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Biomedical subjects

G Remuzzi

Publications and source records attributed to G Remuzzi.

At least 451 records · Page 25Linked to original sources
PubMed1984

The metabolism of arachidonic acid by platelets in nephrotic syndrome.

The production of malondialdehyde (MDA) and thromboxane B2 (TxB2) by platelets following an arachidonic acid (AA) challenge was greater in nephrotic platelet rich plasma (PRP) than in normal PRP. The uptake of 14C-AA, and its subsequent conversion to 14C-TxB2 following a thrombin stimulus, was also greater in nephrotic than normal PRP. Normal plasma diminished the MDA production by nephrotic platelets. The addition of albumin to nephrotic PRP, or, the intravenous infusion of albumin in quantities sufficient to correct hypoalbuminemia also diminished the excessive production of prostaglandin metabolites by nephrotic platelets. The platelet aggregate ratio (PAR), which measures circulating platelet aggregates, was abnormal during the acute phase of nephrotic syndrome but reverted to normal following remission. These data indicate that hypoalbuminemia is associated with increased AA metabolism by platelets and suggest that platelet "hyperactivity" may contribute to the proclivity toward thrombosis observed in nephrotic syndrome.

Albumins↗
PubMed1984

Stimulation of prostacyclin synthesis in vascular cells by mononuclear cell products.

Supernatants were obtained from human peripheral blood mononuclear cells stimulated with phytohemagglutinin or in a mixed lymphocyte reaction. The effect of mononuclear cell products on vascular prostacyclin (PGI2) production was measured using cultured rat aortic smooth muscle cells (SMC) or aortic rings. PGI2 was measured by radioimmunoassay of its metabolite, 6-keto-PGF1 alpha. Supernatants containing mononuclear cell products induced PGI2 production in vascular tissue. Supernatant-induced PGI2 production of SMC was relatively slow, requiring more than six hours of incubation with supernatants, and was completely prevented by aspirin, a cyclooxygenase inhibitor. The regulation of arachidonic acid metabolism by products of stimulated mononuclear cells, which is critical to the physiology and pathology of blood vessels, may be an important aspect of the interaction between immunocompetent cells and vascular tissue.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Heparin for hemodialysis: practical guidelines for administration and monitoring.

Anticoagulation of extracorporeal circuit still represents a major problem for hemodialysis units. Uraemic patients are at risk of hemorrhages, so anticoagulant could increase such a risk. On the other hand clotting of extracorporeal circuit may complicate inadequate heparin administration or hemostatic activation by the foreign surfaces. In this article we propose a simple standard for heparin administration and monitoring which allows the theoretical best anticoagulation for extracorporeal circuit. Our data also indicate that the effect of our proposed schedule is not influenced by the type of membrane or dialyser used.

Adult↗
PubMed1984

Steroids and Adriamycin nephrosis.

Adriamycin induces a nephrotic syndrome in rats characterized by severe ultrastructural changes of visceral epithelial cells similar to those observed in puromycin aminonucleoside (PA) nephrosis and in human 'minimal changes' glomerulopathy. Since steroids have been shown to be effective in human 'minimal changes' glomerulopathy and in PA nephrosis, we undertook the present study to assess whether steroids had a therapeutic effect on adriamycin nephrosis. Groups of rats injected with different doses of adriamycin were subsequently treated with prednisolone. No significant differences were observed in proteinuria and in ultrastructural findings between the control and the steroid-injected animals. This study suggests that the mechanism underlying adriamycin-induced nephrotic syndrome might be different from that responsible for PA nephrosis or human 'minimal changes' glomerulopathy.

Animals↗
PubMed1983

Effect of Cyclosporin A on prostacyclin synthesis by vascular tissue.

NZW rabbits with acute serum sickness given Cyclosporin A (CyA) 25 mg/kg/day develop glomerular capillary thrombosis similar to that seem in the haemolytic uraemic syndrome (HUS). Bone marrow recipients treated with CyA may also develop a similar renal lesion associated with a haemolytic uraemic-like syndrome. In the HUS, impaired production of prostacyclin by vascular tissue may be found and has been associated with a lack of a plasma factor which stimulates prostacyclin synthesis. We therefore examined, in six normal rabbits, treated with CyA 25 mg/kg for five days, the ability of plasma from treated and untreated rabbits to stimulate prostacyclin synthesis from normal rabbit aortic rings. Plasma from untreated rabbits produced 21.5 +/- 6.9 ng 6-keto PGF1 alpha/ml/mg wet weight aorta (mean +/- SEM). However, the ability of plasma from CyA-treated rabbits to stimulate prostacyclin production was profoundly reduced. This was apparent within 24 hours of starting and persisted for seven days after therapy was stopped: mean of values from all rabbits bled from start of therapy until seven days after therapy stopped was 3.7 +/- 0.5 ng/ml/mg. We suggest that the renal complications of CyA therapy are related to a failure of normal vascular prostacyclin synthesis due to lack of a prostacyclin-stimulating plasma factor.

