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Biomedical subjects

A Albertazzi

Publications and source records attributed to A Albertazzi.

At least 37 records · Page 2Linked to original sources

Role of dyslipidemia in the progression of chronic renal disease.

The connection between lipids and the rate of progression of chronic renal disease was retrospectively examined in 70 patients who were divided into 2 groups according to their baseline creatinine clearance (CCr): Group 1 (Gp1) contained 30 patients with CCr 60-40 mL/min followed for 40.0 +/- 13.3 months; Group 2 (G2) contained 40 patients with CCr 39-15 mL/min followed for 39.0 +/- 18.2 months. The following parameters were considered: basal and final CCr proteinuria per unit of CCr (UProt/CCr); the difference between final and basal UProt/CCr (delta UProt/CCr); the change in CCr/month (delta CCr); baseline triglycerides (TG), total (TC), HDL (HDLC) and LDL (LDLC) cholesterol, Apo AI, Apo B, Lp(a). Besides in basal CCr the 2 groups significantly differed in the final CCr, final UProt/CCr, delta UProt/CCr, delta CCr. No differences were observed concerning lipid parameters except for Lp(a) (G1 14.8 +/- 13.6, G2 28.7 +/- 27.4 mg/dL; p < 0.05). Baseline TG (G1 184.1 +/- 61.3, G2 187.5 +/- 72.1 mg/dL) and Apo B (only G2 1.05 +/- 0.32 g/L) were significantly higher than normal subjects and the Apo AI/Apo B ratio (G1 1.42 +/- 0.43, G2 1.33 +/- 0.45) were significantly lower than in normal subjects. delta CCr, while inversely correlated in both groups with delta UProt/CCr (p < 0.01), only in G2 did it correlate directly with the Apo AI/Apo B ratio (p < 0.05) and inversely with Apo B and LDLC (p < 0.05). Although a correlation between Lp(a) and delta CCr was not found, 20/22 patients (3/5 G1, 17/17 G2) with a level > 30 mg% ran a progressive course. A natural progression of CRI, heralded by an increasing UProt, is highly frequent when baseline CCr is < 40 mL/min; only then lipids seem to add a burden to the renal damage.

Apolipoproteins↗

Efficacy and tolerability of recombinant human erythropoietin treatment in pre-dialysis patients: results of a multicenter study.

Chronic renal failure is characterized by a normochromic normocytic anemia, the severity of which generally increases during progression toward uremia. The purpose of the study was to evaluate the efficacy and safety of recombinant human erythropoietin (rHu-EPO) given subcutaneously (s.c.), the dose required to reach and maintain Hb levels within 10 and 11 g% and its effects, if any, on the progression of chronic renal failure. Eighty-four pre-dialysis patients (46 F, 38M, age 61.7+/-13.9 years) with Hb levels between 6 and 9 g% and serum creatinine ranging from 3 to 9 mg/dl were treated with s.c. rHu-EPO (2000 U/twice weekly). After 6 weeks, if Hb increase was below 1 g%, 1000 U of s.c. rHu-EPO were added at each administration (3000 U twice weekly). Once the Hb target was reached (10-11 g%), the rHu-EPO weekly dose was halved and administration reduced to once weekly. The patients showed a significant rise in mean Hb values (p<0.001) after 3 months. Mean Hb values were as follows: 8.00+/-0.77 g% (pretreatment), 9.35+/-1.0 (3rd month), 10.06+/-1.04 (6th month), 10.25+/-0.62 g% (12th month). The mean rHu-EPO doses were 4000 U/w (start of the study), 3592+/-1685 U/w (6th month), 2840-/+1178 U/w (12th month). Renal function was evaluated by plotting the reciprocal of serum creatinine values vs time with a two period comparison: period A (retrospective-8 mo); period B (prospective-12 mo). The residual renal function was not impaired by rHu-EPO therapy. Meanwhile, no relevant modifications were observed in mean blood pressure values. Low doses of s.c. rHu-EPO were well tolerated, safe and effective; this therapeutic approach should therefore be considered for the improvement of anemia in pre-dialysis patients. A slow and gradual correction of anemia induces an improved sense of well being and a more active of life style.

Adolescent↗

Platelet-neutrophil interactions during hemodialysis: a proposed biocompatibility approach.

