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Biomedical subjects

G Pertosa

Publications and source records attributed to G Pertosa.

At least 19 recordsLinked to original sources
PubMed2000

Clinical relevance of cytokine production in hemodialysis.

Blood-dialyzer interaction in hemodialysis has the potential to activate mononuclear cells leading to the production of inflammatory cytokines. The extent of activation is dependent on the dialyzer material used and is considered an index of biocompatibility. Cytokines, such as interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and IL-6, may induce an inflammatory state and are believed to play a significant role in dialysis-related morbidity. The interleukin hypothesis suggests that the release of proinflammatory cytokines acts as an underlying pathophysiologic event in hemodialysis-related acute manifestations, such as fever and hypotension. Nevertheless, a cytokine overproduction may alter sleep pattern in chronic hemodialyzed patients, thus explaining the presence of sleep disorders in these patients. A potential role of cytokines in chronic-related morbidity has also been suggested. High levels of some inflammatory cytokines are often associated with anemia caused by hyporesponsiveness to erythropoietin. Cytokine production may also play a relevant role in bone remodeling by regulating osteoblast/osteoclast cell functions and parathyroid hormone (PTH). Finally, cytokine release may have a long-term deleterious effect on mortality of uremic patients by altering immune response and increasing susceptibility to infections. Bioincompatibility of dialytic membranes may also contribute to malnutrition in dialysis patients by increasing the monocyte release of catabolic cytokines such as TNF-alpha and IL-6. Bioincompatible dialytic treatment may induce an inappropriate monocyte activation and cytokine production, which, in turn, may mediate some of the immune and metabolic dysfunction associated with hemodialysis. The use of biocompatible dialytic membranes appears to reduce the monocyte activation and to improve the survival of hemodialysis patients.

Biocompatible Materials↗
PubMed1998

Interleukin-6, interleukin-8 and monocyte chemotactic peptide-1 gene expression and protein synthesis are independently modulated by hemodialysis membranes.

BACKGROUND: Uremia produces a wide range of abnormalities of the immune system. Blood-membrane interaction in hemodialysis results in activation and severe dysfunction of peripheral blood mononuclear cells (PBMC). However, the question of whether the use of different dialytic membranes may improve PBMC dysfunctions remains unanswered. METHODS: To address this issue, the spontaneous interleukin (IL)-6, IL-8 and monocyte chemotactic peptide-1 (MCP-1) gene expression and protein release were studied in PBMC isolated from 7 healthy subjects, 8 uremic patients on conservative therapy and 8 uremic patients undergoing subsequent one month periods of hemodialysis with cuprophan (CU) and high-flux noncomplement activating membranes, polymethylmethacrylate (PMMA) and polyamide (PA). At the end of each period of treatment, PBMC were harvested at the beginning (T0) and after 180 minutes of dialysis (T180), and then were cultured in complete medium. IL-6, IL-8 and MCP-1 mRNA expression were studied by RT-PCR. In addition, MCP-1 gene expression was evaluated also by in situ hybridization. Cytokines released in the supernatant were measured by ELISA. RESULTS: Compared to the control group, PBMC from uremic patients on conservative therapy and treated by CU showed a clear reduction in the cytokine release, while PMMA and PA membranes were able to normalize IL-6, IL-8 and MCP-1 protein concentration, which had been reduced by CU treatment. Interestingly, at T0, mRNA expression for all three cytokines was increased in the patients treated by CU, when compared to the control group and the uremic patients on conservative therapy. A further up-regulation was observed at T180. PMMA and PA treatment, despite increasing the cytokine secretion, significantly reduced the dialysis-induced cytokine gene expression. CONCLUSION: PBMC exposure to CU membranes results in cytokine mRNA overexpression associated with a paradoxically reduced protein release. In contrast, long-term hemodialysis with synthetic high-flux membranes reduces IL-6, IL-8 and MCP-1 gene expression and improves the ability of PBMC to secrete these cytokines. The reduced cytokine secretion during bioincompatible dialysis may reflect a PBMC adaptation that protects uremic patients against the inflammatory effects of persistent cytokine release.

Adult↗
PubMed1998

[DRG's and cost/efficacy indicators in nephrology and dialysis. Results at a hospital division].

