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Biomedical subjects

A Dal Canton

Publications and source records attributed to A Dal Canton.

At least 19 recordsLinked to original sources
PubMed2006

Influence of methylprednisolone on plasma homocysteine levels in cadaveric renal transplant recipients.

The aim of the present study was to investigate plasma homocysteine levels in renal transplant recipients in the course of steroid-based or steroid-free immunosuppression. Data from 32 patients were retrospectively analyzed according to the steroid immunosuppressive regimen. The 20 recipients on methylprednisolone (MP) plus cyclosporine (CyA) or tacrolimus (TRL) (n = 20) showed similar creatinine levels when compared with those on calcineurin inhibitors plus mycophenolate mofetil (MMF; n = 12), (1.6 +/- 1.5 vs 1.6 +/- 0.4 mg/dL; P = NS) but significantly higher total plasma homocysteine (tHcy) levels (28.5 +/- 12.5 vs 16.3 +/- 5.5 micromol/L; P < .05). No differences of tHcy levels have been observed when patients were analyzed according to CyA- or TRL-based immunosuppression regardless of MP or MMF associations. Our data suggest that recipients, particularly those on steroid-based immunosuppression, should receive homocysteine-lowering treatment early after transplantation.

Adult↗
PubMed2005

A randomized trial of steroid avoidance in renal transplant patients treated with everolimus and cyclosporine.

In this randomized trial renal transplant recipients were treated with basiliximab, everolimus 3 mg/day, low-dose CsA. At transplantation, patients were randomized to stop steroids at the seventh day (group A) or to continue oral steroids in low doses (group B). Of the 113 patients enrolled, 65 were randomized to group A and 68 to group B. All patients were followed for 2 years. During the study 28 (43%) group A patients required reintroduced corticosteroids. One patient died, in group B. The Graft survival rate was 97% in group A and 90% in group B. There were more biopsy-proven rejections in group A (32% vs 16%; P = .044). The mean creatinine clearance was 54 +/- 21 mL/min in group A vs 56 +/- 22 mL/min in group B. Mean levels of serum cholesterol tended to be lower in group A, but the difference was of borderline significance (191 +/- 91 vs 251 +/- 188 mg/dL; P = .07). Vascular thrombosis (0 vs 5) and pneumonia requiring hospitalization (2 vs 7) tended to be more frequent in group B. Only three cases of CMV infection (1 vs 2) occurred. An immunosuppressive therapy with everolimus and low-dose CsA allows one to obtain excellent renal graft survival and stable graft function at 2 years. Early interruption of steroids in patients treated with this regimen may increase the risk of acute rejection, but neither affects graft survival nor graft function, while possibly reducing the risk of hyperlipemia and vascular thrombosis. About 60% of patients given everolimus and low-dose CsA can definitively stop steroids after 1 week.

Adolescent↗
PubMed2004

Effect of calcineurin inhibitors on extracellular matrix turnover in isolated human glomeruli.

INTRODUCTION: Although chronic cyclosporine toxicity is mainly characterized by tubular atrophy and interstitial fibrosis, glomerular injury with expansion of mesangial matrix and sclerosis is not uncommon. Tacrolimus is a newer calcineurin inhibitor that has been used in renal transplant recipients as primary or rescue therapy. Clinical trials suggest an improved long-term graft survival among patients treated with tacrolimus. Recently we have shown that tacrolimus and cyclosporine have similar effects on extracellular matrix turnover in cultured cells. The present study was performed to investigate the effects of the calcineurin inhibitors on whole glomeruli extracellular matrix turnover. METHODS: Human glomeruli isolated from kidney biopsies just before transplantation were incubated with culture media containing either cyclosporine (200 ng/mL) or tacrolimus (10 ng/mL) for 24 hours. Glomeruli incubated only with culture medium were used as control. RESULTS: The expressions of (alpha2)IV collagen, metalloprotease 9 (MMP9), tissue inhibitors of metalloproteases 2 (TIMP-2), and TGFbeta were evaluated by in situ reverse transcription and polymerase chain reactions (RT-PCR). beta-actin was used as a control gene. Cyclosporine (but not tacrolimus) increased the expression of (alpha2)IV collagen and TIMP2 in isolated glomeruli. TGF-beta was markedly increased by cyclosporine. MMP9 expression was not affected by the calcineurin inhibitors. By light microscopy kidney biopsies did not show pathologic changes. CONCLUSION: Cyclosporine treatment modulates extracellular matrix turnover in isolated human glomeruli, inducing an imbalance between synthesis and degradation. This effect, not observed in tacrolimus-treated human glomeruli, may induce the extracellular matrix deposition and sclerosis characteristic of chronic cyclosporine toxicity.

