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Biomedical subjects

M Morosetti

Publications and source records attributed to M Morosetti.

47 records · Page 3Linked to original sources
PubMedDate not supplied

Disappearance of oxidative damage to red blood cell membranes in uremic patients following renal transplant.

Hemodialysis patients display increased oxidative damage to red blood cell (RBC) membranes, characterized by elevated levels of malonyldialdehyde (MDA), a short chain aldehyde produced by the oxidation of the polyunsaturated fatty acids (PUFA) in the RBC membranes. This is the result of a metabolic blockage of the pentose-phosphate shunt in uremic patients, which causes reduced detoxification of highly oxidative free radicals. The oxidative damage induces increased RBC rigidity and decreased RBC deformability, therefore favoring hemolysis. The aim of this work was to determine if a functioning renal graft would restore normal erythrocyte metabolism, reducing the oxidative damage. To this end, we have determined RBC MDA concentrations in 20 hemodialysis (HD) patients (RBC MDA 18.22 +/- 4.36 micrograms/ml packed RBC), 20 renal transplant (T) patients with well functioning grafts (serum creatinine less than 2 mg%) (RBC MDA 1.2 +/- 0.4 micrograms/ml packed RBC) (T vs. HD P less than 0.005) and 20 healthy controls (HC) (RBC MDA 1.44 +/- 0.6 micrograms/ml packed RBC) (HC vs. HD P less than 0.005; HC vs. T NS). Our findings show that a well-functioning renal graft restores normal RBC metabolism and eliminates the oxidative damage induced by uremia.

Adolescent↗
PubMedDate not supplied

Plasmapheresis versus plasma perfusion in acute Guillain-Barré syndrome.

Guillain-Barré Syndrome (GBS) is an acute post infectious or disimmune illness that affects nerve roots and peripheral nerves. Multicenter studies have clearly shown that plasma exchange (PE) provides valuable amelioration of GBS. It was recently suggested that plasma perfusion (PP) on phenylalanine columns displays the same therapeutic effects of PE in neuroimmunologic disorders, without the infectious risks linked with plasma replacement. In this study, the authors compared the efficacy of PE versus that of PP in two groups of patients suffering from GBS by investigating the clinical outcomes and the electrophysiologic and cerebrospinal fluid findings. Of 22 patients suffering from GBS, 16 underwent seven sessions of PE in a mean time of 15 days (Group A). Six patients, showing the same clinical pattern, underwent three sessions of PP in a mean time of 10 days (Group B). Data reported in Group A show that PE: 1) stops the progressive worsening of the disease, 2) prevents the development of acute respiratory failure, 3) allows an early and significant clinical improvement with change in disability grade, and 4) improves motor conduction velocities and motor action potentials when recorded 45 days after the end of treatment. Data in Group B show that PP allows a slower and later improvement in disability grade, and electrophysiologic data recorded at the end of treatment was worse after 45 days. Finally, it may be concluded that PE has beneficial effects on GBS in terms of time of recovery, complication rate, and relapses. Plasma perfusion did not show the same results.

Acute Disease↗
PubMedDate not supplied

Oxidative damage to RBC membranes and pentose phosphate shunt activity in hemodialysis patients after suspension of erythropoietin treatment.

During follow-up of anemic hemodialysis patients (HDP) treated with recombinant human erythropoietin (rHuEpo), it was noticed that in five HDP, some time after suspension of rHuEpo, hemoglobin (Hb) levels remained at acceptable levels. A metabolic block of the pentose phosphate shunt (PPS) has been described in HDP, which leads to increased oxidative damage of red blood cell (RBC) membranes and increased susceptibility to hemolysis. The increased production of short-chain fatty aldehydes, including malonyldialdehyde (MDA), is an appropriate index of oxidative damage. This study aimed to verify whether the maintenance of acceptable levels of Hb was related to a change in RBC membrane oxidative damage and pentose phosphate shunt activity. In the five HDP in question who required rHuEpo (150 U/kg/week) for severe anemia (Hb = 7.48 +/- 0.95 g/dl), after a stable level of Hb > 10 g/dl was reached for at least 1 month, rHuEpo treatment was stopped. Hb levels remained adequate (Hb = 10.68 +/- 0.77 g/dl) after 14.6 +/- 7.64 months. The oxidative damage was evaluated by measuring RBC MDA (microgram/ml packed RBC) basal levels, and PPS activity by measuring MDA levels after incubation with ascorbate and cyanide (delta % RBC MDA production). Ten anemic HDP not treated with rHuEpo were used as controls (Hb = 8.12 +/- 1.32 g/dl). It was found that the maintenance of adequate levels of serum Hb after suspension of rHuEpo therapy is related to a decrease in RBC membrane oxidative damage (RBC MDA HDP = 2.40 +/- 0.41 vs. RBC MDA controls = 18.23 +/- 6.56; P < 0.005) in consequence of the normalization of pentose phosphate shunt activity.

Aged↗
PubMedDate not supplied

Administration of GSH has no influence on the RBC membrane: oxidative damage to patients on hemodialysis.

In patients on hemodialysis, a metabolic block of the pentose phosphate shunt has been described that impairs the reduction of oxidized glutathione. The block results in lack of detoxication of the free hydroxyl radicals produced inside the red blood cell (RBC) and causes oxidative damage to the polyunsaturated fatty acids of the RBC membrane that results in formation of aldehydes. Malonyldialdehyde has been used as an index of the oxidative damage. In a study group of 13 patients on hemodialysis, the authors have tested whether administering reduced glutathione (GSH) at 1200 mg/day for 1 month could minimize oxidative damage to the RBC membranes and improve the hematologic parameters. Treatment with GSH was followed by significant improvement of hematocrit (P = 0.008), hemoglobin (P = 0.03), and RBC count (P = 0.0037); however, oxidative damage to the membranes was increased (P = 0.0004), which suggests that improvement of the hematologic parameters is not related to reduction of the oxidative damage. This is because oxidized glutathione, formed in the oxidative process, cannot be reduced back to GSH because of alteration of the pentose phosphate shunt.