Platelet interaction with neutrophils may occur to a significant degree during hemodialysis (HD). We have recently shown that the enhanced neutrophil reactive oxygen species (ROS) production during the early phase of HD with cuprophan (CUP) is sustained by neutrophils which have bound platelets through P-selectin (CD62P). The evaluation of platelet-neutrophil interactions during dialysis offers the novel aspect of cell-cell interactions as a new parameter for studying the biocompatibility of dialyzer membranes. By the use of flow cytometry techniques, the present study was set up to analyze intradialytic platelet-neutrophil coaggregate formation and neutrophil ROS (hydrogen peroxide) production from 6 HD patients each dialysed with CUP, cellulose diacetate (CDA), polymethylmethacrylate (PMMA), and polyacrylonitrile (PAN) in a cross-over clinical trial. Platelet-neutrophil coaggregate formation (percentage of neutrophil cells positive for CD62P) and ROS production by neutrophils (total population; CD62P+ cells; CD62P- cells) were determined before HD and after 10', 20'and 40'. CD62P+ neutrophils significantly increased during HD with CUP (10', 20', 40'), PMMA (20') and CDA (20), while no change was observed with PAN. The difference between CUP and the other membranes was significant at 10', 20' and 40'; at 20', PMMA vs PAN p<0.005. ROS production by total neutrophil population significantly increased with CUP (10', 20), PMMA (20) and CDA (20'). The increase with CUP was higher at 10' when compared to CDA (p<0.020) or PAN (p<0.005), and at 20' versus the other three membranes; at 20' PMMA vs PAN p<0.005. Only neutrophils gated in neutrophil-platelet coaggregate areas (CD26P+ neutrophils) produced hydrogen peroxide. ROS production by CD62P+ neutrophils significantly increased with CUP (10', 20), PMMA (20') and CDA (20'). The increase with CUP was significantly (p<0.0002) higher than the other three membranes at 10' and 20'; at 20', PMMA vs PAN p<0.02. With each membrane, ROS production by CD62P- neutrophils showed no significant change at any time point during HD. The results of the present study indicate that interactions between platelets and neutrophils can mediate some pathophysiological abnormalities associated with hemodialysis treatment. Our data show that cellulose diacetate, a modified cellulosic membrane, exhibits a biocompatibility profile in terms of platelet-neutrophil interactions improved as compared to the parent cellulose membrane and comparable to that of some synthetic membranes. Our data also show that there is considerable variability in the biocompatibility of synthetic membranes. Though cellulosic membranes are generally considered as being less biocompatible than synthetic membranes, our results indicate that classification of membranes by biocompatibility is more complex than a simple division into cellulosic and synthetic membranes, especially with the advent of modified cellulosic membranes.

Acrylic Resins↗

Neutrophil reactive oxygen species production during hemodialysis: role of activated platelet adhesion to neutrophils through P-selectin.

Platelet interaction with leukocytes can occur to a significant degree during hemodialysis, but it remains to be determined what pathophysiological consequences stem from the intradialytic formation of platelet-leukocyte coaggregates. By the use of flow cytometry techniques, this study was set out to analyze intradialytic platelet-neutrophil coaggregate formation and neutrophil hydrogen peroxide production from 10 end-stage renal disease patients each dialyzed with cuprophane and polyacrylonitrile membranes. Platelet-neutrophil coaggregates increased during dialysis with cuprophane, whereas no changes occurred with polyacrylonitrile membranes. Dialysis with cuprophane, unlike that with polyacrylonitrile, also resulted in a significant increase in neutrophil hydrogen peroxide production 10 min after dialysis initiation which persisted at significantly higher levels than predialysis values through the first 20 min. We found that the increased hydrogen peroxide production by neutrophils essentially occurred in concomitance with neutrophil-platelet coaggregation. Intracellular fluorescence representing hydrogen peroxide formation significantly increased through the first 20 min of cuprophane dialysis in neutrophils aggregated to platelets. By contrast, no change occurred in neutrophils not aggregated to platelets. Neutrophils which had formed aggregates with platelets produced higher hydrogen peroxide levels, as assessed by significantly higher fluorescence values, than non-aggregate-forming neutrophils at all time points tested. The phenomenon was duplicated in vitro when ADP-activated normal platelets were incubated with neutrophil cells but was largely inhibited when ADP-activated platelets were treated with anti-P-selectin antibody before incubation with neutrophils. These results strongly suggest that platelet-neutrophil aggregates occurring during hemodialysis, representing cell-cell interactions with pathophysiological effects, may serve as a new parameter to assess biocompatibility.

Adenosine Diphosphate↗

Thyroid function and plasma selenium in chronic uremic patients on hemodialysis treatment.

