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Biomedical subjects

M Taccone-Gallucci

Publications and source records attributed to M Taccone-Gallucci.

At least 19 recordsLinked to original sources

N-3 PUFAs reduce oxidative stress in ESRD patients on maintenance HD by inhibiting 5-lipoxygenase activity.

Reactive oxygen species formation and release of pro-inflammatory/pro-atherogenic cytokines, that is, interleukin 1-beta and tumor necrosis factor-alpha, need the activation of the arachidonic acid cascade via the enzyme 5-lipoxygenase (5-Lox). 5-Lox activity and expression are significantly increased in peripheral blood mononuclear cells (PBMCs) of end-stage renal disease (ESRD) patients on maintenance hemodialysis (HD). Diets enriched with n-3 polyunsaturated fatty acids (PUFAs) (omega-3) have been associated to a lower incidence of coronary heart disease (CHD) and a reduction in atherosclerotic lesions. Omega-3 may interfere with the arachidonic acid cascade by inhibiting 5-Lox. Lipid peroxidation, leukotriene B(4) (LTB(4)) production, 5-Lox activity and expression were investigated in PBMC isolated from ESRD patients under maintenance HD before and after a 3-month oral supplementation with omega-3 at a daily dose of 2700 mg of n-3 PUFAs at the average eicosapentaenoic acid/docosaesaenoic acid ratio of 1.2 and finally after a further 3-month washout with no omega-3 supplementation. PBMCs from non-uremic volunteers were also investigated for comparison to normal parameters. Administration of omega-3 reduced significantly lipid peroxidation (P < 0.0001), LTB(4) synthesis (P < 0.0001) and 5-Lox activity (P < 0.0001), with no effect on 5-Lox protein expression. After the 3-month washout, all parameters were comparable to those observed before treatment. Our results resemble those obtained after oral administration of vitamin E and are consistent with a reversible, dose-dependent inhibition of 5-Lox by omega-3. Upregulation of 5-Lox may also be related to the increased mitochondrial damage and apoptosis of PBMCs observed in ESRD patients compared to non-uremic controls. Omega-3 may thus protect PBMCs of ESRD patients against oxidative stress.

Aged↗

Vitamin E suppresses 5-lipoxygenase-mediated oxidative stress in peripheral blood mononuclear cells of hemodialysis patients regardless of administration route.

A number of pathological conditions caused by oxidative stress have been reported in uremic patients undergoing maintenance hemodialysis (HD). Enhanced lipid peroxidation was previously observed in peripheral blood mononuclear cells (PBMCs) of HD patients. Upregulation of 5-lipoxygenase (5-Lox) activity and protein content with enhanced production of leukotriene B(4) (LTB(4)) and membrane lipoperoxides was also shown in PBMCs of HD patients. Administration of free vitamin E specifically inhibited 5-Lox activity without affecting gene expression at the protein level. To assess whether oral or intramuscular (IM) administration of vitamin E may suppress 5-Lox in HD patients, PBMCs from 16 subjects on maintenance HD therapy for at least 6 months were investigated before and after a short course of IM or oral administration of vitamin E (8 patients per group). PBMCs from 13 healthy controls were also evaluated and assumed as the reference standard. Vitamin E significantly reduced lipid peroxidation, LTB(4) content, and 5-Lox activity in PBMCs, whereas 5-Lox gene expression at the protein level was not affected. There were no significant differences in these parameters between patients treated with IM or oral vitamin E. PBMCs of HD patients showed enhanced membrane lipid peroxidation and release of LTB(4), both linked to upregulation of 5-LOX: 5-Lox activity and related oxidative stress were significantly (although not completely) suppressed by vitamin E regardless of the administration route.

Administration, Oral↗

Activation of 5-lipoxygenase and related cell membrane lipoperoxidation in hemodialysis patients.

