with previously reported data obtained by other methods. Novel data on the urinary excretion of 2,3-dinor-6-keto-PGF1 alpha in rats under basal conditions are presented. This sensitive and selective method represents a significant advance in terms of rapidity and simplicity over other immunoaffinity-gas chromatography-mass spectrometry methods for measuring single prostanoids, such as 6-keto-PGF1 alpha or TXB2, since it allows profiling of a group of metabolites whose balance is important in several physiopathological conditions.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Effect of low-dose aspirin on fetal and maternal generation of thromboxane by platelets in women at risk for pregnancy-induced hypertension.

There is evidence that aspirin in low doses favorably influences the course of pregnancy-induced hypertension, but the mechanism, although assumed to involve suppression of the production of thromboxane by platelets, has not been established. We performed a randomized study of the effect of the long-term daily administration of 60 mg of aspirin (n = 17) or placebo (n = 16) on platelet thromboxane A2 and vascular prostacyclin in women at risk for pregnancy-induced hypertension. Low doses of aspirin were associated with a longer pregnancy and increased weight of newborns. Serum levels of thromboxane B2, a stable product of thromboxane A2, were almost completely (greater than 90 percent) inhibited by low doses of aspirin. The urinary excretion of immunoreactive thromboxane B2 was significantly reduced without changes in the level of 6-keto-prostaglandin F1 alpha, a product of prostacyclin. Mass spectrometric analysis showed that aspirin reduced the excretion of the 2,3-dinor-thromboxane B2 metabolite--mainly of platelet origin--by 81 percent and of thromboxane B2, probably chiefly of renal origin, by 59 percent. The urinary excretion of 6-keto-prostaglandin F1 alpha and of its metabolite 2,3-dinor-6-keto-prostaglandin F1 alpha was not affected. Low doses of aspirin only partially (63 percent) reduced neonatal serum thromboxane B2. No hemorrhagic complications were observed in the newborns. Thus, in women at risk for pregnancy-induced hypertension, low doses of aspirin selectively suppressed maternal platelet thromboxane B2 while sparing vascular prostacyclin, but only partially suppressed neonatal platelet thromboxane B2, allowing hemostatic competence in the fetus and newborn.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Blunted excretory response to atrial natriuretic peptide in experimental nephrosis.

Adriamycin (ADR) nephrosis and a model of unilateral ADR-induced proteinuria were produced in Sprague-Dawley (S.D.) rats to investigate the mechanism of sodium retention by the nephrotic kidney. Plasma volume, as measured by the dilution principle using radioiodinated serum albumin, was significantly higher in nephrotic animals than in control ones (NS: 69.61 +/- 15.02: control: 47.05 +/- 5.32 ml/kg: P less than 0.01). Similarly plasma levels of immunoreactive ANP (iANP) were significantly higher in nephrotic animals compared to controls (NS 104.22 +/- 36.41: control 59.94 +/- 20.88 pg/ml; P less than 0.05). Using the unilateral model we found a markedly reduced diuretic and natriuretic response to the infusion of synthetic rat atrial natriuretic peptide (ANP 1-28) in proteinuric kidney but not in contralateral kidney, despite a comparable increase in glomerular filtration rate. To explain the blunted diuresis and natriuresis in the presence of normal glomerular response to ANP, we investigated the possibility of an abnormality at post-glomerular level by studying ANP receptor density and affinity of the inner stripe of outer medulla and the inner medulla in ADR-and vehicle-treated rats. The inner stripe of outer medulla and the inner medulla receptor density and affinity were not significantly different in ADR rats as compared to animals given the vehicle alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Glomerular hyperfiltration and urinary prostaglandins in type 1 diabetes mellitus.

In order to determine whether glomerular hyperfiltration in diabetes is related to renal prostaglandin production we have studied the urinary excretion of PGE2, 6-keto-PGF1 alpha, and TXB2 in two sex, age and duration of diabetes matched groups of 9 and 10 Type 1 diabetic patients with either normal (mean 121, range 105-129 ml min-1 1.73 m-2) or supranormal glomerular filtration rate (154, 135-206 ml min-1 1.73 m-2). A group of 15 matched healthy volunteers served as control subjects. Urine was collected overnight for an uninterrupted period of at least 6 h. All studies in the patients were performed during insulin-induced sustained euglycaemia to prevent the confounding effect of variable degrees of blood glucose control on urinary prostaglandin excretion. Blood pressure was normal in all subjects. Urinary excretion of 6-keto-PGF1 alpha was significantly higher in the patients with glomerular hyperfiltration (median 17.1, range 4.5-33.6 ng h-1) than in those without (8.8, 1.5-13.8 ng h-1; p less than 0.05) or in normal control subjects (9.6, 5.2-15.5 ng h-1; p less than 0.05). No significant differences were found in the excretion rates of PGE2 and TXB2 between the three groups. Under conditions of controlled plasma glucose and insulin concentrations the urinary excretion of 6-keto-PGF1 alpha, the stable breakdown product of PGI2, a compound of endothelial, possibly glomerular, origin was elevated only in the diabetic patients with glomerular hyperfiltration.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Renal metabolism and urinary excretion of thromboxane B2 in the rat.

We wanted to evaluate whether the kidney tissue can metabolize thromboxane (Tx) B2 and, specifically, whether the 2,3-dinor metabolite might be formed in the kidney and excreted in the urine. For this purpose, we used an isolated perfused kidney preparation exposed to vehicle or TxB2 at different infusion rates. Approximately 96% of the total TxB2 infused was recovered in the venous effluent, whereas approximately 1% was found in urine. Isolated perfused kidneys exposed to [3H]TxB2 eliminated in the urine 1.2% of the [3H]TxB2 infused, measured by thin-layer chromatographic analysis, and actively metabolized [3H]TxB2 to 2,3-dinor-TxB2, 11-dehydro-TxB2, and possibly 2,3,4,5-tetranor-TxB1. No metabolites of TxB2 were recovered in the venous effluent. As a marker of renal TxB2 metabolic activity, urinary 2,3-dinor-TxB2 was quantified by high-resolution gas chromatography-negative-ion chemical ionization mass spectrometry. The 2,3-dinor-TxB2 was detected both before and during TxB2 infusion in urinary samples but not in the venous effluent. The ratio of 2,3-dinor-TxB2-TxB2 increased during the infusion reaching a peak value immediately after stopping the TxB2 infusion. These results indicate that, in the rat, the kidney tissue metabolizes TxB2 to 2,3-dinor-TxB2, and both TxB2 and 2,3-dinor-TxB2 are excreted in the urine.

Animals↗