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Biomedical subjects

F Perfumo

Publications and source records attributed to F Perfumo.

At least 91 records · Page 5Linked to original sources

Renal purine efflux and xanthine oxidase activity during experimental nephrosis in rats: difference between puromycin aminonucleoside and adriamycin nephrosis.

1. The hypothesis was tested that the renal xanthine oxidase system provides a source of oxygen free radicals in puromycin aminonucleoside and adriamycin experimental nephrosis by generating uric acid from hypoxanthine and xanthine. 2. The concentrations in renal tissue of the putative intermediary products of puromycin aminonucleoside metabolism, hypoxanthine and xanthine, and of their precursors, adenosine and inosine, were lower in rats treated with puromycin aminonucleoside than in normal controls, whereas concentrations of the metabolites were normal after adriamycin intoxication. Their daily urinary excretion was lower in the 24 h after puromycin aminonucleoside administration compared with the baseline values and returned to near normal levels within 5 days. After adriamycin the 24 h urinary excretion of xanthine and uric acid was double the baseline levels (P less than 0.001). 3. When equimolar amounts of hypoxanthine were injected instead of puromycin aminonucleoside, the concentration of all bases increased slightly in renal tissue and their urinary efflux was double the baseline level: allantoin, uric acid, the unmodified nucleotide and xanthine were the most represented compounds in urine. 4. The enzymatic activities relative to xanthine oxidase (EC 1.1.3.22) and xanthine dehydrogenase (EC 1.1.1.204) in renal tissues were unchanged 1 day after puromycin aminonucleoside or hypoxanthine intoxication and only moderately increased in both groups at 13 days (the time of appearance of heavy proteinuria in the puromycin aminonucleoside-treated group). In contrast, xanthine oxidase and xanthine dehydrogenase activities were higher in adriamycin-treated rats at 1 and 15 days after the treatment (P less than 0.001). 5. Feeding rats with normoprotein diets containing tungsten induced a marked and constant decrease of renal xanthine oxidase and xanthine dehydrogenase activities to 20% of the baseline values in both puromycin aminonucleoside- and adriamycin-treated rats. Inhibition of renal xanthine oxidase and xanthine dehydrogenase activities by tungsten was associated with a marked reduction (P less than 0.001) of proteinuria in adriamycin-treated rats and the same occurred with allopurinol, a specific inhibitor of xanthine oxidase activity. In contrast, tungsten treatment did not reduce the proteinuria associated with puromycin aminonucleoside, which reached a maximum 13 days after puromycin aminonucleoside intoxication. Hypoxanthine-treated rats were normoproteinuric after 2 months of observation. 6. These data demonstrate an activation of renal xanthine oxidase and xanthine dehydrogenase after adriamycin intoxication which is relevant to the induction of proteinuria. They also argue against the involvement of the renal xanthine oxidase system as a source of free radicals in puromycin aminonucleoside nephrosis and suggest that the nucleotide cycle is not a normal route for puromycin aminonucleoside degradation.(ABSTRACT TRUNCATED AT 400 WORDS)

Allantoin↗

Low-protein diet and xanthine-metabolising enzymes in adriamycin nephrosis.

Proteinuria and renal xanthine metabolising enzymes, xanthine oxidase and xanthine dehydrogenase, were evaluated in Adriamycin-treated rats fed standard (21% casein) and low-protein (6% casein) diets. In rats fed a standard diet Adriamycin was associated with increased activities in the kidney of xanthine oxidase and xanthine dehydrogenase and induced massive proteinuria. The pharmacological block of both enzymes by allopurinol and tungsten block of both enzymes by allopurinol and tungsten reduced proteinuria to one-third of the original levels. Rats fed a low-protein diet presented decreased levels of renal xanthine oxidase and xanthine dehydrogenase and were only slightly proteinuric. Finally, rats shifted from a low-protein diet to a normal one developed massive proteinuria in spite of normal or slightly decreased levels of renal xanthine oxidase and xanthine dehydrogenase. We conclude that a low-protein diet is effective in decreasing the levels of xanthine metabolising enzymes that are in part responsible for the renal damage due to Adriamycin. This is not however the unique mechanism by which the low-protein diet protects against the development of proteinuria in Adriamycin nephrosis; other factors must also be hypothesised.

