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Biomedical subjects

L Peruzzi

Publications and source records attributed to L Peruzzi.

At least 19 recordsLinked to original sources
PubMed2004

Are allopurinol and metabolites found in HPRT deficient erythrocytes responsible for increased NAD synthesis?

Aim of this study was to ascertain whether allopurinol, usually administered to hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficient patients, or metabolites abnormally increased in HPRT deficient erythrocytes (NAD, PPribP) could be directly responsible for the reported increased activities of nicotinic acid phosphoribosyltransferase (NAPRT) and NADsynthetase (NADs) in these patients. No direct effect of the mentioned metabolites was demonstrated.

Allopurinol↗
PubMed2001

Polymorphisms in the promoter region and at codon 54 of the MBL2 gene are not associated with IgA nephropathy.

BACKGROUND: IgA nephropathy (IgAN) occurs sporadically in unrelated individuals. Several different polymorphic genes have been investigated in recent years in order to demonstrate their possible association with IgAN. Three recent, different studies with conflicting conclusions have discussed the role of the mannose binding lectin (MBL), a serum lectin involved in natural immunity, in the IgAN pathogenesis by examination of MBL deposits in biopsies. In the present study we investigated several polymorphisms of the MBL gene located in the promoter region and in the first exon. METHODS: MBL polymorphism detection was performed in 22 Italian patients with familial IgA nephropathy and in 138 Italian patients with the sporadic form of the disease. The polymorphisms in the MBL2 promoter region and in the exon 1 were investigated, respectively, by direct sequencing and by amplification refractory mutation system-polymerase chain reaction on genomic DNA collected from peripheral blood. Seventy-four unrelated healthy subjects matched for ethnic origin were used as controls. RESULTS: Allelic and genotypic frequencies of the polymorphisms at position -550, -328, -221 and at codon 54 did not show any differences between patients and controls. Similar frequency distributions of these polymorphisms were also found in the subgroups of IgAN patients subdivided according to the clinical manifestations and the progression of the disease. CONCLUSIONS: This study indicates that the analysed polymorphisms of the MBL gene do not appear to be primarily involved in the susceptibility and severity of IgAN.

Adolescent↗
PubMed2001

[Neonatal chronic kidney failure associated with cyclo-oxygenase-2 inhibitors administered during pregnancy].

Non-steroidal anti-inflammatory drugs (NSAID) are used since years as tocolytic due to their capacity to inhibit cyclo-oxygenase (COX) expressed in uterus and fetal membranes, fundamental for labour initiation and maintenance. The use of nimesulide, a COX-2 selective NSAID, has been recently proposed due to its capacity to selectively inhibit the enzyme expressed in the myometrium and endometrium. A case of neonatal irreversible end stage renal failure after maternal assumption of nimesulide as tocolytic for 6 week is reported. Cesarean section at the 32nd week due to oligohydramnios gave birth to a baby girl of 2090 g, in good general conditions, without signs of respiratory distress and of visible abnormalities. From birth she displayed oligo-anuria which required dialytic substitutive therapy from the second day of life. At US scan both kidneys had normal diameters for gestational age slightly increased echogenicity and a reduced cortico-medullary differentiation. On the 20th day of life she had a surgical renal biopsy for the persistence of oligo-anuria, showing fetal glomeruli, without lymphocytic interstitial infiltrate, and normal tubuli without evidence of necrosis. She is now 16 months old and under automated peritoneal dialysis on a home dialysis program. The occurrence of chronic renal failure in strict relationship with maternal nimesulide assumption in this case is strongly suggestive for a pharmacological damage, either direct or mediated by renin angiotensin inhibition, and possibly modulated by genetic factors, likely to account for the different outcome of similarly treated patients. A cautious use of this drug as long term tocolytic should be recommended while waiting for ad hoc experimental and clinical evidences of safeness.

Adult↗
PubMed2000

Cytosolic 5'-nucleotidase hyperactivity in erythrocytes of Lesch-Nyhan syndrome patients.

