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Biomedical subjects

A Vercellone

Publications and source records attributed to A Vercellone.

At least 73 records · Page 4Linked to original sources

Platelet cationic proteins are present in glomeruli of lupus nephritis patients.

Synthetic polycations have been shown to bind and neutralize glomerular polyanions (GPA), thereby increasing the permeability of the glomerular capillary wall (GCW). In the present study it is demonstrated that human platelet-derived cationic proteins (HuPlt CP), which are able to increase cutaneous vascular permeability, bind in vitro to the GCW following incubation of normal human kidney sections with purified HuPlt CP or with washed human platelets stimulated with thrombin, immune complexes (IC) and platelet-activating factor (PAF), or stimulated with a suspension of washed human platelets and polymorphonuclear leukocytes in the presence of phagocytable substrate. The antiserum used in immunofluorescence test to detect the binding of HuPlt CP was specific for two different molecular types of HuPlt CP, both with an isoelectric point (pI) of 10.5. Glomerular deposits of HuPlt CP were also detectable by immunofluorescence microscopy in renal glomeruli present in tissue obtained by biopsy from patients with systemic lupus erythematosus (SLE), a disease in which platelets have been implicated as mediator of glomerular injury. These data indicate that when activated platelets release HuPlt CP in vivo, these proteins bind to glomerular structures. The binding of HuPlt CP to GCW appears to be ionic in nature since heparin, a polyanion, prevents this binding in vitro. In addition, heparin, as well as a high molarity buffer, removed deposits of HuPlt CP bound in vitro to normal GCW or bound in vivo to glomeruli of patients with SLE. The binding of HuPlt CP to GCW is associated with loss of colloidal iron staining, a qualitative technique that demonstrates primarily epithelial cell surface anionic sialoglycoproteins. In experiments of in vitro binding of purified HuPlt CP to section of normal kidney treatment with heparin completely restores the normal pattern of colloidal iron staining suggesting ionic neutralization of GPA. In contrast, heparin is only partially effective in restoring colloidal iron staining in normal kidney sections treated with platelets directly stimulated with IC or PAF or in kidney sections of patients with SLE. These observations indicate that under these conditions the ionic interaction of HuPlt CP with GCW is only partially responsible for the loss of colloidal iron staining. The results of the present study suggest that biologically active polycationic mediators released from stimulated platelets localize in GCW and participate in the induction of glomerular injury.

Adult↗

Echo-Doppler velocimetry in the diagnosis of renal artery stenosis on transplanted kidney.

Renal artery stenosis is one of the most important complications in the natural history of kidney transplantation. Particular care has to be taken in the use of angiography techniques because of the invasiveness and of the potential toxicity of radiopaque contrast material, even in the less invasive radiological tests, like endovenous sequential angiourography with image subtraction (SAU) and digital subtraction angiography (DSA). Fifty-one patients have been examined with echo-Doppler velocimetry (EDV) and also with SAU in order to verify the previous status of the artery. EDV exhibits a 100% sensitivity: all SAU detected stenosis have been formerly identified via EDV. The non-invasiveness and possibility of early repetition allows an early diagnosis capability for all transplanted patients. In this way, a surgical intervention may quite often be prevented by a precocious use of endoluminal angioplasty.

Adult↗

Clinical and therapeutic correlations in consumption coagulopathy of obstetric acute renal failure.

Heparin has been proposed following the supposed role of disseminated intravascular coagulation (DIC) in the pathologies associated with the consumption coagulopathies such as obstetric acute renal failure (ARF), whilst antifibrinolytic agents could be advocated to stop a simultaneous triggered fibrinolysis. Out of 26 obstetric ARF DIC may be demonstrated in 10 and supposed in 6 patients who developed severe post-partum uterine bleeding. Therapeutic schedules employing heparin or antifibrinolytic agents early post-partum do not seem to change either the behaviour of laboratory parameters (showing a DIC partial resolution within 48 hours), or heavy bleeding in respect to the patients treated with supportive therapies alone. Furthermore, heparin administered during the following days does not seem to be a crucial factor in the renal recovery, and is often followed by severe haemorrhagic complications. Fresh frozen plasma after aprotinin is able to stop bleeding in the presence of persisting signs of consumption without damaging renal recovery.