Animals↗
PubMed1983

Deamino-8-D-arginine vasopressin shortens the bleeding time in uremia.

In a randomized double-blind cross-over trial we gave either 1-deamino-8-D-arginine vasopressin or placebo to 12 patients with uremia, hemorrhagic tendencies, and prolonged bleeding times. After vasopressin infusion, all patients had shortened bleeding times, with the effect lasting for at least four hours in most cases. Platelet count, platelet cyclic AMP levels, platelet retention on glass beads, plasma fibronectin, serum thromboxane B2 and residual prothrombin, hematocrit, and plasma osmolarity were unchanged after vasopressin. A consistent post-infusion increase in factor VIII coagulant activity and, to a lesser extent, in factor VIII-related antigen and ristocetin cofactor accompanied the shortening of bleeding time. In addition, vasopressin induced the appearance in plasma of larger von Willebrand-factor multimers than those present in the resting state. The compound was given to nine additional patients with acute or chronic renal failure and prolonged bleeding times, before major surgery or renal biopsy. In these patients, shortening of the bleeding time was associated with normal hemostasis. Our findings indicate that 1-deamino-8-D-arginine vasopressin can be used for temporary correction of bleeding time and may prevent surgical bleeding in patients with uremia.

Adult↗
PubMed1983

In vivo platelet activation with in vitro hyperaggregability to arachidonic acid in renal allograft recipients.

Renal allograft recipients were investigated to determine the extent and possible nature of in vivo platelet activation. In 92 allografted patients stable for more than 4 months' duration, intraplatelet serotonin in circulating platelets was depleted significantly. In a further 16 patients studied serially for 12 to 16 weeks following transplantation, intraplatelet serotonin fell abruptly within 4 days from transplantation to very low levels, and remained thus for 10 weeks, rising toward normal at about 12 weeks. Although some patients showed abrupt falls in intraplatelet serotonin coincident with acute rejection episodes, there was no difference in intraplatelet serotonin in seven patients whose grafts functioned well immediately and remained stable, and seven in whom repeated rejection led to graft loss within 3 months. Thus, these tests of platelet function do not permit diagnosis of rejection or prediction of graft outcome. Plasma platelet factor 4 (PF4) concentrations, in contrast, were normal in most patients during the first 6 weeks after grafting, then rose and remained abnormal up to 13 years following the allograft in the long-term stable graft recipients. This discrepancy suggests a different mode of platelet activation in the first few weeks after grafting from subsequent months. Despite universal depletion of intraplatelet amines and alpha-granule contents only four out of 14 early allograft recipients had an abnormal bleeding time, and platelet aggregation thresholds with adenosine-5'-diphosphate and collagen were not different from controls. However, thresholds for platelet aggregation with arachidonic acid were reduced significantly (P less than 0.01) and thromboxane B2 generation was increased in vitro. There was no correlation between depletion of intraplatelet serotonin and circulating platelet-agglutinating material, but nine of 17 biopsy specimens from rejecting allografts taken during the first 3 months showed extensive glomerular localization of platelet membrane antigens and PF4.

Adenosine Diphosphate↗
PubMed1983

Reduced platelet thromboxane formation in uremia. Evidence for a functional cyclooxygenase defect.

A qualitative platelet abnormality and a bleeding tendency are frequently associated with renal failure and uremia. We demonstrated previously that uremic patients display an abnormal platelet aggregation to arachidonic acid and reduced malondialdehyde production in response to thrombin and arachidonic acid. The objectives of this investigation were: (a) to compare platelet prostaglandin (PG) and thromboxane (TX) production in whole blood and in platelet-rich plasma (PRP) of 21 uremic patients and 22 healthy subjects; (b) to evaluate the concentration and activity of platelet PG- and TX-forming enzymes; (c) to assess the functional responsiveness of the platelet TXA(2)/PGH(2) receptor; (d) to explore the hemostatic consequences of partially reduced TXA(2) production.Platelet immunoreactive TXB(2) production during whole blood clotting was significantly reduced, by approximately 60%, in uremic patients as compared to age- and sex-matched controls. Exogenous thrombin (5-30 IU/ml) failed to restore normal TXB(2) production in uremic platelets. Uremic PRP produced comparable or slightly higher amounts of TXB(2) than normal PRP at arachidonate concentrations 0.25-1 mM. However, when exposed to substrate concentrations >2 mM, uremic PRP produced significantly less TXB(2) than normal PRP. To discriminate between reduced arachidonic acid oxygenation and altered endoperoxide metabolism, the time course of immunoreactive TXB(2) and PGE(2) production was measured during whole blood clotting. The synthesis and release of both cyclooxygenase-derived products was slower and significantly reduced, at all time intervals considered. Furthermore, PGI(2) production in whole blood, as reflected by serum immunoreactive 6-keto-PGF(1alpha) concentrations, was significantly reduced in uremic patients as compared with healthy subjects. PGH synthase levels, as determined by an immunoradiometric assay, were not significantly different in platelets from uremic patients as compared to control platelets. A single 40-mg dose of aspirin given to five healthy volunteers reduced their serum TXB(2) to levels found in uremic patients. This was associated with a significant increase of threshold aggregating concentrations of ADP and arachidonic acid and prolongation of bleeding time. Substantially similar threshold concentrations of U46619, a TXA(2) agonist, induced aggregation of normal and uremic platelets. Prostacyclin induced a significant elevation of uremic platelet cyclic AMP, which was suppressed by U46619, further suggesting normal responsiveness of the TXA(2)/PGH(2) receptor. WE CONCLUDE THAT: (a) an abnormality of platelet arachidonic acid metabolism exists in uremia, leading to a reduced TXA(2) production; (b) the characteristics of this abnormality are consistent with a functional cyclooxygenase defect; (c) reduced TXA(2) production may partially explain the previously described abnormality of platelet function in uremia.