It has been shown recently that Selenium (Se), an essential trace element for humans, is involved in the regulation of thyroid function, since the enzyme that catalyzes the liver conversion of the thyroid hormone T4 to the more active form T3 is a selenoenzyme. In chronic uremic patients, low blood Se levels as well as thyroid function abnormalities are often found. The present study was carried out to verify whether any correlation exists between Se levels and thyroid function, and to evaluate possible changes in hormonal pattern during Se supplementation in 10 chronic uremic patients on hemodialysis (HD) treatment. Se was supplemented orally as sodium selenite over six consecutive months. Basic plasma Se levels were significantly lower in patients than in normal controls. Right from the start of Se supplementation, plasma Se concentration promptly normalized and leveled off in the normal range throughout the study. Significant increase of FT3 and reduction of TSH levels were detected during Se supplementation. In Se-supplemented patients, a significant direct correlation was also found between reverse T3 (rT3) and TSH, and a significant inverse correlation was found between Se and TSH. Our results suggest that Se deficiency in chronic uremic patients represents a factor influencing the thyroid function and that the Se status should be determined in the evaluation of thyroid metabolism in these patients.

Administration, Oral↗

Cell-associated adhesion molecules as early markers of bioincompatibility.

BACKGROUND: Transient nature of adhesive interactions occurring during cell margination is mainly dependent on expression of selectins which are shed by activated cells. This shedding in the circulation may play an important role as anti-inflammatory mediator. Haemodialysis is also associated with P-selectin (CD62P)/sialyl-Lewis(x) (CD15s) interactions which mediate platelet-leukocyte coaggregation. We further investigated the mechanisms underlying leukocyte margination during haemodialysis. METHODS: CD15s, CD11b and CD61 expression on circulating leukocytes from patients dialysed on synthetic membranes (modified polyacrylonitrile (SPAN), polysulphone (PS), and polyacrylonitrile (AN69) was assessed by cytofluorometry in a prospective crossover trial. We measured plasma levels C3a/C3a desArg, soluble CD62P, and CD62E molecules obtained from patients and healthy individuals. RESULTS: Expression of CD11b and CD15s was upregulated on neutrophils from patients dialysed with SPAN and PS membranes during the dialysis session. A significant negative correlation was found between the expression of CD11b or CD15s molecules and neutrophil counts as well as between CD15s expression and monocyte counts during haemodialysis. As assessed by CD61 expression on leukocytes, we observed that platelets bound significantly onto both neutrophils and monocytes during dialysis with both membranes. A significant positive correlation was found between the expression of CD11b molecules and the percentage of CD61+ monocytes counts during SPAN and PS dialysis. We found a significant increase of soluble CD62P in plasma samples obtained from haemodialysed patients before the dialysis session as compared to the levels detected in plasma from healthy individuals. CONCLUSIONS: This study documents a major role of CD15s, CD11b, CD61, CD62P molecules in the transient leukocytes activation and margination during haemodialysis on synthetic membranes despite their low complement-activating properties.

Adult↗

Geographic factors and plasma selenium in uremia and dialysis.

The importance of selenium (Se) as an essential trace element for man has been increasingly recognized. Blood Se levels in chronic uremic patients are frequently reported to be lower than in controls. Definitive determination of the Se status in uremic patients, however, is hampered by the wide range of blood Se content in humans from different parts of the world. The present study was designed to assess and compare the Se status in two European populations from Rostock (Germany) and Chieti (Italy). Plasma Se levels were evaluated in healthy controls, chronic renal failure nondialyzed patients (CRF) and hemodialysis patients (HD). All Se determinations were performed in a single laboratory. The Se concentration was significantly higher (p < 0.005) in Italian healthy controls than in German healthy controls. In contrast, Se levels were similar in both CRF and HD patients from both cities. In both countries, the Se concentration in CRF and HD patients was significantly lower (p < 0.001) than in their corresponding controls, but no difference between CRF and HD was found. CRF and HD patients from the two countries showed quite similar laboratory and anthropometric data. In CRF patients in Chieti, a significant (p < 0.05) negative correlation between plasma Se and serum creatinine was found. In both HD groups, the length of time on HD and type of membrane dialyzer used did not influence the Se status. A significant positive correlation (p < 0.01) between Se levels and the protein catabolic rate was found in both HD groups. Uremia seems to be a strong factor which overrules the difference in Se levels that is present in healthy adults from different European countries. Uremia in itself may influence and level the Se concentration in patients with geographic diversity.

Adult↗

A new polymethylmethacrylate membrane for hemodialysis.