Acute Kidney Injury↗

Heparin transfer across the rabbit peritoneal membrane.

Variable quantities of heparin have been proposed to avoid intraperitoneal clotting during peritoneal dialysis without the risk of systemic effects, because heparin is presumed to be incapable of passing through the peritoneal membrane. This study set out to verify this assumption by using labeled heparin in experimental dialysis in 7 New Zealand white rabbits. Heparin was labeled with 99mTc. Labeling quality, assessed by two chromatographic checks, showed less than 5% of free pertechnetate. Chromatographic determinations showed more than 95 and 80% of labeled heparin in inflow and outflow dialysates and in blood samples respectively. Following sodium thiopental anesthesia, animals underwent three protocols: a single 15 min cycle of time diffusion with heparin 500 U/l (A), 6 successive 15 min cycles with heparin 500 U/l (B), and a single 3 h cycle with heparin 2,500 U/l (C). Labeled heparin was found in blood organs and urine in variable percentages. The total amount of recovered radioactivity ranged from 1.5% (A) to 20% (C) of that introduced. It may be concluded that heparin passes through the peritoneum according to some law dependent on the amount used and the diffusion time.

Animals↗

Hypervitaminosis B12 in maintenance hemodialysis patients receiving massive supplementation of vitamin B12.

We have administered routinely a multivitamin preparation containing a megadose of B12 to 106 hemodialysis patients after dialysis treatments. We found that these patients had very high levels of serum vitamin B12 which returned to original values only after a period of three years after stopping the vitamin. Discontinuing therapy had no effect on hemoglobin, mean erythrocyte corpuscular volume, or motor nerve conduction velocity. It is not known whether maintaining a prolonged high level of vitamin B12 is harmful. However, animal and epidemiologic studies have suggested that both cobalamin and cobalt may be potentially toxic. In view of the absence of demonstrable benefit and the possible risk of toxicity, we believe that the use of such megadose vitamin compounds in dialysis patients should be re-evaluated.

Adult↗

In vivo localization of C3 on the brush border of proximal tubules of kidneys from nephrotic patients.

Deposits of C3 but not of C1q and C4 were detected on the proximal tubules of kidneys from nephrotic patients with non-selective proteinuria. The incidence of tubular C3 deposits was significantly higher in patients with membranous glomerulonephritis, focal glomerulosclerosis, membrano-proliferative glomerulonephritis and non-selective proteinuria than in patients with minimal change disease, nephrotic syndrome and selective proteinuria or in patients with glomerular disease, but without nephrotic syndrome. The occurrence of tubular C3 deposits was positively correlated with the amount of urinary C3 excretion. In vitro studies showed that the human normal kidney as well as pathologic specimens negative for in vivo tubular C3 deposits were able to bind C3 on the brush border of proximal tubules when incubated with fresh heterologous serum. In contrast, in patients with non-selective proteinuria and in vivo tubular C3 deposits, the binding of heterologous C3 to the brush border of proximal tubules was markedly reduced. The positive correlation between the occurrence of tubular C3 deposits and the urinary complement excretion, together with the detection of the C3 breakdown products in the urines further supported the hypothesis that complement components, once filtrated through the glomerular barrier, might be activated by the brush border of the proximal tubule.

Adolescent↗

Direct interaction between polymorphonuclear neutrophils and cuprophan membranes in a plasma-free model of dialysis.

Plasma-free, purified, normal, human polymorphonuclear neutrophils (PMN) were recirculated for 60 minutes in an experimental model of dialysis using cuprophan membranes and acetate or bicarbonate dialysate. At different time intervals, the intracellular contents of PMN-derived cationic proteins (NCP), the release of lysosyme, beta-glucuronidase and PAF as well as the occurrence of PMN and platelet aggregating activities in the supernatants were evaluated. The formation of PMN aggregates, the depletion of intracellular contents of NCP together with the release of lysosomal constituents occurred early (5-10 min) in the course of recirculation. These events were concomitant with the occurrence of PMN aggregating activity in the supernatants due to the release of NCP, as it was antagonised (30-40%) by a rabbit anti-human NCP, and to the release of PAF which also accounted for the platelet aggregating activity that was independent from both adenosine diphosphate and cyclo-oxygenase inhibitors. These data suggest that direct interaction occurs between human PMN and cuprophan in in vitro conditions in the absence of plasma factors and point to a role for cellular mediators in the pathogenesis of the intravascular alterations occurring early in haemodialysis.

