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Ciro Tetta

Publications and source records attributed to Ciro Tetta.

At least 19 recordsLinked to original sources
PubMed2006

Isolation and characterization of a stem cell population from adult human liver.

Several studies suggested the presence of stem cells in the adult normal human liver; however, a population with stem cell properties has not yet been isolated. The purpose of the present study was to identify and characterize progenitor cells in normal adult human liver. By stringent conditions of liver cell cultures, we isolated and characterized a population of human liver stem cells (HLSCs). HLSCs expressed the mesenchymal stem cell markers CD29, CD73, CD44, and CD90 but not the hematopoietic stem cell markers CD34, CD45, CD117, and CD133. HLSCs were also positive for vimentin and nestin, a stem cell marker. The absence of staining for cytokeratin-19, CD117, and CD34 indicated that HLSCs were not oval stem cells. In addition, HLSCs expressed albumin, alpha-fetoprotein, and in a small percentage of cells, cytokeratin-8 and cytokeratin-18, indicating a partial commitment to hepatic cells. HLSCs differentiated in mature hepatocytes when cultured in the presence of hepatocyte growth factor and fibroblast growth factor 4, as indicated by the expression of functional cytochrome P450, albumin, and urea production. Under this condition, HLSCs downregulated alpha-fetoprotein and expressed cytokeratin-8 and cytokeratin-18. HLSCs were also able to undergo osteogenic and endothelial differentiation when cultured in the appropriated differentiation media, but they did not undergo lipogenic differentiation. Moreover, HLSCs differentiated in insulin-producing islet-like structures. In vivo, HLSCs contributed to regeneration of the liver parenchyma in severe-combined immunodeficient mice. In conclusion, we here identified a pluripotent progenitor population in adult human liver that could provide a basis for cell therapy strategies.

Adipogenesis↗
PubMed2006

On-line hemodiafiltration reduces the proinflammatory CD14+CD16+ monocyte-derived dendritic cells: A prospective, crossover study.

It is not known whether high convective transport may have a role in modulating the chronic inflammation of hemodialysis (HD) patients. The aim of this study was to evaluate the effect of on-line hemodiafiltration (OL-HDF) on proinflammatory peripheral monocytes: Percentage of CD14+CD16+ cells and their telomere length and spontaneous or bacterial DNA-induced production of cytokines (TNF-alpha and IL-6). In a prospective, crossover study, 31 patients who were on high-flux HD (HF-HD) were evaluated. Patients underwent the following sequence of treatments (4 mo each): HF-HD (basal), OL-HDF (period 1), HF-HD (period 2), OL-HDF (period 3), and HF-HD (period 4). The dialysis characteristics were similar in the two modalities; the only difference was a higher convective transport in the OL-HDF than in the HF-HD. All patients who were on OL-HDF periods showed a significantly lower number of CD14+CD16+ cells than on HF-HD (18.5 +/- 2.3 basal versus 13.6 +/- 2.9 period 1 and 13.9 +/- 2.3 period 3; P = 0.001). By contrast, HF-HD restored the number of CD14+CD16+ cells to the basal values (19.2 +/- 2.8 and 18.6 +/- 1.4, periods 2 and 4, respectively; NS). During OL-HDF periods, the reduction of CD14+CD16+ was paralleled by a decreased number of short telomere cells. Spontaneous or bacterial DNA-induced production of cytokines (TNF-alpha and IL-6) was increased in HF-HD as compared with OL-HDF. In conclusion, these results demonstrate that as compared with HF-HD, OL-HDF markedly reduces the number of proinflammatory CD14+CD16+ cells and the production of TNF-alpha and IL-6. Future studies are needed to assess the possible therapeutic effect of convective transport on chronic inflammation that is associated with HD.

Adult↗
PubMed2006

Residual renal function and dialysis modality: is it really beneficial to preserve residual renal function in dialysis patients?

