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Biomedical subjects

Valeria Bordoni

Publications and source records attributed to Valeria Bordoni.

10 recordsLinked to original sources

Interpreting the mechanisms of continuous renal replacement therapy in sepsis: the peak concentration hypothesis.

Severe sepsis and septic shock are the primary causes of multiple organ dysfunction syndrome (MODS), which is the most frequent cause of death in intensive care unit patients. Many water-soluble mediators with pro- and anti-inflammatory action such as TNF, IL-6, IL-8, and IL-10 play a strategic role in septic syndrome. In intensive care medicine, blocking any one mediator has not led to a measurable outcome improvement in patients with sepsis. CRRT is a continuously acting therapy, which removes in a nonselective way pro- and anti-inflammatory mediators; "the peak concentration hypothesis" is the concept of cutting peaks of soluble mediators through continuous hemofiltration. Furthermore, there is evidence of increased efficacy of high-volume hemofiltration compared to conventional CVVH, and other blood purification techniques that utilize large-pore membranes or sorbent plasmafiltration are conceptually interesting.

Acute Kidney Injury↗

Mononuclear leukocyte apoptosis in haemodialysis patients: the role of cell thiols and vitamin E.

BACKGROUND: An increased apoptotic rate of peripheral blood mononuclear leukocytes (PBMLs) in haemodialysis (HD) patients has been reported in several studies, but its underlying mechanisms remain poorly understood. Oxidant stress is a well known cause of cell damage, and several lines of evidence suggest that it might influence the induction and signalling steps of mononuclear cell apoptosis through different mechanisms so as to provoke disturbances of the intracellular pool of thiols (SHi). In this study, we investigated the in vitro apoptotic rate and SHi of PBMLs in end-stage renal disease (ESRD) patients on HD or peritoneal dialysis (PD). METHODS: Apoptosis and SHi were evaluated in vitro in PBMLs obtained from 40 ESRD patients (HD, n = 30 and PD, n = 10) and 10 healthy controls. A subgroup of HD patients was also studied before and after 1 month of treatment with a vitamin E-coated dialyser (CL-E). Cell thiols and viability were also assessed in the monocyte-like cell line U937 and PBMLs after incubation in the presence of uraemic plasma with or without supplementation of the antioxidants vitamin E (70 micro M) or N-acetyl-cysteine (NAC) (0.5 mM). RESULTS: After 24 h in culture, the PBMLs of HD patients, but not those of CAPD patients, showed an apoptotic rate twice that of healthy controls and a 40% decrease of SHi levels (P < 0.01 in both). A negative correlation between the apoptotic rate and SHi was observed in both patients and controls (r = 0.648, P < 0.001). Plasma and ultrafiltrate samples from HD patients contained solutes (mainly in the low-middle molecular weight range) able to trigger apoptosis and oxidative stress in U937 cells. The treatment of HD patients with CL-E, as well as the in vitro supplementation of U937 cells with vitamin E or NAC during the exposure to uraemic plasma, decreased the rate of apoptosis and partially restored SHi. CONCLUSIONS: This study showed an association between an increased apoptotic rate and decreased SHi in PBML of HD patients, but not of CAPD patients. These changes are partially due to different pro-apoptogens that accumulate in the plasma and are at least partially prevented by exogenous antioxidants able to restore SHi, such as vitamin E or thiol suppliers.

Aged↗

Hemodialyzer: from macro-design to membrane nanostructure; the case of the FX-class of hemodialyzers.

Very few innovations have characterized the different components of the hemodialyzers in the past 20 years. Most improvements have concerned membrane biocompatibility. In this article, we focus our attention on the most recent advances in hemodialyzer components from the macro design of the unit to the nanostructure of the membrane. For this purpose, we took as an example the FX class of hemodialyzers (FMC, Bad Homburg, Germany). The studied devices were chosen as an example representing some of the most recent hemodialyzers and are well suited to describe technical innovations occurring in the field of dialyzer technology. In vitro and in vivo studies were performed to characterize hemodynamic parameters of three models (1.4-1, 8, and 2.2 m2) and to determine membrane permeability, sieving coefficients, and solute clearances. The units were characterized by a relatively high resistance of the blood and dialysate compartments, leading to an increased internal filtration if compared with similar hemodialyzers of other series. Nevertheless, the flow distribution in both compartments was homogeneous and well balanced. This effect was obtained by the improved blood and dialysate ports design, the increased packing density of the fibers and a reduction of the inner diameter of the fibers from 200 to 180 microm. At the same time, the sieving coefficients for middle-large solutes such as beta2 microglobulin and insulin were higher than those observed in standard high flux dialysers. The same effect was noted for the clearance values of these solutes. This was observed in the absence of significant albumin leakage. These results were obtained thanks to a new nano-controlled spinning technology applied to the fiber. The innermost layer of the membrane is in fact characterized by a homogeneous porosity, with increased number of pores of large dimension but a sharp cutoff of the membrane excluding albumin losses. In conclusion, new technologies and new diagnostic tools today allow for improvement in hemodialyzer design from its macro-components to its nano-structure. The application of nanotechnology to hemodialysis will probably contribute to further developments in hemodialyzer manufacturing.

Equipment Design↗

In vitro removal of therapeutic drugs with a novel adsorbent system.

BACKGROUND/AIMS: Substances in the middle molecular weight range have been shown to play a significant pathogenetic role in as diverse disorders as end-stage renal disease and multiple organ failure. To overcome the limitations in the amount removed by hemofilters, new sorbents with a high biocompatibility are actively being developed. Furthermore, biocompatible sorbents by their nonspecific adsorptive behavior could have great impact on detoxification treatment in exogenous intoxications. We performed an in vitro evaluation of a newly developed highly biocompatible sorbent cartridge (Betasorb((R))), examining its adsorptive capacity concerning therapeutic drugs. METHODS: Uremic blood spiked with a range of therapeutic drugs was recirculated for 2 h in an in vitro hemoperfusion circuit containing a Betasorb device for hemoperfusion. The drug concentrations before and after the passage of the cartridge were measured, and the total amount removed was calculated. RESULTS: The sorbent showed effective removal of glycopeptide antibiotics, digoxin, theophylline, phenobarbital, phenytoin, carbamazepine, and valproic acid. Moderate removal could be demonstrated for tacrolimus and cyclosporine A; aminoglycosides were removed to a small extent only. CONCLUSION: Betasorb hemoperfusion shows a potent adsorptive capacity concerning therapeutic drugs (except aminoglycosides) and could be of major value in the treatment of intoxications. On the other hand, drug monitoring and possible adjustments are necessary during Betasorb hemoperfusion to maintain the therapeutic ranges of the drugs in blood.

Adsorption↗

APD prescription: achieving the adequacy goals.

In the last few years, automated peritoneal dialysis (APD) has undergone considerable improvements due to technological developments. The definition of a minimal dose of peritoneal dialysis (PD) has not yet been completely assessed. Appropriate use of APD requires an evaluation of dialytic efficiency in terms of dialytic indexes and their targets. Many dialytic treatment modalities have been performed in order to achieve adequacy targets. Some aspects have to be taken into consideration to reach the optimal dialytic dose: optimizing mass transfer in correlation with intraperitoneal volumes, prescribing tailored treatment modalities according to different characteristics of peritoneal membranes and individual patient needs, and performing more biocompatible treatments using different glucose profiling and alternative physiologic PD fluids. New high-flow techniques such as continuous flow PD can ensure better urea and creatinine clearances and ultrafiltration rates, leading to a higher utilization of the APD modality.

Automation↗