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Biomedical subjects

F Perfumo

Publications and source records attributed to F Perfumo.

At least 55 records · Page 3Linked to original sources
PubMed1996

Children on continuous ambulatorial peritoneal dialysis: muscle and plasma proteins, amino acids and nutritional status.

The aim of the study was to investigate plasma and muscle amino acid (AA) levels in children on continuous ambulatory peritoneal dialysis (CAPD) and their relationship to various indices of nutritional status. Ten children with a mean age of 6.4 +/- 5.6 yrs were evaluated. Muscle biopsies and venous blood samples were taken after an overnight fast. Muscle samples were obtained from rectus abdominis. Data were compared with those of a control group of 22 children who were undergoing elective surgery. Informed consent was obtained from the parents. The plasma concentration of most of the essential AA (valine, leucine, isoleucine, lysine, methionine and tyrosine) were significantly reduced and the levels of some non essential AA (aspartic acid, glycine, citrulline, 1-3 methihystidine, taurine + alanine) were significantly higher than in the controls. Muscle intracellular free essential AA concentrations, except the low levels of valine and leucine did not differ significantly from values in the controls. Among non essential AA, aspartic acid, glutamic acid and ornitine showed significantly increased intracellular concentrations. No significant correlations were found between plasma and muscle AA concentration and ASP (alkali-soluble protein)/DNA ratio, serum albumin, transferrin, bicarbonate levels and duration of CAPD. Instead, a significant correlation was noted between the muscle ASP/DNA ratio, an indicator of the amount of cell proteins per cell unit, and age (r = 0.714, p < 0.05). Muscle Branched chain AA levels were significantly correlated to body mass index (BMI) (r = 0.648, p < 0.05).

Adolescent↗
PubMed1996

Effects of peritoneal effluents on mesothelial cells in culture: cell proliferation and extracellular matrix regulation.

Peritoneal fibrosis in patients on peritoneal dialysis is the result of interstitial collagen accumulation within the peritoneal membrane and in mural spaces. Hypothetically, collagen expression by target cells may be regulated by specific endoperitoneal factors, though the existence of such factors has not yet been demonstrated. We evaluated the effects of cell-free peritoneal effluents obtained from six children undergoing peritoneal dialysis on several mesothelial cell functions in vitro. Human peritoneal mesothelial cells (MC) were obtained from the omental tissue of six uraemic children who were undergoing surgery for insertion of a peritoneal catheter. Cells at confluence were utilized to determine cytotoxicity (LDH release), viability (trypan blue), proliferation (3H-thymidine incorporation), collagen expression (3H-proline incorporation, SDS-Page) and mRNA (dot-blot). A preliminary series of experiments, was undertaken to define which of the successive fluid collections during a dialytic procedures induces the greatest changes; this revealed maximal effects of the effluent from the long stasis period. Exposure to peritoneal effluents obtained from four patients with acute peritonitis induced marked changes in cell morphology, stimulated by (3H)-thymidine incorporation into DNA by 300% and upregulated the expression and transcription of type III collagen (6-fold increment in COL3A1 mRNA). Qualitatively but not quantitatively comparable changes in cell proliferation (+100%) and collagen expression were induced by peritoneal effluents from patients without peritonitis. In an effort to reproduce the effect of peritoneal effluents in vitro, we exposed mesothelial cells to various cytokines putatively present in infected peritoneal effluents, namely IL-2, TGF beta and TNF alpha; in no case did we find stimulation of cell proliferation. Finally TGF beta but not TNF alpha or IL2 upregulated collagen synthesis by these cells. These findings demonstrate a direct influence of cell-free peritoneal effluents on mesothelial cell functions, including stimulation of interstitial collagen expression. All these changes were more evident upon exposure to effluents collected during acute peritonitis, which suggests a link between recurrent peritoneal infection and collagen deposition, the most typical precursor of peritoneal fibrosis.

Adolescent↗
PubMed1996

Is the response to rhGH in peritoneal dialysis patients less effective than in patients with chronic renal insufficiency.