Residual renal function (RRF) contributes to the achievement of treatment adequacy in stage 5 chronic kidney disease (CKD-5) patients. It may facilitate patients' acceptance of renal replacement therapy (RRT) in allowing reduction of treatment time duration and minimising dietary and fluid restriction. It has been confirmed to improve dialysis patient outcomes. Attempts to preserve RRF in incident Stage 5 chronic kidney disease patients are still subject to intense controversies in the nephrology community. The aim of this review is to analyse the role of renal replacement modalities in the maintenance of RRF in dialysis patients. Under the scope of this manuscript, four questions are explored: Is the preservation of residual renal function an objective for dialysis adequacy? Does dialysis modality affect the decline of RRF? What are the factors implicated by this loss of RRF? At what expense can the maintenance of RRF be achieved in dialysis patients? Preservation of RRF is undoubtedly an interesting means to enhance the efficacy of renal replacement therapy and reduce dietary fluid restriction but it should not be considered as a goal of dialysis adequacy in dialysis patients. Further, preservation of RRF must be considered as a permanent trade-off between patient comfort and chronic fluid volume overload.

Chronic Disease↗
PubMed2006

Microinflammation in hemodialysis is related to a preactivated subset of monocytes.

Increased percentage of monocytes with low CD14 expression and that co-express CD16 (CD14+/CD16+) have been reported in hemodialysis (HD) patients. We sought to determine whether CD14+/CD16+ monocytes in HD therapy are sensibilized cells to a proinflammatory activity. Cells from 32 HD patients, and from 9 Systemic Lupus Erythematosus (SLE), 9 individuals with human immunodeficiency virus (HIV)-1- and 15 healthy controls were studied. Cells were analyzed by means of flow cytometry for CD14/CD16 expression and immune function (cytokine, chemokines, and sialoadhesin expression), and phagocytosis. Increased percentage of CD14+/CD16+ monocytes was observed in HD patients. Compared with CD14++ monocytes, the CD14+/CD16+ monocytes exhibited increased expression of proinflammatory cytokines and markers of differentiated cells. In addition, these monocytes showed an increased phagocytic activity. Similarly, CD14+/CD16+ monocytes from SLE and HIV patients showed increased inflammatory activity as compared with CD14++ cells. These results support that CD14+/CD16+ monocytes from HD patients evidence characteristics of primed prestimulated proinflammatory cells, similar to data observed in SLE and HIV.

Adult↗
PubMed2006

Clinical effects of online dialysate and infusion fluids.

Online hemodiafiltration appears to be the most effective technique of renal replacement therapy in many respects. Removal of small and high-molecular weight substances is enhanced. Modern technology ensures a safe, online production of reinfusion fluids. Nonetheless, stringent maintenance rules are required for the production of sterile and nonpyrogenic-dialysate solutions. In this review, we will critically review the state of the art of the clinical effects derived from the use of ultrapure dialysate and the online production of dialysate fluids in high-flux hemodiafiltration.

Bacteria↗
PubMed2006

Dialysis patients and cardiovascular problems: Can technology help solve the complex equation?

Patients with end-stage kidney disease undergoing chronic hemodialysis (HD) present higher mortality rates compared with the general population. Once patients are on HD, the risk of cardiovascular death is approximately 30 times higher than in the general population and remains 10-20 times higher after stratification for age, gender, and the presence of diabetes. About half the deaths of patients on dialysis are attributed to cardiovascular causes including coronary heart disease, cerebrovascular disease, peripheral vascular disease, and heart failure. The cardiovascular burden of the HD patient arises from three different sources: risks inherent to the patient and the uremic syndrome, traditional risk factors, and risk factors related to the dialysis therapy. Based on these considerations and the fact that several aspects of the dialysis procedure can either add to the cardiovascular burden or modify the existing burden, new technologies should be directed towards the approach of a potential 'cardioprotective dialysis therapy'; such an approach may be facilitated by the application of new techniques and advanced dialysis machines. Created to make dialysis easy and safe, new machines feature several options that make patient monitoring and online hemodiafiltration therapy routine procedures. These and other features will possibly make dialysis better tolerated and more efficient in protecting patients from undesirable or potentially fatal cardiovascular events.