Lesch-Nyhan syndrome is a metabolic-neurological syndrome caused by the X-linked deficiency of the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT). Metabolic consequences of HGPRT deficiency have been clarified, but the connection with the neurological manifestations is still unknown. Much effort has been directed to finding other alterations in purine nucleotides in different cells of Lesch-Nyhan patients. A peculiar finding was the measure of appreciable amount of Z-nucleotides in red cells. We found significantly higher IMP-GMP-specific 5'-nucleotidase activity in the erythrocytes of seven patients with Lesch-Nyhan syndrome than in healthy controls. The same alteration was found in one individual with partial HGPRT deficiency displaying a severe neurological syndrome, and in two slightly hyperuricemic patients with a psychomotor delay. Since ZMP was a good substrate of 5'-nucleotidase producing Z-riboside, we incubated murine and human cultured neuronal cells with this nucleoside and found that it is toxic for our models, promoting apoptosis. This finding suggests an involvement of the toxicity of the Z-riboside in the pathogenesis of neurological disorders in Lesch-Nyhan syndrome and possibly in other pediatric neurological syndromes of uncertain origin.

5'-Nucleotidase↗
PubMed2000

Normal values of the bioelectrical impedance vector in childhood and puberty.

The purpose of this study was to determine the reference, bivariate, and tolerance intervals of the whole-body impedance vector in Italian children. This was a cross-sectional, multicenter study, and participants were chosen from the general school population. The impedance vector (standard, tetrapolar analysis at 50-kHz frequency) was measured in 3110 subjects, ages 2 to 15 y, and 2044 healthy children (1014 male and 1030 female) with weight and height within the 95th percentile were selected for the analysis (resistance-reactance graph method). The age-specific 95% confidence intervals of mean vectors and the 95%, 75%, and 50% tolerance intervals for individual vector measurements were plotted using resistance and reactance components standardized by the subject's height. Mean vectors from both sexes with separate 95% confidence ellipses were considered as representative of eight different age groups, from 2 to 13 y. There was a statistically significant sex effect on vector distribution from boys and girls in the age group of 14 to 15 y. The impedance vector distribution of children was also compared with healthy adult subjects (354 male and 372 female, age 15 to 85 y). There was a progressive, statistically significant vector shortening from age 2 to 15 y toward the adults' vector position. In conclusion, we established the trajectory followed by the mean impedance vector in children over ages 2 to 15 y and also obtained the reference, bivariate, and 95%, 75%, and 50% tolerance intervals of the impedance vector by age for healthy children, with which the vectors from children with altered body composition can be tested.

Adolescent↗
PubMed2000

Integrin expression and IgA nephropathy: in vitro modulation by IgA with altered glycosylation and macromolecular IgA.

BACKGROUND: Signal transduction by mesangial cell (MC) integrins regulates cell growth and survival, extracellular matrix production, and organization. The aim of the study was to investigate human MC integrin modulation by differently glycosylated IgA and macromolecular IgA, which are thought to play a pathogenetic role in IgA nephropathy (IgAN). METHODS: MCs were incubated with purified human polymeric IgA, heat-aggregated IgA, IgA glycoforms generated by enzymatic hydrolysis of saccharide residues and serum fractions from IgAN patients, and controls isolated by lectin affinity and containing IgA with peculiar glycan patterns. Integrins were quantitated by flow cytometry. RESULTS: Cultured MCs highly expressed alphavbeta3 and some alpha3beta1; alphavbeta3 was up-regulated by matrix components (P < 0.02). In vitro desialylated and degalactosylated polymeric human IgA enhanced alphavbeta3 expression on cultured MCs (P < 0.001). Serum IgA glycoforms isolated from IgAN patients with high exposure of internal sugars, GalNAc, Neu5Ac2,6GalNAc, and Man enhanced alphav expression on cultured MCs more than healthy controls. CONCLUSIONS.: These data support the hypothesis that IgA glycation plays a role in modulating the cell-matrix interaction, and that this mechanism can be operating in IgAN.

Antibodies, Monoclonal↗
PubMed2000

Aberrantly glycosylated IgA molecules downregulate the synthesis and secretion of vascular endothelial growth factor in human mesangial cells.