Data on the effects of rhGH treatment in children on peritoneal dialysis are limited. In general rhGH therapy seems to be less effective compared with results on patients with chronic renal failure on conservative treatment. Our experience suggests that rhGH can stimulate growth in children on CPD, and that the efficacy of such therapy is reduced after the first year of treatment, although the rhGH is still active.

Child↗
PubMed1995

Antigen-presenting function of human peritoneum mesothelial cells.

Mesothelial cells (MC) from human peritoneal omentum fragments obtained during surgical insertion of peritoneal catheters for continuous peritoneal dialysis in end stage renal failure (ESRF) patients were cultured in vitro. MC exhibited a phenotype different from macrophages, but MHC class II molecules were well expressed. Therefore MC lines were tested for antigen-presenting capacity by pulsing with soluble antigens (tetanus toxoid and purified protein derivative (PPD)) or with a corpusculate antigen (Candida albicans bodies). Autologous peripheral blood mononuclear cells (PBMC) depleted of adherent monocytes and cloned T cells generated from an individual matched for the MHC class II antigen DR2 were used to test antigen-presenting function. MC effectively presented the soluble and corpusculate antigens to autologous and MHC-compatible allogeneic lymphocytes, indicating that they are endowed with both endocytic/phagocytic activity and with processing/presenting capacity. Preincubation of MC with human recombinant interferon-gamma (IFN-gamma) up-regulated MHC class II and intercellular adhesion molecule-1 (ICAM-1) expression, but the effect on antigen-presenting function was not consistent. Since MC are an important component of the peritoneal environment, they may participate, along with macrophages, in activation of specific T cells and in the generation of local cell-mediated immunity to various pathogens.

Adolescent↗
PubMed1995

Clinical experience in the treatment of infants with chronic peritoneal dialysis.

Chronic peritoneal dialysis (CPD) is the first treatment modality for most infants with end-stage renal failure; this group of patients shows peculiar clinical and technical problems. We present the data from a National Registry on 22 children starting CPD under one year of age, representing 11.6% of the total population of the Registry (189 patients). Mean weight at start of CPD was 6.1 +/- 1.8 kg and duration of dialysis was 22.1 +/- 15.5 months. During the follow-up period, 9 patients were transplanted, 1 was shifted to hemodialysis, and 4 died. Patient survival was 89.1% and 82.2% at 1 and 2 years (97.9% and 96.5% in the group of 167 older children); technique survival results were 89.1% at 1 year and 77.1% at 2 years (vs 92.5% and 85.7%, respectively). The incidence of peritonitis was 1 episode every 15.6 CPD-months (1:16.1 in the older children). Catheter-related complications occurred more frequently in infants (1:11.8 vs 1:17 episode:CPD-months), even if this difference was not statistically significant. Statural growth was on average -0.29 +/- 0.66 SD/year with a significant improvement between the first (-0.50 +/- 0.79) and the second (+0.23 +/- 0.77) year of CPD. Our data confirm that infants represent a higher risk group and that they can be treated satisfactorily with CPD while awaiting renal transplantation.

Catheters, Indwelling↗
PubMed1994

Cyclosporine enhances the synthesis of selected extracellular matrix proteins by renal cells "in culture". Different cell responses and phenotype characterization.

Glomerulosclerosis and interstitial fibrosis are 2 major side effects of protracted therapy with CsA in heart transplant patients and in nonrenal immunologic diseases. To investigate whether there is any cause-effect correlation between CsA and the synthesis of extracellular matrix in the kidney, we determined the amount and composition of collagens produced by various renal cells "in culture" upon exposure to increasing levels of CsA. The cellular models we used included primary cultures of both human and rat mesangial cells (hMC, rMC), human and rat renal fibroblasts (hFib, rFib), and human tubular epithelia as well as cell lines of rat renal fibroblasts (NRK49F) and of tubular epithelia (NRK52E). In the case of primary cell cultures, CsA induced a marked increment of total collagen synthesis. This was highest for renal fibroblasts (+330% hFib, +110% rFib), followed by rMC (+170%), hMC (+100%), and human tubular epithelia (+130%). At the highest dosage of CsA (5 ng/ml), this corresponded to a net increment in collagen III synthesis by both hMC and hFib (+150% and +300%), while collagen I and collagen IV were unaffected. On hMC, CsA also induced a maximal increase in a component with 70 kDa molecular mass, which was produced only in a negligible amount by these cells in standard conditions. This low molecular mass collagen was tentatively characterized by cyanogen-bromide digestion and fingerprint analysis as a novel molecule showing a peptide composition without comparable features for any reported collagen map. NRK49F and NRK52E cell lines were not affected by CsA. Taken together, these observations demonstrate that CsA is able to induce the synthesis of specific collagens, mainly of collagen III and of a 70-kDa component, by various renal cells in cultures. Since the same cells are the renal site of production of extracellular matrix in pathological conditions, we hypothesize that this effect is a relevant one in the pathogenesis of glomerulosclerosis/interstitial fibrosis during protracted therapies with CsA.