Age Factors↗
PubMed2006

Oxidant and carbonyl stress-related apoptosis in end-stage kidney disease: impact of membrane flux.

Apoptosis is a highly regulated process which mostly affects cell-mediated immunity. In this open-label, randomized, prospective clinical study, we determined the impact in 10 hemodialysis patients treated with high-, medium-, and low-flux membranes on spontaneous or plasma-induced apoptosis, on monocytes, as well as on oxidant and carbonyl stress. High- and medium-flux membranes significantly reduced patients' plasma-dependent proapoptotic activity on U937 monocytic cell lines. Patients who had the highest levels of plasma-induced proapoptotic activity exhibited the highest plasma levels of advanced oxidation protein products (AOPPs) and carbonyls. Plasma carbonyl residues but not AOPPs were significantly lowered. Finally, a significant correlation could be drawn between the extent of plasma-induced proapoptotic activity and both plasma carbonyl and AOPP levels.

Adult↗
PubMed2005

Early isovolaemic haemofiltration in oliguric patients with septic shock.

OBJECTIVE: To evaluate the effects of early short-term, isovolaemic haemofiltration at 45 ml/kg/h on physiological and clinical outcomes in patients with septic shock. DESIGN: Retrospective study before and after a change of unit protocol (study period 8 years). SETTING: Intensive care unit of metropolitan hospital. PATIENTS: Eighty patients with septic shock. INTERVENTIONS: Introduction of a new septic shock protocol based on early isovolaemic haemofiltration (EIHF). In the pre-EIHF period (before), 40 patients received conventional supportive therapy. In the post-EIHF period (after), 40 patients received EIHF at 45 ml/kg/h of plasma-water exchange over 6 h followed by conventional continuous venovenous haemofiltration (CVVH). Anticoagulation policy remained unchanged. MEASUREMENTS AND MAIN RESULTS: The two groups were comparable for age, gender and baseline APACHE II score. Delivered haemofiltration dose was above 85% of prescription in all patients. PaO2/FiO2 ratio increased from 117+/-59 to 240+/-50 in EIHF, while it changed from 125+/-55 to 160+/-50 in the control group (p<0.05). In EIHF patients, mean arterial pressure increased (95+/-10 vs 60+/-12 mmHg; p<0.05), and norepinephrine dose decreased (0.20+/-2 vs 0.02+/-0.2 microg/kg/min; p<0.05). Among EIHF patients, 28 (70%) were successfully weaned from the ventilator compared with 15 (37%) in the control group (p<0.01). Similarly, 28-day survival was 55% compared with 27.5% (p<0.05). Length of stay in the ICU was 9+/-5 days compared with 16+/-4 days (p<0.002). CONCLUSIONS: In patients with septic shock, EIHF was associated with improved gas exchange, haemodynamics, greater likelihood of successful weaning and greater 28-day survival compared with conventional therapy.

Acute Kidney Injury↗
PubMed2005

Interleukin-8 is a powerful prognostic predictor of all-cause and cardiovascular mortality in dialytic patients.