To gain insight into the glomerular capillary repair mechanisms in immunoglobulin A (IgA) nephropathy, we focused on vascular endothelial growth factor (VEGF-A) and nitric oxide (NO). Because abnormal glycosylation of serum IgA has been shown in IgA nephropathy, we examined whether VEGF-A and NO production by mesangial cells (MCs) could be modulated by aberrantly glycosylated (desialylated or degalactosylated) IgA. VEGF-A and NO synthase (NOS) gene expression were examined by reverse-transcriptase polymerase chain reaction (RT-PCR) or Northern blot analysis, and VEGF-A peptide, by capture enzyme-linked immunosorbent assay and NOS activity as production of tritium ([(3)H]) citrulline from [(3)H] arginine. Semiquantitative densitometric analysis of RT-PCR experiments showed a significant downregulation of VEGF-A messenger RNA (mRNA) in MCs incubated with aberrantly glycosylated IgA. This resulted in decreased release of VEGF-A in culture medium (P: < 0. 01). NOS activity and inducible NOS (iNOS) mRNA were enhanced by aberrantly glycosylated IgA (both P: < 0.01). No modulation of constitutive NOS mRNA was found. The depression of the VEGF-A production induced by aberrantly glycosylated IgA was mediated by NO because it was completely reversed by the NOS inhibitor, N:omega-nitro-L-arginine methyl ester. The NO donor, sodium nitroprusside, induced a bimodal modulation of VEGF; although low concentrations (0.0001 nmol/L) increased VEGF-A synthesis, greater concentrations (1,000 nmol/L) depressed it. In conclusion, we report negative control of VEGF-A synthesis in MCs by aberrantly glycosylated IgA, mediated by enhanced iNOS activity. We speculate that both increased iNOS activity and depressed VEGF-A synthesis might have a role in impairing vascular repair and favor sclerosis in IgA nephropathy.

Down-Regulation↗
PubMed2000

[Treatment of fluid overload and kidney failure with periotoneal dialysis after heart surgery].

BACKGROUND: Infants undergoing cardiac surgery with prolonged cardio-pulmonary bypass are particularly exposed to the risk of acute renal failure for renal hypoxia due to low cardiac output. METHODS: To limit fluid overload deriving from oligo-anuria and low cardiac output we have recently adopted an early peritoneal dialysis protocol, positioning the peritoneal catheter during the intervention and performing early exchanges at first signs of inadequate diuretic response and/or "leaky capillary syndrome" with diffuse edema. From 1-1 to 31-12-1997 12 patients (8 males), of median age of 65.5 days (range 1-350 days) and median weight of 3463 g (range 2380-6550 g) were treated with peritoneal dialysis (automated exchanges of 10 ml/kg body weight of 1.5% glucose, dwell time 20 minutes). Cardiac pathologies included complex hearth malformations. Cardiopulmonary bypass lasted a mean of 202 minutes (range 102-372 minutes). The children were treated for a minimum of 1 to 42 peritoneal dialysis sessions. The infusional therapy included human albumin and fresh frozen plasma to substitute losses and furosemide at the dose of 4 mg/kg/day to reduce the "leaky capillary syndrome". RESULTS: The results were very satisfactory: only 3 children died in the first 30 days after surgery. Renal function was normal at the end of the observation in 8/12 cases, and 2 cases presented chronic renal failure. CONCLUSIONS: Since similar series report a mortality rate of 33-79%, it is suggested that early peritoneal dialysis may have positively influenced the final survival rate.

Cardiopulmonary Bypass↗
PubMed1999

Hypoxanthine-guanine phosphoribosyltransferase deficiency and erythrocyte synthesis of pyridine coenzymes.

Purine and pyridine metabolism were studied in ten Lesch-Nyhan patients, with virtually no hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity in erythrocytes. Increased NAD erythrocyte concentrations were found in all patients. Raised activities of two enzymes catalysing NAD synthesis from nicotinic acid (nicotinic acid phosphoribosyltransferase: NAPRT, and NAD synthetase: NADs) was found in erythrocyte lysates from all patients. The two enzymes had normal apparent Km for their substrates and increased Vmax. The rate of synthesis of pyridine nucleotides from nicotinic acid by intact erythrocytes in vitro was also increased in most patients. These findings suggest that raised NAD concentrations in HPRT- erythrocytes are due to enhanced synthesis as a result of increased enzyme activities.