The Diagnosis Related Groups (DRGs) classification system correlates hospital performance with their relative costs and encourages more efficient productive processes. We report the following parameters: a) the distribution of hospital discharges according to the Major Diagnostic Categories (MDCs) and DRGs; b) the relationship between mean length of stay and threshold values; c) economic analysis of the cost-reimbursement pay-off. The results showed that 71.3% of DRGs belonged to nephro-urological MDC 11 and 28.7% in other internal MDCs (mainly involving cardiac and respiratory system). Of the latter, 67.7% were utilized for dialysis and transplant patients and kidney donors. In MDC 11 the most common DRGs were: the surgical DRG 315, produced by the vascular accesses for hemodialysis and by insertion of Tenckoff catheter for peritoneal dialysis, DRG 316 by cases of acute and chronic renal failure, DRG 332 by biopsy-proven glomerulonephritides. The length of stay was most commonly within range of one-third of threshold value for specific DRG; there was a low percentage of one-day stays and outlier cases. The economic analysis demonstrated that mean daily reimbursement sum was 590,714 ITL. Analysis of the overall costs yielded a mean daily cost of 455,838 ITL. In conclusion, quality indicators show that, appropriately, our specialist activity is largely devoted to the diagnosis and treatment of acute and chronic nephropathies and complications following dialysis and renal transplant.

Adolescent↗
PubMed1995

Endotoxins modulate chronically tumour necrosis factor alpha and interleukin 6 release by uraemic monocytes.

We examined in vivo the release of tumour necrosis factor alpha (TNF alpha) and interleukin 6 (IL-6) by uraemic monocytes upon stimulation with endotoxin-contaminated bicarbonate concentrate. Twelve uraemic patients underwent 1-month-subsequent periods of standard haemodialysis (SHD) with cuprophane (CU), a high-complement-activating membrane (6 patients), or haemodiafiltration (HDF) with polyacrylonitrile (PAN), a low-complement-activating membrane (6 patients), by using a dialysate prepared with either non-sterile bicarbonate concentrate tanks (phase 1) or sterile bicarbonate concentrate bags (phase 2). TNF alpha and IL-6 concentrations were determined in monocyte supernatants by ELISA; endotoxin levels in bicarbonate concentrates were measured by a chromogenic limulus amoebocyte lysate (LAL) assay. A significant increase in LAL reactivity was found in bicarbonate concentrate tanks compared to sterile bags (P < 0.001). Non-sterile dialysate caused a significant (P < 0.001) predialytic increase in monocyte TNF alpha release as compared to controls and non-dialysed uraemic patients. One month treatment with sterile bicarbonate significantly decreased TNF alpha predialytic activity in monocyte supernatants (P < 0.001) to levels closer to those of non-dialysed uraemic patients. A similar decrease was observed for IL-6 production. Dialytic treatment induced a further increase in both TNF alpha and IL-6 production, particularly in phase 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

C5b-9 generation and cytokine production in hemodialyzed patients.

The role of the complement system in the induction of cytokine release is controversial. Plasma terminal C complex C5b-9 along with Bb and C4d fragments were evaluated in 22 patients during routine acetate or bicarbonate hemodialysis using cuprophane membranes and hemodiafiltration (HDF) or acetate-free-biofiltration (AFB) using polyacrylonitrile (PAN) membranes. In a subgroup of six uremic patients we also evaluated the release of tumor necrosis factor (TNF alpha) and interleukin-6 (IL-6) from monocytes before and after six subsequent sessions with bicarbonate-cuprophane, HDF and AFB-PAN. At beginning of the dialysis increased plasma C5b-9 levels were found in patients treated by acetate or bicarbonate-cuprophane. Moreover, a rapid significant (P < 0.001) increase of C5b-9 levels occurred in both groups 15 minutes after the onset of the hemodialysis procedure with a plateau at 180 minutes. In contrast, only a slight increase in the plasma C5b-9 levels was observed in patients dialysed with HDF or AFB using PAN membranes. This increase was more pronounced with HDF at 0 minutes compared with controls. A positive linear correlation was found in all patients between C5b-9 generation and plasma Bb levels at different times in the dialysis session. The production of C4d fragment remained unchanged in all groups, indicating that C5b-9 complex generation is due to the prevalent alternative complement pathway activation. The pattern of cytokine production strictly resembled the complement system activation and C5b-9 generation.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Involvement of peripheral blood monocytes in haemodialysis: in vivo induction of tumour necrosis factor alpha, interleukin 6 and beta 2-microglobulin.