Lipid peroxidation was shown at the membrane level in peripheral blood cells of patients hemodialyzed on cuprophan dialyzers, and was mainly attributable to the generation of conjugated hydroperoxides in the lipid bilayer. The oxidative index (i.e., the A234/205 ratio) of membrane lipids was 3.2-fold higher in hemodialysis patients than in healthy control subjects, and also the level of leukotriene B4 was significantly increased (up to 1.7-fold over control). Both membrane peroxidation and release of leukotriene B4 were linked to upregulation of 5-lipoxygenase activity (up to 2.4-fold over control) and expression at the protein level (up to 1.9-fold). Vitamin E, the most important lipophilic antioxidant, prevented both membrane peroxidation and release of leukotriene B4 by inhibiting 5-lipoxygenase activity without affecting enzyme expression. Similar results were observed in patients hemodialyzed on polymethylmetacrylate membranes, but in this case the activation of 5-lipoxygenase was less pronounced. The use of a purified 5-lipoxygenase demonstrated that vitamin E was a reversible inhibitor of enzyme activity (IC50 = 35 +/- 4 microM), further characterized as noncompetitive (Ki = 30 +/- 3 microM). Taken together, the results reported here shed some light on the mechanism responsible for the oxidative damage in hemodialysis. Moreover, the beneficial effect of vitamin E described here may have relevance for the therapy of patients with kidney disease.

Arachidonate 5-Lipoxygenase↗

Cardiac function and oxygen balance in septic patients during continuous hemofiltration.

The aim of this work was to study hemodynamic, oximetric and metabolic parameters in septic patients during continuous hemofiltration, in order to determine whether the changes in hemodynamic parameters can influence the oxygen utilization in peripheral tissues. 29 multiple organ failure patients with septic shock were studied during the first 48 h of continuous hemofiltration: 18 were submitted to CAVH and 11 patients were treated with CAVHD to correct ARF and fluid overload. Our data show that RVEF improves and REDVI reduces progressively during treatment, together with a significant reduction of the cardiac index after 48 h of CAVH(D). There were no significant variations in oxygen tissue parameters, while plasma lactate was reduced significantly. In conclusion, our data confirm that continuous hemofiltration may be useful in septic patients to correct fluid overload and ARF, without affecting hemodynamic stability and oxygen balance. Moreover, in septic patients, this technique improves hemodynamics, reduces the filling pressure in the right heart and reduces hyperdynamic response as CI and SVRI, without any negative effects on O2 balance.

Adult↗

Blood purification procedures for acute renal failure: convenient strategy related to clinical conditions.

The choice in the renal replacement therapy of acute renal failure (ARF) should match the patients' individual needs and the characteristics of available therapies. 141 ARF patients, 65 with "isolated' ARF (group I) and 76 with ARF in multiorgan failure (group II), have been treated. In 33 patients of group I standard bicarbonate hemodialysis was used, while acetate-free biofiltration was used for the others. In group II, 42 patients have been treated by continuous arteriovenous hemofiltration and 34 patients by daily recycled bicarbonate hemodialysis. Our data show that acetate-free biofiltration and bicarbonate dialysis were both highly dependable, but acetate-free biofiltration was better tolerated. Continuous arteriovenous hemofiltration is the method of choice in high-risk patients; daily bicarbonate hemodialysis is preferable only in patients with hemorrhagic diathesis. The average survival time is 55.2% with a statistically significant difference between groups I and II, while no difference has been observed within the same group according to the procedure.

Acute Kidney Injury↗

Acetate-free biofiltration in acute renal failure.

Hemodialysis treatment for acute renal failure is associated with a high incidence of adverse reactions. Hemodynamic stability and adequate correction of acid-base and hydroelectrolyte imbalance are the main goals of dialytic strategy in acute renal failure. However, the variety of etiology and the diversity of clinical conditions suggest that individualized treatment may be advisable. To this purpose, in 26 patients suffering from "isolated" acute renal failure of different etiologies, we have used acetate-free biofiltration. We have performed 411 dialyses with an extremely low incidence of symptomatic treatments and remarkable cardiovascular stability. Correction of fluid, electrolyte, and acid-base imbalance proved excellent. Dialytic efficacy proved adequate. Our data show that acetate-free biofiltration is an easy technique suitable for individualized treatment and adaptable to changing needs during hemodialysis in patients with isolated acute renal failure.

