High-Flux Dialysis: Clinical, Biochemical, and Proteomic Comparison with Low-Flux Dialysis and On-Line Hemodiafiltration.

Hemodiafiltration on-line (on-line HDF) is a more efficient treatment than low-flux hemodialysis (HD). Unfortunately, it cannot be proposed to all patients. The aim of this study was to evaluate the safety, efficiency, and mechanisms of removal of toxins with high-flux HD vs. low-flux HD and on-line HDF. Randomized cross-over study designed to evaluate efficiency and tolerability of high-flux HD vs. low-flux HD in aged patients; to compare by means of biochemical and proteomic analyses the efficiency and mechanisms of removal of toxins with high-flux HD vs. on-line HDF. The removal of small toxins was similar with high-flux and low-flux HD. ß2-microglobulin was removed only with high-flux HD, which had an excellent tolerability. The efficiency of high-flux HD was similar to on-line HDF. Proteomic analysis demonstrated that only high-flux membranes remove and adsorb small proteins. High-flux HD may be an efficient alternative to on-line HDF.

ß-trace protein is highly removed during haemodialysis with high-flux and super high-flux membranes.

BACKGROUND: Serum ß-trace protein (ßTP, MW 23-29 kDa) is a marker of GFR impairment in renal patients. Recent papers propose to predict residual renal function (RRF) in maintenance haemodialysis (MHD) patients from serum concentrations of ßTP and other small proteins, avoiding the collection of urine. Few data are available on the removal of ßTP in patients treated with dialysis membranes with different flux characteristics. The aim of this study was to evaluate the effects of haemodialysis with low-flux, high-flux and super high-flux membranes on serum concentrations of ßTP in MHD patients with null RRF. METHODS: Serum ßTP concentrations were measured before and after the first dialysis of the week in 51 MDH patients treated by low-flux (n = 24), high-flux (n = 17), or super high-flux (n = 10) membranes. The removal of ß2-microglobulin (ß2M, MW 11.8), cystatin C (Cys, MW 13.3), urea and creatinine was also analyzed. RESULTS: Low-flux membranes did not remove ßTP, ß2M and Cys whose concentration increased at the end of dialysis. High-flux membrane removed more efficiently ß2M and Cys than ßTP. Super high-flux membrane had the highest efficiency to remove ßTP: mean reduction ratio (RR) 53.4%, similar to ß2M (59.5%), and Cys (62.0%). CONCLUSIONS: In conclusion, the plasma clearance of small proteins and particularly of ßTP is dependent from the permeability of the dialysis membranes Therefore, the reliability of the formulas proposed to predict RRF from serum ßTP and other LMWP may be affected by the different permeability of the dialysis membranes.

Direct evidence that late Neanderthal occupation precedes a technological shift in southwestern Italy.

OBJECTIVES: During the middle-to-upper Paleolithic transition (50,000 and 40,000 years ago), interaction between Neanderthals and Homo sapiens varied across Europe. In southern Italy, the association between Homo sapiens fossils and non-Mousterian material culture, as well as the mode and tempo of Neanderthal demise, are still vividly debated. In this research, we focus on the study of two human teeth by using 3D geometric morphometric approaches for a reliable taxonomical attribution as well as obtaining new radiometric dates on the archeological sequence. MATERIAL AND METHODS: This work presents two lower deciduous molars uncovered at Roccia San Sebastiano (Mondragone-Caserta, Italy), stratigraphically associated with Mousterian (RSS1) and Uluzzian (RSS2) artifacts. To obtain a probabilistic attribution of the two RSS teeth to each reference taxa group composed of Neanderthals and Homo sapiens, we performed and compared the performance of three supervised learning algorithms (flexible discriminant analysis, multiadaptive regression splines, and random forest) on both crown and cervical outlines obtained by virtual morphometric methods. RESULTS: We show that RSS1, whose Mousterian context appears more recent than 44,800-44,230 cal BP, can be attributed to a Neanderthal, while RSS2, found in an Uluzzian context that we dated to 42,640-42,380 cal BP, is attributed to Homo sapiens. DISCUSSION: This site yields the most recent direct evidence for a Neanderthal presence in southern Italy and confirms a later shift to upper Paleolithic technology in southwestern Italy compared to the earliest Uluzzian evidence at Grotta del Cavallo (Puglia, Italy).

A vitamin E-coated polysulfone membrane reduces serum levels of inflammatory markers and resistance to erythropoietin-stimulating agents in hemodialysis patients: results of a randomized cross-over multicenter trial.