Animals↗

Hypertension and renal selectivity properties in diabetic microalbuminuria.

The renal selectivity properties towards albumin were evaluated in ten diabetic patients with arterial hypertension before and after the pharmacological normalisation of blood pressure, and were compared to 12 subjects with essential hypertension. While all patients of the control group were normoalbuminuric during hypertension, six of the diabetic group were microalbuminuric when hypertensive and became almost normoalbuminuric after blood pressure pharmacological control. All microalbuminuric diabetic patients presented altered properties of renal selectivity as epitomised by a non-preferential urinary excretion of glycosyl albumin (GA) (urinary GA/serum GA less than or equal to 1). At variance the selectivity properties were normal in normoalbuminuric diabetic patients and in essential hypertension. It was concluded that in diabetes mellitus arterial hypertension is associated with microalbuminuria when the renal properties of selectivity are altered, but does not implicate any proteinuric effect in those cases where the GBM function is preserved.

Adult↗

Continuous ambulatory peritoneal dialysis (CAPD) of children with amino acid solutions: technical and metabolic aspects.

The changes in plasma and dialysate amino acids (AA) in 7 continuous ambulatory peritoneal dialysis (CAPD) children after dialysis with a 1% AA solution were compared with a glucose-containing solution. During the AA-exchange, the plasma levels of individual AA reached their peaks after 1 h, with their percentage increments significantly correlated (p less than 0.001) with the ratio of the amount of AA in the bag to the basal plasma concentration. The plasma concentration of methionine, valine, phenylalanine, and isoleucine remained higher than the basal value at 4 h. The amount of AA absorbed was 66% after 1 h, and 86% after 4 h and 6 h, corresponding to 2574 +/- 253 mumol/kg body wt. During glucose-dialysis (1.36%), levels of histidine, methionine, valine, phenylalanine, and isoleucine were significantly decreased in plasma after 1 h, and stayed low throughout the dialysis period. The loss of AA with the peritoneal effluent was 116 +/- 69 mumol/kg/body wt. From this study, it seems that using an AA dialysis solution, with 1 exchange per day, might limit the daily glucose load and compensate for AA losses by supplying an extra amount of AA and by reducing the loss of other AA not contained in dialysis solutions. The AA pattern in plasma following AA-dialysis resembles that observed after a protein meal, with no signs of persistently high, nonphysiological levels.

Adolescent↗

Autosomal dominant polycystic kidney disease: prenatal diagnosis by DNA analysis and sonography at 14 weeks.

A pregnant woman affected with autosomal dominant polycystic kidney disease (ADPKD) had a history of an affected fetus, diagnosed by sonography at 29 weeks of pregnancy. The proband's father was also affected. DNA analysis performed on chorionic villi at 11 weeks during a second pregnancy predicted an affected fetus, and sonographic examination at 14 weeks confirmed the diagnosis.

Adult↗

Peroxidative damage of the erythrocyte membrane in children with nephrotic syndrome.

The structural composition of erythrocyte ghosts was analysed in children affected by steroid-responsive (SRNS) and unresponsive nephrotic syndrome (SUNS). No variation of either intrinsic or extrinsic ghost proteins was found by discontinuous SDS-electrophoresis associated with a very sensitive double staining technique. By contrast, the composition of inner-layer phospholipids--phosphatidyl ethanolamine (PE) and phosphatidyl serine (PS)--was altered in SRNS with minor changes also involving phosphatidic acid, phosphatidyl inositol and lysophosphatidyl choline. Signs of peroxidative damage were present in both SRNS and SUNS ghosts and inside the cells; these included high levels of fluorescent amino-iminopropene derivates of PE and PS, increased intraerythrocytic amounts of malonyldialdehyde and decreased levels of reduced glutathione. Taken together these results support the concept that in SRNS and SUNS erythrocytes are target cells for peroxidative damage. In SRNS peroxidation of membrane lipids results in a marked alteration of the phospholipid composition of erythrocyte ghosts.

Adolescent↗

In vitro evidence for impaired cellular immune responsiveness in children with chronic renal failure.