Biomarkers↗
PubMed2004

Platelet-Independent defect in hemostasis associated with sirolimus use.

Sirolimus is currently used to prevent rejection of solid organ transplant, and sirolimus-eluting stents have shown promise for the prevention of coronary artery restenosis. Thrombocytopenia is a well-known adverse effect of sirolimus limiting its use. Herein we report on a patient in whom sirolimus caused a platelet-independent hemostasis defect. The patient was a 52-year-old woman who underwent renal transplant with consequent normal kidney function. The immunosuppressive regimen included basiliximab, steroids, and cyclosporine induction later shifted to sirolimus and mycophenolate due to biopsy findings of tubular necrosis on day 6 posttransplantation. At discharge the serum creatinine was 0.7 mg/dL. Four months after transplantation the patient was admitted to our hospital because of fever (37.5 degrees C to 38 degrees C), anorexia, and asthenia. Blood analysis showed: creatinine 1.7 mg/dL, Hb 9.6 g/dL, WBC 6 x 10(3)/microL, PLT 123 x 10(3)/microL, liver function tests normal, LDH 720 mU/mL, fibrinogen 628 mg/dL, d-dimer 0.42 ng/mL, FDP > 40 ng/mL, INR 1.10, PT 87%, aPTT 40 seconds. Cultures and tests for infection were negative. Serum sirolimus level was 25.9 ng/mL. The following day the serum creatinine rose to 2.3 mg/dL and diuresis fell to 20 mL/h. Multiple bleeding times (Ivy test) performed before the renal biopsy were repeatedly over 30 minutes (normal 3 to 5 minutes), despite normal platelet count and platelet function studies. There was no spontaneous aggregation and in vitro aggregation was normal (collagen, ADP, adrenalin, and ristocetin induced). Coagulation studies showed a defect in fibrin formation and a reduction of fibrinolysis. Suspension of sirolimus treatment was followed by remission of fever, improvement of renal function (serum creatinine 1.2 mg/dL), and normalization of bleeding time.

Blood Platelets↗
PubMed2004

Hyperkalemia-induced ECG abnormalities in patients with reduced renal function.

Hyperkalemia is a potentially lethal condition to be aware of in the presence of ECG abnormalities especially in patients with reduced renal function. However, ECG abnormalities are not always dependent on the degree ofhyperkalemia but may be aggravated by the rapidity of the development of hyperkalemia and by associated electrolyte disorders. We describe 3 patients with renal failure and different ECG changes induced by hyperkalemia. More severe changes were observed when hyperkalemia developed rapidly, but not in presence of electrolyte disorders. Even minor ECG abnormalities must alarm physicians in patients with renal failure since severe hyperkalemia is not always associated with critical ECG changes.

Aged↗
PubMed2001

Hepatocyte growth factor/scatter factor released during peritonitis is active on mesothelial cells.