Adolescent↗
PubMed1999

Accidental hypothermia in a child.

We report a case of severe accidental hypothermia (24.8 degrees C) in a seven-year-old child due to prolonged exposure to low temperatures and temporary contact with river water. When the patient was seen in hospital, bradycardia (30.min-1), bradypnoea (5. min-1), scarcely reacting pupils, and Glasgow Coma Scale=3 were noted. For rewarming minimally invasive techniques (humidified warmed gases and intravenous solutions at 40 degrees C) were employed with a very successful outcome.

Accidents↗
PubMed1998

Polymorphisms in angiotensin-converting enzyme gene and severity of renal disease in Henoch-Schoenlein patients. Italian Group of Renal Immunopathology.

BACKGROUND: The influence of angiotensin converting enzyme (ACE) gene polymorphism on the progression of primary IgA nephropathy (pIgAN) is still debated. Even though the allele frequency was reported to be similar to controls, in some studies D/D patients had a faster decline of renal function and need of dialysis. Since Henoch-Schoenlein purpura (HSP) nephritis is considered a systemic vasculitis with renal lesions indistinguishable from pIgAN, we investigated the effect of the ACE polymorphism on presentation and progression of HSP IgAN. METHODS: We examined the insertion (I) and deletion (D) polymorphism in intron 16 of ACE gene by PCR amplification of genomic DNA of 82 patients (37 children), with biopsy-proven IgAN associated with HSP enrolled in a collaborative study. RESULTS: No significant association with clinical presentation at onset or with final outcome was found (functional impairment at outcome in 31.8%, D/D, 27.4%, I/D and 44% I/I, heavy proteinuria in 36.3% D/D, 21.6% I/D, and 11.1% I/I). Patients homozygous for the D allele had a greater number of extrarenal relapses (P=0.0028). No association was found between the ACE genotype and the presence of hypertension at onset and at the end of the follow-up. No difference was found between adults and children. CONCLUSIONS: In this cohort of HSP IgAN, no ACE I/D polymorphisms were found to be associated with progressive deterioration of renal function. Different genes possibly involved in vasculitis might more strictly modulate expression and evolution of HSP IgAN.

Adolescent↗
PubMed1997

Nonenzymatically glycated albumin (Amadori adducts) enhances nitric oxide synthase activity and gene expression in endothelial cells.

Hyperglycemia is considered to induce diabetic nephropathy through nonenzymatic glycation of proteins. Since hyperfiltration is likely to be the mechanism initiating the glomerular lesions, we investigated the effects of Amadori glucose adducts in serum albumin on the production of vasoactive mediators, including nitric oxide (NO) and eicosanoids, by endothelial cells (EC). Amadori adducts of glycated albumin induced a dose-response increase in NO synthase activity of murine endothelioma cells, up to 16.4 +/- 2.1-fold increase of basal values (P < 0.0001) at concentrations of 35 mg/ml mimicking physiological serum albumin concentration, and 4.6 +/- 0.8-fold increase at 17 mg/ml (P < 0.001). The effect was still detectable with glycated albumin 1.7 mg/ml, which approaches its estimated concentration in diabetic serum (1.6 +/- 0.3-fold increase, P < 0.05) The phenomenon was reproducible in human umbilical vein endothelial cells, though to a lesser extent, and further studies on murine EC were employed. The mRNA encoding for inducible NO synthase was overexpressed in EC incubated with Amadori adducts of glycated albumin in comparison to native albumin. Glycated albumin induced increased mRNA expression and synthesis of TNF-alpha. The stimulatory effect induced by glycated albumin on NO synthase activity was almost completely inhibited by anti TNF alpha antibodies. 3H-thymidine incorporation by EC was significantly inhibited when cells were grown in presence of glycated albumin (P < 0.001), and the phenomenon was abolished by the coincubation of the NO competitive inhibitor L-NAME. The early glycosylation products increased thromboxane production (P < 0.001), while prostaglandin E2 synthesis was unaffected. These data indicate that Amadori products of glycated albumin modulate NO synthase activity and eicosanoid balance in EC. These effects may be relevant to the hemodynamic changes in the early phases of diabetic nephropathy and in the lasting progression to sclerosis.