BACKGROUND: Oxidative stress is prevalent in dialysis patients and has been implicated in the pathogenesis of cardiovascular disease and anemia. Vitamin E is a fat-soluble antioxidant that plays a central role in reducing lipid peroxidation and inhibiting the generation of reactive oxygen species. The aim of this cross-over randomized study was to compare the effects of a vitamin E-coated polysulfone (Vit E PS) membrane and a non-vitamin E-coated polysulfone (PS) membrane on inflammatory markers and resistance to erythropoietin-stimulating agents (ESAs). METHODS: After a 1-month run-in period of standard bicarbonate dialysis with a synthetic membrane, 62 patients of both genders, and older than 18 years, dialysis vintage 48 ± 27 months, BMI 22 ± 3 (from 13 different dialysis units) were randomized (A-B or B-A) in a cross-over design to Vit E PS (treatment A) and to PS (treatment B) both for 6 months. C-reactive protein (CRP) and interleukin-6 (IL-6) concentrations were determined by a sandwich enzyme immunoassay at baseline and every 2 months; red blood cell count, ESA dose and ESA resistance index (ERI) were assessed monthly. RESULTS: Hemoglobin (Hb) levels significantly increased in the Vit E PS group from 11.1 ± 0.6 g/dl at baseline to 11.5 ± 0.7 at 6 months (p < 0.001) and remained unchanged in the PS group. Although ESA dosage remained stable during the observation periods in both groups, ERI was significantly reduced in the Vit E PS group from 10.3 ± 2.2 IU-dl/kg/g Hb week at baseline to 9.2 ± 1.7 at 6 months (p < 0.001). No significant variation of ERI was observed in the PS group. A significant reduction in plasma CRP and IL-6 levels was observed in the Vit E PS group: CRP from 6.7 ± 4.8 to 4.8 ± 2.2 mg/l (p < 0.001) and IL-6 from 12.1 ± 1.4 to 7.5 ± 0.4 pg/ml (p < 0.05). In the PS group, CRP varied from 6.2 ± 4.0 to 6.4 ± 3.7, and IL-6 from 10.6 ± 2.1 to 9.6 ± 3.5 (p = n.s.). CONCLUSIONS: Treatment with Vit E PS membranes seems to lead to a reduction in ESA dosage in HD patients; in addition, a low chronic inflammatory response may contribute to a sparing effect on exogenous ESA requirements.

Effects of the incubation in vitro with sorbents on serum proteomic pattern and cytokine concentration in cancer patients during chemotherapy--preliminary results.

INTRODUCTION: Cancer and treatment by chemotherapy often produce abnormalities in endogenous cytokine, chemokine, and inflammatory mediator production. Sorbent-based adsorption therapies have been used to remove cytokines in diverse human diseases. AIM: The aim of this study was to evaluate the effects of chemotherapy on serum proteomic pattern and cytokine concentration, and to evaluate the ex vivo feasibility of using sorbents to remove cytokines, chemokines and other proteins in adult cancer patients undergoing chemotherapy with fluorouracil or carboplatin-taxane combinations. PATIENTS AND METHODS: Serum samples of three female adult patients (one affected by rectal cancer and two by ovarian cancer) were examined before and on the fourth day of the first cycle of chemotherapy with fluorouracil (rectal cancer patient) or carboplatin-taxane combination (ovarian cancer patients). The analysis was performed, by means of luminex technology and with a proteomic approach, on native serum samples, and on the same sera after 2 hours of in vitro incubation with a synthetic based styrenic divinylbenzene resin. RESULTS: Chemotherapy determined variable effects on serum concentration of cytokines, while the incubation in vitro of patients serum samples with the resin induced a significant decrease (>80%) in serum concentration of different chemokines, cytokines, growth factors and proteins. The proteomic approach, using SDS PAGE and 2-DE highlighted differences in protein expression between sera from healthy controls and cancer patients. Proteomic analysis demonstrated also variations in the expression of proteins, particularly those with low-molecular weight, due to chemotherapy. Finally, the incubation in vitro of serum samples with sorbents induced a general reduction of protein expression. Within the cancer patients maps, 10 spots were chosen for identification with MALDI-TOF analysis. CONCLUSION: The incubation in vitro with sorbents normalized the over-expression of different proteins and cytokines induced by chemotherapy, suggesting further evaluation as a possible adjuvant treatment.