Peritonitis causes mesothelial detachment that may result in persistent peritoneal denudation and fibrosis. We investigated whether hepatocyte growth factor (HGF), a scatter factor that induces detachment from substrate and fibroblastic transformation of several cell types, is produced during peritonitis and is active on mesothelial cells. We studied 18 patients on peritoneal dialysis, 9 uncomplicated, 9 with peritonitis. HGF was measured in serum, peritoneal fluid, and supernatant of peripheral blood mononuclear cells and peritoneal mononuclear cells. Primary culture of human peritoneal mesothelial cells and the human mesothelial cell line MeT-5A were conditioned with recombinant HGF, serum, and peritoneal fluid. HGF levels were significantly higher in serum and peritoneal fluid of peritonitic than uncomplicated patients. Mononuclear cells of peritonitic patients produced more HGF than cells of uncomplicated patients. Recombinant HGF, serum, and peritoneal fluid of peritonitic patients caused mesothelial cell growth, detachment, transformation from epithelial to fibroblast-like shape, overexpression of vimentin, and synthesis of type I and III collagen. In conclusion, HGF released during peritonitis causes a change in mesothelial cell phenotype and function. HGF may affect the healing process facilitating repair through mesothelial cell growth, but may contribute to peritoneal fibrosis inducing cell detachment with mesothelial denudation and collagen synthesis.

Ascitic Fluid↗
PubMed2001

Long-term exposure to high glucose up-regulates VCAM-induced endothelial cell adhesiveness to PBMC.

BACKGROUND: The changes induced on endothelial cells by a long-term exposure to high glucose, a situation that mimics the hyperglycemia of diabetics, have not yet been determined. We compared short- and long-term effects of elevated glucose on macrovascular and microvascular endothelial cells. METHODS: Endothelial cells were grown in high-glucose media for 24 hours and for 8 weeks. Cell proliferation was evaluated by cell counting, apoptosis and expression of adhesion molecules by flow cytometry; nitric oxide (NO) by measuring the concentration of nitrite/nitrate in the cell supernatant; alpha 2(IV) collagen mRNA and protein by reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The adhesion of peripheral blood mononuclear cells (PBMCs) to endothelial cells was evaluated by adhesion assay. In some experiments, endothelial cells were preincubated with anti-vascular cell adhesion molecule-1 (VCAM-1) and anti-receptor for advanced glycation end product (RAGE) blocking antibodies. RESULTS: At 24 hours, but not at 8 weeks, high glucose increased endothelial cell proliferation and apoptosis. High glucose did not modify NO synthesis at 24 hours and 8 weeks. Collagen production and expression were increased only after eight weeks. VCAM-1 but not intercellular adhesion molecule-1 was up-regulated after 8 weeks, a change not observed after 24 hours. The adhesion of PBMCs was significantly increased at eight weeks and was completely abrogated by anti--VCAM-1 and by anti-RAGE antibodies. After 24 hours, there was a modest increase of PBMC adhesion that was not blunted by anti-RAGE antibodies. CONCLUSIONS: Increased adhesion of PBMCs, caused by up-regulation of VCAM-1 with a mechanism involving advanced glycation end product (AGE) adducts, and augmented collagen deposition are critical effects of long-term high glucose on endothelial cells, and may eventually promote the atherosclerotic process.

Animals↗
PubMed2001

Polarization of T-helper lymphocytes toward the Th2 phenotype in uremic patients.