We used mixed lymphocyte culture (MLC) as an assay to evaluate in vitro the cellular immune functions of children with chronic renal insufficiency (CRI) or with chronic renal failure (CRF). The proliferative response of lymphocytes from both groups of patients was significantly reduced as compared to the response of control individuals. In addition, the proliferative response of CRF patients treated with hemodialysis was significantly lower than the response of continuous ambulatorial peritoneal dialysis (CAPD) patients. These data confirm that a marked depression of the cellular immune response is detectable in a pediatric population, as predicted from data from the literature on the adult renal failure population.

Child↗

Endogenous albumin as a marker of renal selectivity in steroid-unresponsive nephrotic syndrome.

Albumin electrical charge, conformation and hydrophobicity taken as indexes of renal selectivity were evaluated in 8 children affected by steroid-unresponsive nephrotic syndrome associated with glomerulosclerosis or mesangial hypercellularity. These characteristics related to urinary albumin have already been reported to vary markedly in steroid-responsive nephrotic syndrome of minimal-change nephropathy giving rise to new pathogenetic possibilities in this disease. In the steroid-unresponsive nephrotic children albumin was found to be more microheterogenous and cationic in urine than in serum and at the same time it was conformationally altered. Regarding these characteristics, the selectivity properties of the renal filter are similar in steroid-unresponsive nephrotic syndrome, suggesting a pathogenetic connection between these two renal disorders.

Albuminuria↗

Analysis of cellular populations in peritoneal effluents of children on CAPD.

The characterization of cellular populations in peritoneal effluents (PE) of CAPD patients has been the subject of few studies. In order to establish a possible correlation between PE cells and clinical parameters, we studied the immunocompetent cells that are found in uncomplicated patients. In this study we used cytofluorimetric analysis to characterize phenotypically immunocompetent PE cells. We studied 17 children with a mean age of 8.7 +/- 5.3 years, who had been on CAPD for a mean duration of 16 months. The patients never suffered from peritonitis. The effluents were collected after overnight dialysis and centrifuged to concentrate cells. Surface phenotype of PE cells was tested with a panel of monoclonal antibodies. The analysis of 40 PE samples showed that the various cell types were present with different frequencies, suggesting that a dominant phenotype cannot be defined. The ratio between M3 positive cells (monocytic-macrophagic lineage) and T3 positive cells (T lymphocytes) showed a tendency to decrease after initiation of CAPD. T4/T8 ratio in all samples did not differ from that of peripheral lymphocytes. A high frequency of activated T cells (41% +/- 13), defined by the presence of DR antigens on T3+ M3- cells, was seen in PE and confirmed by the high frequency of T cells expressing the IL-2 receptor.

Adolescent↗

Plasma infusion for hemolytic-uremic syndrome in children: results of a multicenter controlled trial.

The results of a controlled trial to ascertain the usefulness of plasma infusion for the treatment of hemolytic-uremic syndrome (HUS) are reported. Criteria for admission were (1) observation within 8 days from first symptoms, (2) dialysis treatment required, and (3) no special treatments and no more than 25 ml blood/kg previously received. Children were subdivided according to age (less than or more than 3 years) and then randomly assigned to treatment with plasma or symptomatic therapy. Thirty-two children ranging in age from 4 months to 6 years entered this study; 17 received plasma (P+ group) and 15 only symptomatic therapy (P- group). The mean follow-up period was 16 months in both groups. Surgical renal biopsy was performed 29 to 49 days after onset in 11 P+ and 11 P- children, and 33 histologic findings were semiquantitatively evaluated. No death occurred in either group. No differences were found in blood pressure, proteinuria, or hematuria at the end of the follow-up period; in no case were severe arteriolar lesions found. There were no significant differences for the scores of the individual histologic measurements; on electron microscopy, no vascular changes were observed in seven children of the P+ group, whereas in five of seven of the P- group, thickening of the lamina rara interna and arteriolar damage were present. The ability of plasma to stimulate prostacyclin (PGI2) production, measured as its stable derivative 6-keto-PGF1 alpha, was within the normal range for all patients. In our patients with predominant glomerular involvement who were treated in a very early phase of HUS, infusions of plasma did not significantly influence the short- and medium-term clinical outcome and were not effective in severe HUS when given later in the course of the disease. A longer follow-up is needed to ascertain whether the presence of endothelial damage, demonstrated by electron microscopy in children who were not given plasma, is of clinical relevance.

Biopsy↗