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M L Degl'Innocenti

Publications and source records attributed to M L Degl'Innocenti.

7 recordsLinked to original sources

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↗

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↗

[Role of echo-Doppler in the screening of renal artery stenosis in children with kidney transplants].

Renal artery stenosis (RAS) in renal transplanted pediatric patients is a long-term complication. The clinical suspicion must be considered when patients exhibit signs of impaired renal function or refractory hypertension, not associated with other complications of renal transplantation -i.e., acute or chronic rejection, glomerulonephritis, cyclosporine toxicity. The intermediate step between clinical suspicion and angiography is represented by Doppler US. The authors report their experience with Doppler US in the screening of RAS in a pediatric series of transplanted patients. The incidence of RAS in our series (54 transplanted kidneys, 46 of them included in the study) was 4.3%. A severe stenosis was demonstrated by both Doppler US and angiography in 2 patients, with 100% Doppler sensitivity. In both stenoses, Doppler US showed high systolic peaks (blood flow velocity > or = 2.5 m/s) and post-stenotic turbulence. Thanks to its high sensitivity, Doppler US is considered to be very useful in the screening of vascular complications in renal transplanted children.

Adolescent↗

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↗

Effect of a single daily dose treatment of fenofibrate on plasma lipoproteins in hyperlipoproteinaemia IIb.

The safety and efficacy of a single daily dose of fenofibrate (200 mg) have been evaluated in 12 Type IIB hyperlipidaemic patients in a three-month study. At the same time the pharmacokinetics was studied to check whether this new dosage schedule would give a therapeutic plasma levels of fenofibrate. At the single daily dose of 200 mg, fenofibrate was highly effective, very well tolerated, and it reached therapeutic plasma levels without accumulation. It appears that fenofibrate can usefully be employed at this dosage in hyperlipidaemia, especially since patient compliance is better when only one daily dose need be taken.

Adult↗