T-helper (Th) lymphocytes consist of Th1 and Th2 subsets. Th1 cells are effectors of cell-mediated immunity and secrete interferon-gamma (IFN-gamma), which recruits new Th1 cells in cooperation with interleukin-12 (IL-12; produced by monocytes) and inhibits Th2 differentiation. Th2 cells produce IL-4 and IL-10, which inhibit IFN-gamma secretion and cell immunity. We investigated whether the impaired immune response in uremia is associated with an altered balance of Th1/Th2. Peripheral-blood mononuclear cells (PBMCs) were collected from patients with chronic renal failure (CRF) on conservative treatment (CRF patients), patients with end-stage renal disease (ESRD) on regular hemodialysis therapy (ESRD-HD patients), and healthy controls (CON). CD4(+) cells were isolated from PBMCs by negative selection using a magnetic labeling system. PBMCs and purified CD4(+) cells were cultured in Iscove's medium and Iscove's medium plus mitogens (phytohemagglutinin and lipopolysaccharide). IFN-gamma, IL-12, IL-4, and IL-10 were measured in supernatant. The constitutive release of IL-4 and IL-10 by PBMCs and CD4(+) cells of CRF and ESRD-HD patients was increased by five to eight times in comparison with CON (P < 0.001). Constitutive IFN-gamma release by PBMCs of ESRD-HD patients was undetectable, although they secreted an increased amount of IL-12. Mitogen-stimulated release of IFN-gamma by PBMCs and CD4(+) cells of CRF and ESRD-HD patients was blunted (average PBMCs: CON, 115.8 pg/2 x10(6) cells; CRF, 81.8 pg/2 x10(6) cells; ESRD-HD, 9.3 pg/2 x10(6) cells; CD4(+) cells: CON, 358.0 pg/5 x 10(5) cells; CRF, 165.4 pg/5 x 10(5) cells; ESRD-HD, 43.5 pg/5 x 10(5) cells). The ability of PBMCs of ESRD-HD patients to secrete IFN-gamma was recovered after IL-4 and IL-10 neutralization. Uremia is associated with a prevalence of Th1 over Th2 cells and a configuration of cytokine network that depresses cell-mediated immunity.

CD4-Positive T-Lymphocytes↗
PubMed2000

Cyclosporine induces different responses in human epithelial, endothelial and fibroblast cell cultures.

BACKGROUND: Nephrotoxicity, accelerated atherosclerosis, and graft vascular disease are common complications of cyclosporine long-term treatment characterized by a wide disruption of organ architecture with increased interstitial areas and accumulation of extracellular matrix (ECM). How cyclosporine induces these changes is not clear, but it is conceivable that they are the sum of changes induced at the cell level. METHODS: We studied the effects of cyclosporine on human endothelial (HEC), epithelial (HK-2), and fibroblast (MRC5) cells. Cell proliferation was evaluated by cell counting, apoptosis and collagen production by enzyme-linked immunosorbent assay, and nitric oxide by measuring the concentration of nitrite/nitrate in the cell supernatant. (alpha1)I and (alpha2)IV collagen, matrix metalloprotease-9 (MMP9), and tissue inhibitors of metalloprotease-1 (TIMP-1) mRNA levels were measured by reverse transcription-polymerase chain reaction. Proteolytic activity was evaluated by zymography. RESULTS: Cyclosporine showed a marked antiproliferative and proapoptotic effect on endothelial and epithelial cells. Fibroblast growth was not affected by cyclosporine. Nitric oxide was up-regulated by cyclosporine in epithelial cells and fibroblasts but not in endothelial cells. (alpha1)I and (alpha2)IV collagen synthesis was increased in cyclosporine-treated endothelial and epithelial cells, respectively. Proteolytic activity was increased in endothelial and epithelial cells. TIMP-1 mRNA was up-regulated by cyclosporine in fibroblasts. CONCLUSIONS: Our results demonstrate that cyclosporine exhibits an antiproliferative effect on endothelial and epithelial cells. This effect is associated with induction of apoptosis probably via nitric oxide up-regulation in epithelial cell cultures. Cyclosporine treatment induces ECM accumulation by increasing collagen synthesis in endothelial and epithelial cells and reducing its degradation by up-regulating TIMP-1 expression in fibroblasts. We conclude that cyclosporine affects cell types differently and that the disruption of organ architecture is the result of multiple effects at the cell level.

Actins↗
PubMed2000

Risk factors for chronic renal dysfunction in cardiac allograft recipients.