Albumins↗
PubMed1997

Acetate intolerance is mediated by enhanced synthesis of nitric oxide by endothelial cells.

The clinical picture of acetate intolerance strictly mimics the nitric oxide (NO) effect, including smooth muscle relaxation and extreme vasodilation. Because acetate induces production of cAMP, which is a powerful stimulus of NO synthase (NOS), we evaluated the effect of different dialysate solutions with and without acetate on NOS activity in endothelial cells (EC). NOS activity of EC, evaluated as H3-citrulline produced from H3-arginine, was modulated by the dialysate composition (e.g., 38 mmol/L acetate produced an increase of 3.2 +/- 0.39-fold compared with basal values (P < 0.0005), and the small amount of acetate (4 mmol/L) in 35 mmol/L bicarbonate solution increased the NOS activity by 2 +/- 0.49-fold (P < 0.05). Conversely, the acetate-free solution produced no effect on NOS activity. The mRNA encoding for inducible NOS was highly expressed in EC incubated with acetate buffer and also with acetate in bicarbonate dialysis buffer. The EC proliferative index was depressed by acetate (P < 0.0005), and tumor necrosis factor synthesis was increased (P < 0.0005) compared with acetate-free buffer. This study suggests that dialytic "acetate intolerance" can be induced by the activation, through cAMP and tumor necrosis factor release, of NOS. The small amount of acetate in bicarbonate dialysate, although capable of inducing in vitro NOS activation, is likely to be rapidly metabolized, whereas the large amounts of this anion in acetate fluids overwhelm metabolism by the liver. Acetate-free dialysate is the only solution that provides an acceptable level of biocompatibility both in vivo and in vitro.

Acetates↗
PubMed1996

Tubulointerstitial responses in the progression of glomerular diseases: albuminuria modulates alpha v beta 5 integrin.

Proteinuria represents one of the most unfavorable prognostic factors in the progression of nephropathies. Several lines of evidence support a role for proteinuria per se in the development of interstitial fibrosis, albeit the molecular mechanisms are still unknown. We investigated the potential role of integrins expressed on tubular cells in regulating the synthesis and organization of interstitial matrix or as mediators of tubulointerstitial damage in conditions mimicking the nephrotic milieu. Under basal conditions, cultured tubular cells highly expressed alpha 3 beta 1 and, at focal contacts, alpha v beta 3. In contrast, alpha v beta 5 was weakly and diffusely distributed all over the plasma membrane. Cultures on a variety of matrix substrates (fibronectin, laminin, collagen types I and IV, vitronectin, von Willebrand factor, fibrinogen) did not induce any phenotypic change in integrin expression by tubular cells. Conversely, the addition of albumin resulted in a highly increased membrane expression of beta 5, which was organized in typical focal contacts and was related to the dose of albumin added. Immunofluorescence, flow cytometry, immunoprecipitation and RT-PCR experiments argue for a complex mechanism that includes increased post-transcriptionally regulated protein synthesis, accelerated conversion of precursors to mature forms, and increased surface delivery to discrete adhesive structures. Up-regulation of the beta 5 chain in tubular cells was confirmed in 9 out of 11 kidney biopsies from proteinuric glomerulonephritides including membranous and focal sclerosing glomerulonephritis, while it was not expressed in nonproteinuric kidneys including five biopsy specimens. This is the first report indicating that proteinuria up-regulates the surface expression and distribution of a specific integrin chain on tubular cells. These observations suggest the participation of integrins in a hitherto unexplored mechanism of tubulo-interstitial responses to glomerular injury.