BACKGROUND: Cohort studies have demonstrated an association between C-reactive protein (CRP) and interleukin-6 (IL-6) and all-cause and cardiovascular mortality in end-stage renal disease (ESRD) patients. Interleukin-8 (IL-8) appears to be not only the plasma expression of the acute-phase response but also a direct pathogenetic mediator of the atherosclerotic process. METHODS: To evaluate the role of IL-8 in predicting outcome, 76 chronic dialytic patients were prospectively followed for 18 months. At baseline, blood samples were taken for analysis of high-sensitivity CRP, IL-6, IL-8 and other standard laboratory analyses. RESULTS: Median IL-8 was 5.2 mg/l, therefore near half of the patients had IL-8 values within the range of 'normal limits'. IL-6 and CRP were significantly correlated (r = 0.45, p < 0.001) and a positive correlation was also found between IL-6 and IL-8 (r = 0.39, p < 0.001). The correlation coefficient between IL-6 and CRP was 0.43 (p < 0.001) and 0.50 (p < 0.001) in patients without and with history and/or clinical signs of cardiovascular disease, respectively. After a follow-up of 1.5 years, 8 patients had died from cardiovascular causes and another 7 patients for other reasons; furthermore 9 major nonfatal cardiovascular events were recorded. Stepwise regression analysis showed IL-8 as the strongest independent predictor of all-cause and cardiovascular events (p = 0.0025) even after adjustment for age and dialytic age, followed by IL-6 and CRP (p < 0.01). CONCLUSION: Despite a small population and a relatively short follow-up period, this study firstly demonstrated that IL-8 is a powerful independent predictive factor for cardiovascular and overall mortality cause in ESRD patients.

Aged↗
PubMed2005

Tailoring high-cut-off membranes and feasible application in sepsis-associated acute renal failure: in vitro studies.

BACKGROUND: As removal of pro-inflammatory cytokines is limited in conventional diffusive or convective extracorporeal therapies, we studied in two polysulphone membranes with an industrial albumin sieving coefficient of 0.05 (Type A) and 0.13 (Type B) cytokine (IL-6, IL-8, IL-1beta, IL-1ra, TNF-alpha) and plasma protein (albumin, cystatin C, total proteins) permeability profiles. Based on the convective membrane permeability, we evaluated in vitro the dialytic modality that could provide an acceptable balance between high cytokine and low albumin clearances. METHODS: Cytokine and plasma protein sieving coefficient (SC) and clearance were studied in (i) post-dilutional haemofiltration mode at 20% fixed ultrafiltration rate; (ii) haemodialysis mode (dialysate flow rate of 3 and 5 l/h); and (iii) haemodiafiltration mode (dialysate flow rate of 3 or 5 l/h with 0.5 l/h of ultrafiltrate). RESULTS: In haemofiltration mode both Type A and Type B haemodialysers at QB 150 ml/min exhibited similar median SC nearly up to 1 for IL-1beta and IL-1ra, at about 0.6 for IL-6, 0.4 for IL-8 and 0.7 for TNF-alpha, with clearance values ranging from 15 to 30 ml/min. SC were independent of blood flow and were stable throughout the whole experiment. Albumin SC was higher in Type B than in Type A and rapidly decreased from 0.2 to 0.02 and from 0.5 to 0.04 within 3 h for haemodialyser Types A and B, respectively. Cytokine SC was lower in haemodialysis than in haemodiafiltration and haemofiltration mode, and by increasing dialysate flow from 3 up to 5 l/h in both haemodialysis and haemodiafiltration mode, SC for all tested cytokines decreased. However, at 5 l/h clearances were not different or were higher, since increased amounts of dialysate outlet compensated for the decreased SC. Albumin clearances in haemodialysis and haemodiafiltration mode after 360 min at 5 l/h were 0.81 and 0.91 ml/min, respectively. CONCLUSIONS: Our studies show that a mixed convective and diffusive technique ensures high cytokine clearances with an acceptable loss of albumin.

Acute Kidney Injury↗
PubMed2005

Comparison of 3 automated assays for C-reactive protein in end-stage renal disease: clinical and epidemiological implications.