Renal dysfunction is one of the most common and threatening complications in heart transplant recipients. Even if ciclosporin seems to play a central role in inducing renal damage, other factors may concur or predispose to renal injury. In order to identify factors responsible for renal dysfunction, we retrospectively studied a cohort of 114 cardiac transplant recipients during a follow-up period of at least 3 years. The patients had a normal renal function before and 0.5 months after heart transplantation. Doubling of baseline serum creatinine or attainment of serum creatinine steadily above 176.8 micromol/l (2.0 mg/dl) was used as criterion to define the end-point renal dysfunction. A series of clinical and laboratory variables were obtained from the patients' charts at different time intervals, and their prognostic value for the occurrence of renal dysfunction was calculated by Cox proportional hazards models. 23 out of 114 patients reached the end point after a median time period of 21 months. High serum triglyceride, alanine aminotransferase, alkaline phosphatase, ciclosporin, urea, glucose, and hemoglobin levels were shown to be associated with the development of renal dysfunction. Four variables, i.e., triglyceride, ciclosporin, urea, and alkaline phosphatase, had an independent prognostic value. Our results confirm a role for ciclosporin in inducing renal dysfunction and identify hyperlipidemia and an increased plasma urea level as risk factors for renal dysfunction in heart transplant recipients.

Adolescent↗
PubMed1999

Hemodialysis prevents liver disease caused by hepatitis C virus: role of hepatocyte growth factor.

UNLABELLED: Hemodialysis prevents liver disease caused by hepatitis C virus: Role of hepatocyte growth factor. BACKGROUND: Hemodialysis increases markedly the serum levels of hepatocyte growth factor (HGF) so that regular dialysis treatment (RDT) mimics the regular administration of HGF as a drug. Therefore, we have studied the effects of dialysis-associated HGF production on the severity of liver damage caused by hepatitis C virus (HCV). METHODS: Biochemical tests of liver function and liver biopsy were performed in 10 patients on RDT and in 11 patients without renal disease (WRD) converted to anti-HCV serum-positive test for the same time (48 +/- 4 months). The HGF serum concentration was measured by enzyme immunoassay. In patients on RDT, HGF was measured just before starting a dialysis session (T0), at 15 and 240 minutes of dialysis (T15 and T240), and 24 hours later (T24 hr). RESULTS: Serum HGF was similar in WRD (average 0.17 ng/ml) as in RDT at T0 (0.25 ng/ml). In RDT serum HGF increased markedly at T15 and T240 (5.51 and 2.67 ng/ml, respectively, P < 0. 001 vs. WRD and T0) and was still higher than baseline at T24 hr (0. 41 ng/ml, P < 0.05). Both grade of necroinflammatory activity and stage of fibrosis were significantly lower in RDT than in WRD (both, P < 0.001). The number of apoptotic hepatocytes was also significantly reduced in patients on RDT compared with patients WRD. CONCLUSION: These results show that HCV-related liver disease is more benign in patients on RDT. The phenomenon may depend on the marked and prolonged HGF release caused by dialysis.

Acute Disease↗
PubMed1998

Hemodialysis stimulates hepatocyte growth factor release.

Studies were performed in 26 patients on regular dialysis treatment with cuprophane (CU), polymethylmetacrilate (PMMA) or cuprammonium (CAM) dialyzers. Controls were six patients with chronic renal failure but not on regular dialysis treatment (CRF) and six healthy subjects (N). Blood was collected at the start (T0), and at 15 (T15) and 240 (T240) minutes of dialysis to measure the serum hepatocyte growth factor (HGF) concentration and to study HGF production by peripheral blood mononuclear cells (PBMC) in vitro. The form of HGF (that is, inactive/monomeric, active/dimeric) present in the serum was analyzed by immunoblotting. In addition, the ability of serum to stimulate proliferation of tubular cells (HK-2) and HGF release by PBMC and fibroblasts (MRC-5) was investigated. At T0, serum HGF levels were identical to that of the controls. In patients treated with CU, serum HGF rose from 0.24 ng/ml at T0 to 7.44 ng/ml at T15, and remained high at T240. PBMC collected at T15 and T240 released significantly more HGF in vitro than those collected at T0. Serum at T15 stimulated proliferation of HK-2 cells and the release of HGF by PBMC and MRC-5 cells. The PMMA and CAM dialyzers had similar effects as the CU. These results indicate that dialysis induces a striking rise in serum HGF and a prompt circulation of factor(s) stimulating HGF release. Dialysis-activated PBMC release HGF.