Animals↗
PubMed1994

Selective enhancement by cyclosporin A of collagen expression by mesangial cells 'in culture'.

Extracellular matrix deposition in mesangial areas leading to glomerulosclerosis is the major side effect of protracted therapies with cyclosporin A. In order to define any direct correlation between a chronic therapy with the drug and glomerulosclerosis we studied the effects of cyclosporin A on extracellular matrix production by human mesangial cells in culture. By immunoprecipitation and sodium dodecyl sulfate polyacrylamide electrophoresis (SDS-PAGE) of [3H]proline-labeled mesangial cells it was found that cyclosporin A induced a dose-dependent increase in total collagen synthesis (+80%), corresponding to a net increment in collagen III (+120%) and in a component with 70 kDa molecular weight which was produced only in negligible amount by mesangial cells under standard conditions. This collagen was characterized by cyanogen bromide digestion and finger print analysis as a novel molecule, not sharing any peptide composition similarities with the already characterized collagens. These data indicate that cyclosporin A stimulates the synthesis by mesangial cells of selected collagens, mainly collagen III and a new low molecular weight component. This mechanism may be relevant in cyclosporin A induced glomerulosclerosis occurring during protracted therapies with the drug.

Antibody Specificity↗
PubMed1994

Protracted high-dose interferon gamma therapy for chronic experimental nephropathy.

This study focused on the utility of interferon gamma (IFN gamma) as an anti-fibrotic drug in renal experimental fibrosis; the nephropathy was induced by two doses of Adriamycin (ADR) in 20 Sprague Dawley rats, 10 of which were randomly assigned to receive IFN gamma (45,000 UI) on alternate day for 16 weeks. At the end of the follow up, ADR rats treated with IFN gamma developed massive proteinuria, slight renal insufficiency, and presented diffuse glomerulosclerosis, tubulo interstitial infiltration and fibrosis. No difference was found in the composition of tubulo-interstitial infiltrates, mainly consisting in CD4+T lymphocytes with a minor component of CD8+T cells, in comparison with rats treated with ADR alone. These observations demonstrate the inefficacy of a protracted high-dose treatment with IFN gamma in chronic experimental nephropathy with interstitial fibrosis.

Animals↗
PubMed1994

Community-wide outbreak of hemolytic-uremic syndrome associated with non-O157 verocytotoxin-producing Escherichia coli.

From 20 April through 13 May 1992, 9 children were hospitalized with hemolytic-uremic syndrome in Lombardia, Italy, where only 14 cases of this syndrome had occurred in the preceding 4 years. Cases were scattered in a large area encompassing five provinces, and the source of the outbreak was not identified. Eight patients needed dialysis, and there was 1 death. Seven of the 9 cases were examined for evidence of infection by Vero cytotoxin (VT)-producing Escherichia coli (VTEC). Six children had serum antibodies to the lipopolysaccharide of E. coli O111, and a VT-producing E. coli O111:NM was isolated from stool in 1 case. This is the first outbreak of VTEC infection recognized in Italy and the first associated with an E. coli serotype other than O157:H7.

Antibodies, Bacterial↗
PubMed1994

Intact renal albumin downregulates the extracellular matrix expression by mesangial cells and renal fibroblasts in vitro.