High molecular weight (MW) solutes are not removed during conventional hemodialysis (HD), and their accumulation is thought to play a role in some long-term HD complications (anemia, bone and joint pain, neuropathy, itching). The present trial was conducted to evaluate the removal capacity during in vivo HD of a new polymethylmethacrylate (PMMA) membrane (Filtryzer BK-F, 1.3 m2) compared to conventional PMMA (BK-P, 1.6 m2) and to cellulose acetate (CA, 1.3 m2). BK-F dialyzers, with a pore size of 100 A degrees and 62% porosity, are designed to remove high MW substances. Ten stable anuric RDT patients (53 +/- 13 years) were treated for one week with each membrane in a randomized sequence. Plasma concentrations of creatinine, BUN and beta 2-microglobulin (beta 2-M) were measured before (b) and after (a) HD to determine the reduction rate for these substances (%). Beta 2-M concentration after HD was corrected for changes in distribution volume. Samples of spent dialysate were collected after 3 minutes, 120 minutes and at the end of HD sessions, and appropriately treated and concentrated for HPLC analysis. The reduction rate for BUN and creatinine was similar for the 3 membranes. BK-F showed a higher beta 2-M reduction rate than BK-P (p < 0.005) or CA (p < 0.0001). HPLC analysis of dialysate showed prevalent peaks < 4 kilodaltons (kDa) throughout HD for BK-P and CA. Solutes > 10 kDa were infrequently detected. Peak profile during HD with BK-F was quite different, showing a predominant peak > 50 kDa which also included albumin. However, albumin loss significantly decreased after 120 minutes and at the end of dialysis compared with the 3-minute values, and was lower than that reported in CAPD patients. With BK-F a peak of MW > 500 kDa was also detected which previous studies indicated as a range characterized by the presence of erythropoiesis inhibitors. Use of the BK-F membrane in HD could afford satisfactory removal of high MW substances, thereby preventing or controlling some long-term HD complications such as anemia or beta 2-M amyloid formation.

Adult↗

A major role for CD62P/CD15s interaction in leukocyte margination during hemodialysis.

We investigated expression of several antigens on neutrophils and monocytes, involved in cell adhesion, from patients hemodialyzed with cellulosic and polyacrylonitrile membranes. Among the antigens tested only the expression of CD15s and CD11b was significantly increased on neutrophils and monocytes in patients dialyzed with cellulosic membranes. No changes occurred with polyacrylonitrile membranes. Leukocyte counts from patients dialyzed with cuprophane membranes decreased at the same time as expression of cellular CD15s increased, resulting in a significant negative correlation at all time points tested. No correlation was found between the drop of monocytes and their expression of CD11b. When CD15s expression increased on neutrophils and monocytes, we observed a concomitant increase of CD62P, a specific selectin of activated platelets. When whole blood cells were incubated with complement activated serum both antigens increased but not when cells were incubated with hrC5a. We also observed that CD61, a platelet phenotypic antigen, was present on leukocytes incubated with complement activated serum. At the time when platelet-leukocyte coaggregates decreased, CD62P expression remained stable on leukocytes, suggesting that both neutrophils and monocytes are able to trap either CD62P shed by activated platelets or soluble CD62P present in normal human serum. The present study documents a major role of P-selectin (CD62P)/sialyl-Lewis x (CD15s) interaction in the transient leukocyte margination during hemodialysis.

Acrylic Resins↗

Hemodialysis with regenerated cellulosic membranes does not reduce plasma selenium levels in chronic uremic patients.

Selenium (Se) is considered an essential and very important trace element for humans. Se blood levels are frequently low in end-stage renal disease (ESRD) patients, but very little has been established concerning the mechanisms that could modify Se status in uremia, including a supposed dialysis-mediated Se depletion. In order to verify whether hemodialysis (HD) can induce a loss of Se, thereby leading or contributing to a low plasma Se concentration, we investigated the effect of HD procedure with the most commonly used regenerated cellulosic membrane (Cuprophan) on plasma Se levels in 20 uremic patients on HD for 62.5 +/- 49.4 months. Plasma Se levels were also determined in 15 chronic renal failure (CRF) nondialyzed patients and in 28 age-matched healthy controls. Se concentration was determined by atomic absorption spectrophotometry. Plasma Se levels of both HD patients (61.3 +/- 8.5 micrograms/L) and CRF nondialyzed patients (56.4 +/- 10.1 micrograms/L) were significantly lower than in normal subjects (78.3 +/- 9.7 micrograms/L, p < 0.001). In CRF nondialyzed patients, a significant (p < 0.05) negative correlation was found between the plasma Se concentration versus serum creatinine values. Within the HD group, plasma Se levels significantly increased after the HD procedure (72.8 +/- 17.2 micrograms/L, p < 0.02) together with hematocrit and total plasma protein values (p < 0.05 and p < 0.001, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Cellulose↗

Selenium in uremia.