Albuminuria↗
PubMed1996

Adriamycin-induced proteinuria in nude mice: an immune-system-mediated toxic effect.

BACKGROUND: The renal minimal lesion disease induced in rats by adriamycin (ADR) is generally thought to be consequent to a direct cytotoxic effect of this drug on glomerular epithelial cells. Only recently an altered synthesis of mediators, including reactive oxygen species and monocyte-macrophage cytokines, has been hypothesized. METHODS: A mouse strain (nude) bearing a congenital thymic aplasia is a suitable experimental animal to evaluate the role of immune reactions in the development of the ADR nephropathy, provided mouse susceptibility to its toxic effect. Therefore, experimental mice were divided into three groups (G) each receiving adriamycin 7.5 mg/kg b.w.: GA (15 heterozygous nu/O mice with normal immune system); GB (15 homozygous nu/nu athymic mice); GC (15 homozygous nu/nu mice which were also splenectomized, irradiated, and treated with anti-asialo Gm1 antibody to abolish NK and decrease macrophage activity). All animals were maintained under pathogen-free conditions. Urinary proteins, albumin and TNF-alpha excretion were measured. RESULTS: After 14 days the proteinuria was 43.8+/-1.7 microg/min in GA, 30.2+/-2.9 microg/min in GB (P<0.05) and 12.2+/-2.8 microg/min in GC (GA vs GC, P<0.0001; GB vs GC, P<0.05). Albuminuria gave a similar profile. TNG-alpha urinary excretion was significantly higher in GA (17.3+/-3.2 mU/min) than in GB (5+/-0.6 mU/min, P<0.001) and GC (3.2+/-0.9 mU/min, P<0.001). A significant correlation was found in GA between urinary TNF-alpha and protein losses (r2=0.63 P<0.0001). Kidney tissue homogenates failed to show in each experimental group any evidence of mRNA encoding for TNF-alpha, which was detectable in peripheral mononuclear cells from GA and GB, but undetectable in GC mice. Segmental effacements of glomerular epithelial cell foot process were observed by electron-microscopy in GA only, while they were minimal in GB and absent in GC. Iron colloidal staining for anionic sites on frozen sections always showed a normal pattern. CONCLUSIONS: Nude mice bearing cellular immunity deficiency are protected from proteinuria following ADR toxicity. An impaired synthesis and release of lymphomonocyte mediators including TNF-alpha could be envisaged.

Animals↗
PubMed1995

A possible role for nitric oxide in modulating the functional cyclosporine toxicity by arginine.

The renal damage consequent to cyclosporine A (CsA) administration ranges from hemodynamic alterations to irreversible chronic lesions. The initial vasoconstriction depends upon the imbalance between the various modulators of the renal vascular tone, among which the most powerful are endothelins and nitric oxide (NO). CsA could play a crucial role by inhibiting the Ca++/calmodulin-mediated activation of the constitutive NO synthase (NOS) isoform, which converts L-arginine (L-Arg) into NO and citrulline, with a 1:1 stoichiometry. To investigate the possibility of modulating CsA nephrotoxicity with L-Arg we studied six groups (G) of Lewis rats treated with daily gavage up to eight weeks: G1, CsA 40 mg/kg; G2, G1 plus L-Arg 300 mg/kg; G3, G2 plus the competitive inhibitor of NOS, NG-nitro-L-Arg (L-NNA); G4, L-Arg alone; G5, L-NNA alone; and G6, controls receiving vehicle alone. After eight weeks L-Arg treated rats were protected against the toxic effects of CsA [creatinine (Cr) values, G2, 0.62 +/- 0.05 mg/dl vs. G1, 0.99 +/- 0.16 mg/dl, P < 0.001; proteinuria (P), G2, 7.2 +/- 1.02 mg/day vs. G1, 15.1 +/- 1.9 mg/day, P < 0.01]. The administration of L-NNA abolished the protective effect of L-Arg (G3, Cr 1.23 +/- 0.16 mg/dl; P 16.9 = 2.3; P < 0.02 and P < 0.005, respectively vs. G2). The levels of Cr in G2 rats were superimposable to control groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