Cell Aggregation↗

Muzolimine in chronic renal failure: a study in 16 patients.

Muzolimine is a diuretic with chemical features different from all other known diuretics, and its use seem to be particularly interesting in patients with chronic renal failure. In fact, similarly to furosemide, muzolimine presents a strong action on Henle's loop but with a slower and more lasting effect, as experimentally demonstrated in both animals and man. We used high doses muzolimine (240, 480, 720 mg/die) in 16 patients with chronic renal failure (creatinine clearance less than 20 ml/min) and clinical pattern of important hydrosaline retention (6 primitive glomerulonephritis, 3 interstitial nephrites, 1 vascular nephropathy, 1 diabetic nephropathy, 1 lupus nephritis, 1 amyloidosis, 1 polycystic nephropathy and 2 nephropathies of unknown diagnosis). Muzolimine diuretic action was compared with furosemide 500 mg/die. The schedule employed was: furosemide 500 mg/die for 5 days followed by 6 days of muzolimine treatment at increasing doses (240 mg on 1st and 2nd day, 480 mg on 3rd and 4th, 720 mg on 5th and 6th). In all patients (undergoing a diet constant in water, sodium, potassium and protein content) body weight, blood pressure, heart rate, serum and urinary electrolyte concentration, serum and urinary uric acid, BUN, creatinine clearance, glycaemia, hematocrit and hemoglobin were daily controlled. A clinical and laboratory investigation of the possible side effects was also assessed; in particular liver enzymes, bilirubin and total serum proteins were considered. In our study muzolimine increased the renal excretion of water, sodium and chloride in all cases. This effect is more evident during the treatment with the highest dose (720 mg/die) but already appears with the 480 mg/die dose and is higher than that obtained with comparable doses of furosemide.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Platelet-activating factor-induced loss of glomerular anionic charges.

The urinary protein excretion rate, the glomerular localization of cationic proteins (CP) derived from platelets and polymorphonuclear neutrophils (PMN) and the loss of fixed anionic charges were studied in rabbits infused with synthetic 1-0-octadecyl-2-acetyl-sn-glyceryl-3-phosphorylcholine [platelet activating factor (PAF), 1.5 micrograms/kg in 2 ml of saline containing 0.25% bovine serum albumin (BSA)]. The urinary protein excretion rate, unaffected by diphenhydramine, an antihistaminic agent, reached its maximum at 180 min and decreased 24 hr after PAF infusion. The localization of CP derived from platelets and PMN was investigated by immunofluorescence using specific antisera. Platelet-derived CP were detectable in glomeruli at 15 min and, particularly, at 180 min after PAF infusion. Cells positive for CP derived from PMN accumulated within 15 min in the glomerular capillaries and, later (180 min), cytoplasmic depletion and localization in glomerular capillary walls occurred. CP deposits were associated with the loss of fixed anionic charges as detected by ruthenium red and colloidal iron staining. Rabbits infused with 1-0-octadecyl-sn-glyceryl-3-phosphorylcholine (lyso-PAF) or saline-BSA alone had none of the alterations described above. The development of proteinuria, the glomerular localization of platelet- and PMN-derived CP and the concomitant loss of fixed anionic charges suggested the possibility that, once CP were released in the circulation from PAF-stimulated platelets and PMN, they bound to, and neutralized, fixed anionic charges, resulting in enhanced glomerular permeability.

Animals↗

Urokinase treatment for arteriovenous fistulae declotting in dialyzed patients.

Urokinase treatment, previously employed with success in the declotting of deep venous thrombosis and arteriovenous shunts in patients undergoing regular dialytic treatment (RDT), was used in 23 cases of arteriovenous fistula thrombotic occlusion in 18 RDT patients. The treatment was successful in 65.2% of the cases without any negative side effects, except 1 case which may have developed a pulmonary embolism. Patients with severe hypofibrinolysis may need larger doses or may have a recurrence of the thrombotic episode. All therapeutic failures correlated with the presence of fibrosis or sclerosis.

Adult↗