Our aim was to evaluate the role of three different variables in the activation of the monocyte system: dialysis membrane (cuprophane or polyacrylonitrile), dialysate (acetate or bicarbonate), and procedure (standard or high-flux haemodialysis). By ELISA test we measured the 'in vivo' intracellular (monocyte-associated) production and extracellular release of tumour necrosis factor alpha (TNF alpha), interleukin-6 (Il-6) and beta 2-microglobulin (beta 2-M) by monocytes from 20 uraemic patients before and after the dialysis session. At the beginning of the dialysis session, uraemic patients' cultured monocytes spontaneously released a greater amount of TNF alpha, Il-6 and beta 2-M compared to normal controls. However, no differences in cytokine and beta 2-M were observed in monocyte lysate between the two groups. At the end of the dialysis session, cultured monocytes from patients treated with cellulosic membranes and acetate dialysate showed greater TNF alpha values than normal controls (P less than 0.001 and P less than 0.05 respectively). Moreover, TNF alpha and Il-6 values were strictly correlated (P less than 0.05). These results clearly show an activation of the monocyte system in uraemic patients undergoing periodic haemodialysis. The implicated factors may be multiple, such as complement activating cellulosic membranes or acetate dialysate. The production of TNF alpha, Il-6 and beta 2-M may explain some of the pathological findings observed in long-term haemodialysis patients.

Adult↗
PubMed1989

Effect of fibronectin on C3b and Fc receptor-mediated phagocytosis by peripheral blood monocytes in uraemic patients.

The influence of human fibronectin was evaluated on the phagocytosis in vitro of C. albicans (C3b receptor-mediated) and IgG antibody-coated sheep erythrocytes (Fc receptor-mediated) by the peripheral blood monocytes of 40 uraemic patients undergoing periodic haemodialysis. Some nutritional parameters (albumin, transferrin, C4, C3, haematocrit, lymphocyte count, height and bodyweight) were also evaluated. Results showed significantly decreased plasma fibronectin (P less than 0.001) and reduced C3b receptor (R)- and FcR-mediated phagocytosis in uraemic patients (P less than 0.001). A strict correlation was found between fibronectin and C3bR-mediated phagocytosis (P less than 0.001) and between fibronectin and FcR-mediated phagocytosis (P less than 0.05). In 20 patients with decreased fibronectin concentrations and reduced phagocytic function, the in vitro incubation of peripheral blood monocytes with 50 micrograms/ml of purified fibronectin significantly enhanced C3bR-(P less than 0.001) but not FcR-mediated phagocytosis. Study of nutritional parameters in the uraemic patients revealed that values of fibronectin, C3, IgG and albumin were significantly reduced. Fibronectin correlated significantly (P less than 0.001) with C3. A good relationship (P less than 0.05) was also found between the plasma fibronectin and bodyweight loss. A greater incidence of infectious disease was observed in patients with decreased plasma fibronectin than in uraemic patients with normal values (P less than 0.05). The results suggest that a decrease in plasma fibronectin in uraemic patients could impair the peripheral blood monocyte phagocytic capacity and be potentially dangerous, predisposing the patient to infections. The determination of fibronectin concentration in these patients may, therefore, have a potential value as an indicator of peripheral blood monocyte phagocytic function.

Adult↗
PubMed1989

Influence of different dialyzer membranes on plasma fibronectin levels in hemodialyzed patients.

Plasma fibronectin (FN) was assayed in 30 patients with chronic renal failure under conservative therapy, 60 uremic patients undergoing periodic hemodialysis, and 7 patients treated by hemofiltration. Plasma FN was significantly lower in uremic patients on conservative therapy and in those who received intermittent hemodialysis than in the control group. No difference was seen between mean FN concentrations using different dialyzer membranes. Nevertheless, plasma FN levels were significantly higher in subjects after intermittent hemofiltration. There was no evidence of activation of the coagulation system or of any correlation between FN and fibrinogen values. These findings suggest that conventional hemodialysis is not effective in improving the low levels of plasma FN found in uremic patients, whereas intermittent hemofiltration raises FN. These differences may be due to the fact that during hemofiltration, even when using the same dialyzer membranes as in conventional hemodialysis, some "substances" with high molecular weight that could block the synthesis of FN could be removed.

Adult↗
PubMed1986

Serum profiles of the regulatory complement proteins during the progression of renal damage in human glomerulonephritis.

Persistent activation of the complement system after escape from control by the regulatory proteins results in an excessive release of split products with inflammatory properties. Serum levels of the regulatory proteins of the complement system (Cl-INH, H, I and AT III) were assayed by the radial immunodiffusion technique in 521 serum samples from 124 patients with idiopathic chronic glomerulonephritis divided into two groups: 81 cases with normal renal function (NRF), and 43 cases with deteriorated renal function (DRF). Significant high mean levels of Cl-INH, H, I and AT III were found in patients with NRF, when they were compared with DRF patient groups. Positive correlations between the regulatory proteins and the corresponding complement components were found in patients with NRF, whereas they were reduced considerably in patients with DRF. Serial measurement of the control proteins showed a decay of the levels of Cl-INH, H and I in patients with progressive impairment of renal function. The presence of high levels of regulatory proteins suggest that a control mechanism may occur in patients with NRF; measurement of these proteins could, therefore, be of prognostic value, as the presence of high levels are indicative of a block of the complement system.