Chronic inflammation has been repeatedly reported in individuals undergoing hemodialysis. C-reactive protein (CRP) is considered a marker of chronic inflammation, as well as a mediator of the atherosclerotic process. Clinical and epidemiologic studies are based on plasma values obtained with the use of various automated methods. Our aim was to test 3 commercially available methods and compare the values obtained with the use of these tests in a population of individuals undergoing hemodialysis. We compared the following methods: immunoturbidimetry (AU2700 biochemistry analyzer; Olympus, Rungis, France) laser nephelometry (Behring Diagnostics, Marburg, Germany), and nephelometry (Beckman Instruments, Fullerton, Calif. The 3 methods were used in 3 different centers: Montpellier, France; and Pisa and Turin, Italy, respectively. We prepared samples for the estimation of imprecision values (ie, coefficient of variation [CV]) from the plasma of normal patients by adding purified C-reactive protein at concentrations ranging from 2.6 to 180 mg/L for intraassay variation and concentrations of 0, 1, 2, 3, 5, 10, 20, 50, 100, 150, and 180 mg/L for interassay variation. Intraassay imprecision was determined with the use of 10 replicate analyses on the same sample of the same day. We assessed interassay imprecision using the same sample, divided into aliquots and measured on 5 consecutive days. Agreement between methods was assessed on predialysis serum samples collected from patients with stable chronic kidney disease who were undergoing long-term hemodialysis at the 3 different centers (Montpellier,192; Pisa, 56; Turin,98). Serum was separated from the red cells and stored in 3 aliquots at -70 degrees C until it could be analyzed. Samples were thawed only once, circulated among the 3 centers, and each tested with all 3 of the methods. The Beckman method yielded the most precise results, with intraassay CVs ranging from 1 to 2 and interassay CVs ranging from 1 to 4. The Behring method was the least precise, with intraassay and interassay CVs ranging from 12 to 15 and 7 to 16, respectively. The results of the Olympus method fell between those of the other 2 methods. Agreement between the results of the Olympus and Behring methods was satisfactorily. The Beckman and Olympus methods yielded, on average, similar results over the entire range of CRP values. We detected significant disagreement between the Beckman method and the other 2 methods, obtaining results 10 to 100 times lower with the Beckman method. This became evident in terms of kappa-statistics. Our findings emphasize the need for careful assessment of the methods used to detect CRP in serum samples. Failure to do so may ultimately have a negative impact on the real relevance of CRP as a marker and on the role of chronic implication particularly in epidemiologic studies.

Biomarkers↗
PubMed2005

Dialysis patients and cardiovascular problems: can technology solve the complex equation?

Patients with end-stage kidney disease undergoing chronic hemodialysis present higher mortality rates compared with the general population. Once patients are on hemodialysis, the risk of cardiovascular death is approximately 30-times higher than the general population, and still remains 10- to 20-times higher after stratification for age, gender and presence of diabetes. Approximately half of patient deaths on dialysis are attributed to cardiovascular causes, including coronary heart disease, cerebrovascular disease, peripheral vascular disease and heart failure. The cardiovascular burden of the hemodialysis patient arises from three different sources: risks inherent to the patient and the uremic syndrome, traditional risk factors and risk factors related to the dialysis therapy. Based on these considerations and the fact that several aspects of the dialysis procedure can cause either a cardiovascular burden or modify the burden already present, new technologies should be directed towards the approach of a possible 'cardioprotective dialysis therapy'. This approach may significantly contribute new techniques and new dialysis machines. Born to make dialysis easy and safe, the new machines feature several options that make monitoring and online hemodiafiltration a simple routine. These and other features could make dialysis better tolerated and more efficient in protecting from fatal cardiovascular events.

Biotechnology↗
PubMed2004

Interleukin-6 is a stronger predictor of total and cardiovascular mortality than C-reactive protein in haemodialysis patients.