The importance of selenium as an essential trace element for man has been increasingly recognized during the last several years. Selenium deficiency has been associated with cases of congestive cardiomyopathy, skeletal myopathy, anemia, enhanced cancer risk, elevated incidence of cardiovascular disease, immune system alterations, hair and nail changes, and abnormalities in thyroid hormone metabolism. These symptoms are frequently present in chronic uremic patients. Nevertheless, the prevalence and significance of selenium deficiency in the uremic syndrome is still not clearly defined. This article reviews the selenium status in chronic uremic patients, the supposed pathogenetic mechanisms of selenium disturbance in uremia, and the possible role of selenium deficiency on some uremic abnormalities.

Chronic Disease↗

Effects of selenium supplementation on immune parameters in chronic uraemic patients on haemodialysis.

BACKGROUND: The involvement of selenium (Se) in immune response has been increasingly recognized, cell-mediated immunity being principally affected by Se deficiency. Blood Se levels in chronic uraemic patients are frequently lower than in controls, and in these patients cellular immunity in generally impaired. METHODS: The present study was designed to assess the effects of Se supplementation over 6 consecutive months on immune parameters in haemodialysis (HD) patients from Rostock (Germany) and Chieti (Italy). In both cities, five patients were supplemented with Se (500 micrograms thrice weekly for 3 months, then 200 micrograms thrice weekly for the next 3 months), whereas another five patients received placebo. All Se determinations were performed in a single laboratory. RESULTS: In both cities, basic plasma Se levels were significantly lower in patients than in their corresponding normal controls. After beginning Se supplementation, plasma Se concentration promptly normalized and levelled off in the normal range throughout the study. Se administration was well tolerated by all patients, and no side-effects attributable to Se toxicity were observed. Although no major change in immunocompetent cells (white blood count, total lymphocyte count, lymphocyte subpopulations) was observed during Se therapy, an improvement in T-cell response to phytohaemoagglutinin (as evaluated in Rostock patients) and a significant progressive increase in delayed-type hypersensitivity (as evaluated in Chieti patients) was observed in supplemented patients. After 6 months of Se therapy, the increase in delayed-type hypersensitivity of supplemented patients proved to be significantly higher when compared to both presupplementation values and to the results found in non-supplemented patients. Three months after suspension of Se supplementation, plasma Se levels and delayed hypersensitivity significantly decreased in Chieti patients, with both parameters returning similar to presupplementation values. CONCLUSIONS: In accordance with previous studies done in non-uraemic subjects, our investigation demonstrates for the first time the immunostimulatory properties of Se in HD patients. Though several problems on Se metabolism in uraemia remain unresolved, in our opinion moderate and safe Se supplementation can be beneficial in chronic uraemic patients.

Adjuvants, Immunologic↗

Reduced human lymphocyte blastogenesis and enhancement of adenosine triphosphate (ATP) by L-carnitine.

Carnitine is associated with lipid synthesis and its deficiency may lead to cardiomegaly with parenchymal lipid in the heart, kidney and liver. In our study we found that pretreatment of peripheral blood mononuclear cells (PBMC) with serial dilutions of L-Carnitine (100 micrograms/ml-1 pg/ml) inhibits, in a dose-dependent manner, lymphocyte DNA synthesis stimulated with PHA (20 micrograms/ml). L-Carnitine did not have any effect on resting PBMC. The maximum inhibition was found at 10 micrograms/ml of L-Carnitine. Moreover, in a time-course study and using an enzymatic analysis (ATP monitoring reagent), L-Carnitine enhanced ATP production on PBMC treated and untreated with PHA, reaching a maximum effect at 30 min incubation. In another set of experiments PBMC were treated with L-Carnitine alone and in combination with PHA, and the percent of receptors CD3, CD4, and CD8 were calculated with flow cytometry. After the cell incubation with L-Carnitine, the percent of all receptors studied did not change compared to L-Carnitine-untreated cells (controls). These data suggest that L-Carnitine inhibits, in a dose-dependent manner, lymphocyte blastogenesis induced by PHA, probably through the enhancement of ATP synthesis, which is considered an inhibitor of phospholipase C activity and a suppressor in lymphocyte cultures.

Adenosine Triphosphate↗