Chronic Adriamycin (ADR) nephropathy is invariably associated with glomerulosclerosis and tubulointerstitial fibrosis. To investigate the hypothesis that severe albuminuria plays a role in the pathogenesis of both processes, we purified the protein from conditioned media of rats with advanced ADR nephropathy and tested the fibrogenic effect on renal fibroblasts and mesangial cells in vitro. Albumin was purified by pseudoligand chromatography and was identified on the basis of the NH2 amino terminus. Furthermore, it was differentiated from the urinary homologue, being more anionic and more fatted while maintaining a conserved peptide composition. The exposure of renal cells to renal albumin induced a dose-dependent reduction in collagen synthesis with a half-maximal decrease with 0.2 microgram/ml of albumin. With renal albumin levels of 0.4 microgram/ml the collagen incorporation of 3H-proline by mesangial cells and renal fibroblasts (primary cultures and cell lines) was reduced by 76, 81 and 45% respectively. A qualitative analysis by SDS-polyacrylamide electrophoresis and immunoprecipitation of radiolabelled collagens demonstrated a drastic and unselective decrease in all major collagens synthesized by mesangial cells and fibroblasts, including type I, III and V. Previous immunoprecipitation of the protein with anti-rat albumin antibodies completely reversed this phenomenon. Finally, albumin purified from urines of rats with ADR nephropathy downregulated the synthesis by renal cells of the same collagens but this effect was less evident compared to renal albumin. These findings demonstrate that renal albumin drastically reduces the synthesis of collagens by mesangial cells and renal fibroblasts, this effect being most evident on those components which constitute the extracellular matrix in glomerulosclerosis and interstitial fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗
PubMed1994

Muscle and plasma amino acids and nutritional status in kidney-transplanted children.

Nutritional status, assessed by anthropometric and biochemical methods, protein and amino-acid (AA) composition and muscle water were evaluated in 11 kidney transplanted children and in a control group of 10 children with normal renal function who were undergoing elective surgery. Samples of the rectus abdominis muscle were taken when surgery was performed in the control children and when the peritoneal catheter was removed in the transplanted children. The mean time from the transplantation to the study time was 97 +/- 14 days (range 72-114 days). Height was reduced in the transplanted children compared to the controls but skinfold thickness, arm muscle circumference and serum proteins (total protein, albumin, transferrin, pseudocholinesterase) were normal. The body mass index was over the 50 degree percentile in nine of the eleven children. The muscle contents of total, extracellular, and intracellular water, alkali-soluble protein (ASP), DNA and the ASP/DNA ratio were not significantly different in transplanted children from those in the controls. Plasma leucine and taurine levels were significantly decreased, whereas plasma citrulline and alanine levels and the glycine/serine ratio were increased. Muscle threonine, alanine+taurine, glycine and aspartic acid levels as well as the glycine/serine ratio were increased in the transplanted children. Transplanted children show an almost normal muscle AA profile and a plasma AA pattern that seems to be related to the prednisone therapy.

Adolescent↗
PubMed1994

A multicenter study on the hospitalization of pediatric patients on chronic peritoneal dialysis.

The Italian Registry of Pediatric Chronic Peritoneal Dialysis (CPD) carried out a special study on patient hospitalization during the years 1989-1992. Ninety-two children (mean age 8.4 +/- 4.7 years) entered the study, for a total of 1406 CPD-months. The contribution of the different causes of hospitalization for a total of 4683 hospital days was: CPD training 31%; routine controls 14%; CPD-related complications 35%; clinical complications 14%; other causes 6%. The rate of patient hospitalization that resulted was 3.33 days/CPD-month; it was higher in the first year (4.32 days/CPD-month) than in the second year (1.64 days/CPD-month) or in the third year (2.25 days/CPD-month). This difference was mainly due to the need for the training at the start of the CPD treatment. The evaluation of the hospitalization rate in different age groups showed a statistically significant difference (p < 0.05) between the group 0-2 years (5.47 days/CPD-month) and the group 3-15 years (2.78 days/CPD-month). Complications were the cause of 150 admissions to the hospital (1:9.6 CPD-months). Ninety-eight admissions were due to CPD-related complications: peritonitis (33%), problems with the catheter (19%), abdominal hernias (4%), and others (9%). Among clinical complications (52 admissions), the main cause of hospitalization was hypertension (15%), followed by infections (4%), and malnutrition (3%).

Adolescent↗