Acetates↗

Oxygen tension monitoring in uremic patients during hemodialysis treatment.

The aim of this study was to evaluate the influence on cerebral and cutaneous vascular regions of PaO2 reduction during acetate dialysis, by monitoring conjunctival oxygen tension (PcjO2) and transcutaneous oxygen tension (PtcO2) during hemodialysis (HD) treatment. The study was performed on 23 patients with end-stage renal disease in chronic HD. All patients underwent dialytic treatment with cuprophan membranes and acetate containing dialysate. PcjO2 and PtcO2 were recorded and PaO2 and arterial carbon dioxide tension (PaCO2) were also measured. Results of the study show that hypoxemia during acetate dialysis with cuprophan membranes is not accompanied by changes of PcjO2 and therefore by changes in cerebral oxygenation. Moreover, PtcO2 remains constant during dialysis treatment. Furthermore, maintenance of normal oxygen tension at the conjunctival level is not obtained at the expense of the peripheral region of the skin.

Adult↗

Platelet lipid peroxidation in haemodialysis patients: effects of vitamin E supplementation.

In haemodialysis patients, increased concentrations of malonyldialdehyde and decreased vitamin E content indicate lipid peroxidation in the platelets from oxidative damage. The same process has been described in red blood cells and in mononuclear cells in peripheral blood. However, platelet aggregation is within normal limits and does not change after treatment with vitamin E. On the other hand vitamin E supplementation reverts completely the biochemical abnormality of the platelets.

Blood Platelets↗

Lack of oxidative damage in serum polyunsaturated fatty acids before and after dialysis in chronic uremic patients.

We described previously that in the erythrocytes and mononuclear blood cells from uremic patients on chronic hemodialysis, the membrane concentrations of malonyldialdehyde (MDA), resulting from peroxidation of polyunsaturated fatty acids (PUFA) in the membrane itself increased, and the concentrations of vitamin E (VIT E), the major antioxidizing agent, were lower. In the present study we analysed whether similar oxidative damage is seen in the serum from hemodialysis patients and whether the serum fatty acid pattern is affected. No evidence was found of oxidative damage in the serum during hemodialysis, serum concentrations of MDA and VIT E remaining constant before and after dialysis. No change was observed in serum pattern of PUFA, particularly linoleic acid. We therefore assume that the oxidative damage described in uremic patients is mainly intracellular.

Adult↗

Discrepancies between serum and erythrocyte concentrations of vitamin E in hemodialysis patients: role of HDL-bound fraction of vitamin E.

Recently, we have demonstrated that hemodialysis (HD) patients have higher serum and lower erythrocyte concentrations of vitamin E than controls. It is known that transfer of vitamin E from serum to erythrocyte is mostly due to high-density lipoproteins (HDL). For a better definition of the pattern of distribution of vitamin E in HD patients, we have dosed the amount of vitamin bound to serum HDL fraction. In 8 patients and in 8 healthy controls, we have determined the concentration of serum erythrocyte and HDL-bound vitamin E. The latest was obtained on an ultracentrifuged HDL fraction. HDL fractions from HD patients have been found to contain larger amounts of vitamin E than controls. The previously described higher serum and lower erythrocyte concentrations of vitamin E in HD patients have been confirmed in the study. The deficit of vitamin E in the membranes of erythrocytes from HD patients has been shown to be the result of increased consumption of the vitamin in the erythrocyte membranes, where it represents the major antioxidant agent. However, the finding of increased amounts of vitamin bound to HDL in HD patients suggests that the transfer of the vitamin to the erythrocyte membranes may also be defective.

Adult↗