Antithrombin III↗
PubMed1986

Plasma fibronectin levels in patients with chronic uremia.

Plasma fibronectin (FN) concentration was measured in patients with idiopathic glomerulonephritis (GN) with or without impaired renal function, in uremic patients undergoing periodic hemodialysis and in renal transplant patients before and after an acute rejection crisis. Results show normal FN levels in idiopathic GN and in renal transplant patients with normal renal function, while significantly lower levels were found in GN with severe renal damage, in uremia before and after dialysis, and in renal transplant patients during acute and chronic graft rejection. Significant correlations between high serum creatinine values and low plasma FN levels were found in renal transplant patients. These findings suggest that the kidney may influence FN levels in the blood since acute (rejection crisis) and chronic renal failure (uremia) cause low concentrations of this protein, while levels tend to return to normal values in patients with uremia after renal transplantation. We hypothesize that the normal kidney removes or perhaps degrades some substances or hormones that may control the release or synthesis of FN. These substances are not dialyzed by cellophane membranes since low plasma FN levels persist after periodic hemodialysis. Only the renal graft provokes an increase of FN in the blood stream.

Adult↗
PubMed1983

Circulating immune complexes in infected ventriculoatrial and ventriculoperitoneal shunts.

Distinguishing infected from noninfected ventriculoatrial (VA) or ventriculoperitoneal (VP) shunts is prognostically and therapeutically important. Eighty-seven serum samples from twenty-seven patients with VA or VP shunts were studied for the presence and quantification of circulating immune complexes. Eighty-three percent of the samples from infected shunts presented circulating immune complexes. Mean values of immune complexes in patients with infected shunts were significantly higher than in those without infection. In febrile, septicemic patients with few clinical symptoms, immune complexes were present, and their measurement in serial serum samples was a significant diagnostic aid. If circulating immune complex levels are not detectable, a shunt infection is less likely to be present.

Adult↗
PubMed1982

Biological significance of the C3 nephritic factor in membranoproliferative glomerulonephritis.

Serum levels of the C3 nephritic factor (C3NeF), an IgG autoantibody directed against the C3bBb convertase of the alternative complement pathway, and of eight complement components (C1q, C4, C3, C3d, C5, C9, fB and properdin) were measured in 109 serum samples from 27 patients with idiopathic membranoproliferative glomerulonephritis (MPGN) (type I, 20 cases, and type II, 7 cases) and 14 patients with secondary MPGN. Correlations between the concentrations of C3NeF, serum complement levels and progression of the renal damage were studied during the course of the disease in 14 patients with C3NeF activity. The results showed that (1) C3NeF activity was more frequent in patients with type II MPGN than in patients with type I disease; nevertheless there was a high incidence of this splitting activity in patients with secondary MPGN, (2) high levels of the complement components were present in patients with MPGN, (3) low levels of C3 occurred frequently in type II disease and in secondary MPGN, (4) there was no correlation between C3, fB and C3NeF levels, (5) the presence of C3NeF was associated with a more rapid deterioration of renal function. Longitudinal studies showed that serum levels of C3NeF were not satisfactory for monitoring the clinical course of the illness and, in this respect, are similar to the levels of other autoantibodies in patients with autoimmune disease. As MPGN is a clinical syndrome with various pathogeneses, we suggest that the autoantibody, C3NeF, should be considered only as a marker of some forms of MPGN.

Autoantibodies↗
PubMed1981

Activation of the alternative complement pathway by unidentified substances in human glomerulonephritis.

Activation of the alternative complement pathway (AP) has been investigated in 79 serial serum samples obtained from 28 patients which had different types of glomerulonephritis. Serum factors activating the AP of the complement system have been detected in 12 patients with various forms of glomerulonephritis. Immune complexes (IC), levels of complement components of the classical and the alternative pathways and cobra venom factor activity were measured. Serum specimens were subcategorized as 2 study populations: (i) patients with serum factors activating AP and (ii) patients with both serum activators and IC. Although CoVF-AH50, properdin factor B and C3 concentrations were comparably depressed in these two groups, the levels of Clq and C4 were very low only in patients with circulating IC. These data were highly suggestive of AP activation due to serum factor. In contrast the patients also showing circulating IC had activation of both pathways. The presence of these factors suggests that renal damage can be determined by other immunological stimuli.

Antigen-Antibody Complex↗