BACKGROUND: Despite the well known association between interleukin-6 (IL-6) and cardiovascular mortality, no study has so far verified whether IL-6 adds prognostic information to that provided by C-reactive protein (CRP). METHODS: A cohort of 218 haemodialysis patients from four different dialytic centres was followed-up retrospectively. Plasma IL-6 and CRP concentrations were determined. Full information on co-morbidities was available in 162 patients. RESULTS: With respect to the lowest quartile (< 3.6 pg/ml for IL-6, and < 2.2 mg/l for CRP), the crude relative risk (RR) of death from all causes of the upper quartile (> 13.9 pg/ml for IL-6, and > 12.8 mg/l for CRP) was 5.20 (95% confidence interval 2.06-13.011) for IL-6 and 3.16 (1.41-7.12) for CRP. When both variables were included, the estimates were 4.10 (1.30-12.96) for IL-6 and 1.29 (0.47-3.57) for CRP. As to continuous variables, the relationship between both variables and mortality tended to level off for the highest values, but became fairly linear after log transformation of the variables. For one unit SD of the log (variable), the RR was 2.09 (1.52-2.88) for IL-6 and 1.66 (1.23-2.24) for CRP. When they were included in the same model, the estimates were 1.90 (1.18-2.82) for IL-6 and 1.16 (0.81-1.66) for CRP. CONCLUSIONS: IL-6 has a stronger predictive value than CRP for cardiovascular mortality and provides independent prognostic information, while conveying most of that provided by CRP.

Biomarkers↗
PubMed2004

Regional citrate anticoagulation in critically ill patients treated with plasma filtration and adsorption.

BACKGROUND: In high-risk bleeding conditions conventional systemic anticoagulation with heparin is a contraindication to renal replacement therapy. We evaluate the feasibility and safety of regional citrate anticoagulation in high-risk bleeding conditions during coupled plasma filtration adsorption (CPFA). METHODS: Thirteen critically ill patients (9 severely burned, 4 polytraumas) with septic shock and acute renal failure treated with CPFA-CVVHD by using bicarbonate-based solutions (heparin-CPFA group, 58 sessions) or with CPFA-CVVHF using citrate (citrate-CPFA group, 36 sessions). RESULTS: Plasma flow and used cartridges showed no differences between the citrate-CPFA and heparin-CPFA groups, while lost clotted cartridges were significantly lower in the citrate-CPFA group. Blood ionized calcium (iCa2+), Ca2+ infusion, pH and bicarbonates remained constant during citrate-CPFA, with no difference between pre- and post-cartridge plasma citrate. A significant positive correlation between iCa2+ in blood and ultrafiltrate was present. CONCLUSIONS: These suits demonstrate the feasibility and safety of regional citrate anticoagulation in severely burned and polytrauma septic patients treated by CPFA.

Acute Kidney Injury↗
PubMed2003

Coupled plasma filtration adsorption.

BACKGROUND: Severe sepsis and septic shock are perhaps the major cause of morbidity and mortality in Intensive Care. Their pathogenesis is only partly understood. Circulating peptides and lipid-derived substances (so-called mediators), however, appear to participate in the development of organ dysfunction. It might be possible to treat plasma in such a way that the injurious effect of mediators can be attenuated. INVESTIGATIONS: Several ex vivo studies have shown that it is technically possible to adsorb mediators by means of specially developed sorbents. The application of these sorbents to the treatment of plasma in animals with experimental sepsis has shown that several markers of inflammation can be attenuated and that animal survival can be increased. We have recently transferred such technology to the treatment of human septic shock using a technique called Coupled Plasma Filtration Adsorption (CPFA). CPFA was found to attenuate the hypotension of septic shock and to dramatically alter the immuno-paralytic toxicity of septic plasma. Monocytes of patients treated with CPFA underwent a major improvement in their ability to respond to endotoxin. CONCLUSIONS: CPFA represents a promising new approach to blood purification in sepsis. The findings associated with its application to humans highlight the importance of continuing to investigate blood purification as a possible approach to the treatment of septic shock, the potential usefulness of the humoral theory of sepsis, and the dominant state of immunosuppression associated with established septic shock.

Adsorption↗