Case-Control Studies↗
PubMed1998

Stimulation of hepatocyte growth factor in human acute renal failure.

Hepatocyte growth factor (HGF) is a potent mitogen for tubular cells. Experimental injury to the kidney is associated with HGF release both locally and by distant organs stimulated by circulating 'injurins'. In this study, the serum HGF concentration was measured in patients with acute renal failure (ARF). Normal subjects and chronic renal failure patients either not on dialysis or on regular dialysis treatment served as controls. Human mesangial cells were incubated with sera from ARF patients and controls. The serum HGF concentration was strikingly increased in ARF patients (478 +/- 68 ng/dl) and was normal in chronic renal failure patients not on dialysis (20 +/- 3 ng/dl) and in those on regular dialysis treatment (25 +/- 3 ng/dl). Serum of ARF patients strongly stimulated HGF release from mesangial cells (1,384 +/- 55 ng/ml) in comparison with normal serum (67 +/- 10 ng/ml). These results indicate that in ARF HGF participates in tubular repair both as an endocrine factor, released in the circulation, and as a paracrine substance, diffusing to the tubules from the mesangium.

Acute Kidney Injury↗
PubMed1997

The famous case of rheumatic hematuria described by Giammatteo Ferrari da Grado, professor at the University of Pavia (1432-1472).

Giammatteo Ferrari da Grado was an influential professor and teacher of medicine at the University of Pavia in middle of the 15th century. He authored three important texts, among which is the Consilia, a collection of cases he visited and/or consulted. Among these, Ferrari describes a case of rheumatic hematuria in an eminent patient, Gaston de Foix, prince of Navarre. Following a precise description of the symptoms, he makes a complex pathogenic interpretation based on the theory of humors current at the time, and goes on to offer his patient a generous spectrum of herbal, hygienic and dietetic remedies.

Education, Medical↗
PubMed1997

Circulating serum lectins of patients with IgA nephropathy stimulate IL-6 release from mesangial cells.

Previously, the authors reported that the serum of patients with immunoglobulin (Ig) A nephropathy stimulated peripheral leukocytes, and this effect was inhibited by nominal haptens for lectins. In vitro studies have shown that lectins can bind to rat mesangial cells and cause their activation. This study was performed to investigate whether the serum of IgA nephropathy patients contains lectins that activate mesangial cells, i.e., induce release of interleukin (IL)-6, a nephritogenic cytokine. The serum of patients was adsorbed by affinity chromatography on resins loaded with lectin-binding sugars. After adsorption, serum supernatant was collected and the resins were then eluted. Human mesangial cells were conditioned with native serum, post-adsorption supernatant, and eluate (all three at 10%) for 24 h, and the release of IL-6 was determined by ELISA. Normal serum was used as control. Incubation of mesangial cells with IgA nephropathy patients serum raised average IL-6 release from 8.5 pg/mL to 274.1 pg/mL. Adsorption in beta-D-glucose and N-acetyl-D-glucosamine caused a fall in the activity of patients' serum, to 17.0 and 63.7 pg/mL, respectively, and the activity lost was recovered in the eluate (185.2 and 142.7 pg/mL, respectively). Neither adsorption on N-acetyl-D-galactosamine nor on fucosylamine was associated with any effect on serum activity; accordingly, no activity was found in the eluates. Serum of patients with non-IgA mesangiocapillary nephritis did not stimulate mesangial cells. These results show that the serum of IgA nephropathy patients contains specific lectins that stimulate IL-6 nephropathy by mesangial cells and are, therefore, potential nephritogenic.

Adult↗