Adult↗
PubMed1983

Severe glomerular epithelial cell damage does not prevent passive Heyman nephritis in rats.

Passive Heymann nephritis (PHN) is an experimental model of membranous glomerulopathy in the rat ascribed to in situ formation of immune complexes. Very recently the demonstration that the aminonucleoside of puromycin provides some protection against PHN has highlighted the role of intrinsic properties of the glomerulus in immune complex formation. Adriamycin, a widely employed chemotherapeutic agent, is known to induce a nephrotic syndrome in rats characterized by severe ultrastructural changes of glomerular epithelial cells and by loss of glomerular polyanionic charges. We have studied the effect of pre-treatment with adriamycin on glomerular immune deposits in PHN using immunomorphological and quantitative techniques. In normal rats (group 1) injection of heterologous antibodies to proximal tubular brush border antigen (anti-FxIA), rapidly induces subepithelial immune deposits, as observed by immunofluorescence. Pre-treatment of rats with adriamycin (group 2) 48 hr before injection of anti-FxIA antibodies, when proteinuria is absent, does not alter the immunohistological findings of PHN. Heavily proteinuric rats (group 3) pre-treated with adriamycin 13 days before injection of anti-FxIA did not show any significant difference from groups 1 and 2. Species binding of injected anti-FxIA antibodies, studied by paired label techniques, was similar in normal rats and in proteinuric and non-proteinuric rats treated with adriamycin. The only difference was in the group of proteinuric rats treated with adriamycin, in which at 5 hr binding in the kidney was higher, due to tubular brush border binding as shown by immunofluorescence. This study indicates that local changes of the glomerulus and loss of glomerular histochemical properties do not invariably alter the glomerular deposition of immune complexes.

Animals↗
PubMed1982

Haemolytic uraemic syndrome: therapeutic effect of plasma infusion.

The therapeutic effect of plasma infusion was evaluated in 10 children and seven adults with haemolytic uraemic syndrome. All but one patient responded to this treatment with rapid disappearance of haematological abnormalities. The patient who apparently failed to respond to plasma infusion obtained complete remission of the disease after plasmapheresis. Although 15 of the 17 patients were anuric or oliguric on admission, renal function recovered completely in eight children and two adults. Seven patients showed residual chronic renal failure and two required long-term maintenance haemodialysis. Treatment with plasma was also successful in patients with relapses or recurrent episodes. Plasma infusion is a promising therapeutic approach for the haemolytic uraemic syndrome and deserves further study in clinical trials.

Adolescent↗
PubMed1982

Adriamycin-induced nephrotic syndrome in rats: sequence of pathologic events.

Adriamycin has been suspected of causing experimental nephrotoxicity. We report here that adriamycin induces a nephrotic syndrome in rats, proteinuria beginning 4 to 5 days after a single intravenous injection (7.5 mg. per kg. of body weight). The full expression of the syndrome develops 13 to 15 days later. Minimal alterations at light microscopy, negative immunofluorescence, and only some focal "fusion" of foot processes can be observed by electron microscopy in the early phase after injection (28 hours). At 13 days, loss of foot process architecture, and replacement by flattened epithelial cytoplasm, was invariably found. These ultrastructural findings became extensive at 28 days follow-up. Colloidal iron staining of kidney biopsies revealed loss of glomerular polyanions as early as 3 hours and very marked loss at 28 hours after adriamycin injection. Polyanions were totally absent at 13 days and were still undetectable at 28 days. Thus, the loss of polyanionic charges associated with the sialic acid coat precedes the ultrastructural changes and the onset of proteinuria. These changes appeared similar to those reported in rats treated with daunomycin or puromycin animonucleoside. The present study supports in a different animal model the concept that both morphologic changes and proteinuria are the consequence of a common primary event that is the loss of glomerular fixed negative charges.

Animals↗