Adult↗
PubMedDate not supplied

[Italian study on the treatment of anaemia in chronic dialysis patients switched over to less frequent doses of darbepoetin from human recombinant erythropoietin (rHuEPO)].

BACKGROUND: Darbepoetin alpha is a novel erythropoiesis stimulating protein with unique properties as compared to recombinant human erythropoietin (rHuEPO), including a three-fold longer elimination half-life that allows for less frequent dosing. This study was aimed at testing the efficacy and safety of darbepoetin alpha in a large number of chronic dialysis patients switched from rHuEPO. METHODS: Nine hundred and fifty dialysis patients in stable treatment with rHuEPO were switched to darbepoetin alpha. Patients receiving rHuEPO 2 or 3 times weekly were switched to once weekly darbepoetin alpha and those receiving rHuEPO once weekly were switched to once every other week darbepoetin alpha. Patients received darbepoetin alpha by the same route of administration (SC or IV) as the one used for rHuEPO. The unit doses of darbepoetin alpha (10-150 microg) were titrated to maintain haemoglobin concentration within -1.0 and +1.5 g/dL of the individual mean baseline haemoglobin levels and between 10 and 13 g/dL for 24 weeks. RESULTS: The mean change in haemoglobin from baseline to the evaluation period (weeks 21-24) was statistically but not clinically significant [-0.10 g/dL (95% CI: -0.18, -0.02]. In general, the geometric mean weekly dose of study drug from screening/baseline to evaluation period remained substantially unmodified [(from 26.10 micro g/wk to 25.90 microg/wk; percentage change -0.40% (95% CI: -3.78, 3.10)]. Overall, darbepoetin alpha was well tolerated. CONCLUSIONS: The treatment of anaemia of a large dialysis patient population with unit dosing of darbepoetin alpha is effective and safe in maintaining target haemoglobin concentration at reduced dose frequency.

Anemia↗
PubMedDate not supplied

[Clinical experience in HFR with a new resin-only sorbent cartridge].

Adsorbent therapies have become increasingly popular over the last several years as they permit an additional method to selectively or non-selectively remove toxins. Adsorbents offer a unique removal strategy as they have an extremely high adsorption capacity due to their great surface area. This paper describes experiments that utilized a synthetic divinylbenzene styrenic resin cartridge to remove uremic toxins from chronic renal failure patients. The resin-only cartridge was tested as an alternative after a small number of patients (primarily taking ACE inhibitors) experienced gastrointestinal problems using hemodiafiltration with on-line regeneration (HFR). Subsequent laboratory evidence suggested that the particular carbon used in the cartridge was able to activate contact phase activation. This could potentially cause problems in patients taking ACE inhibitors, as they are unable to degrade bradykinin efficiently. The resin-only cartridge was tested in at 6 centers throughout Italy and included patients that had experienced previous reactions to the carbon-resin cartridge. At the conclusion of the study, no adverse reactions were reported and the cartridge exhibited excellent removal of b2 microglobulin and angiogenin.

Adult↗
PubMedDate not supplied

Vitamin E supplementation and oxidative status of peripheral blood mononuclear cells and lymphocyte subsets in hemodialysis patients.

Increased oxidative damage to cell membrane constituents causes profound changes in the membrane cytoarchitecture and modifications of the membrane physiological properties, e.g., the ability to respond to hormonal stimuli. In uremic patients receiving intermittent hemodialysis, a metabolic block of the phosphate pentose shunt has been described. This leads to insufficient detoxication of the hydroxyl radicals formed within the cells and therefore to increased oxidative damage to the polyunsaturated fatty acid constituents of the cell membranes. Vitamin E is known to reduce this oxidative damage and its harmful effects. We studied vitamin E (alpha-tocopherol acetate) administration in 10 chronically uremic patients receiving intermittent hemodialysis for positive effects on cell membrane-receptor response. The patients were studied before and after treatment for the extent of oxidative damage in peripheral mononuclear cells and for response to monoclonal antibodies to specific markers of T-lymphocyte subsets. After vitamin E treatment, oxidative damage decreased, and the membranes of peripheral mononuclear cells contained greater amounts of some unsaturated fatty acids. This is in agreement with a modification of the membrane phenotype markers of T-lymphocyte subsets and seems to confirm in vivo that changes in membrane structure first induced by increased oxidative damage due to the blockage of the phosphate pentose shunt can be reduced by the antioxidant action of vitamin E, which significantly influences the expression of membrane determinants.

Adult↗
PubMedDate not supplied

[Evaluation of cognitive functions in patients with chronic renal insufficiency].

Fifteen undialyzed and thirteen dialyzed patients affected by chronic renal failure were studied by means of an extensive neuropsychological battery with the aim of assessing the incidence of a deterioration of cognitive functions. Mean performances scores obtained by the two groups of patients were compared with analogous scores obtained by a group of control subjects similar as for literacy and age. The comparisons among the three groups did not reveal any difference as for performance scores obtained to various tasks nor for the global assessment derived for the entire battery. Furthermore our data do not point out any significative correlation between global performances on neuropsychological battery and blood levels of creatinine and urea nitrogen or duration of dialytic treatment of renal subjects. In conclusion, the results of our study do not show evidence of cognitive impairment in subjects affected by chronic renal failure and do not confirm the hypothesis of a detrimental effect of prolonged periods of dialytic treatment on cognitive functions.

Blood Urea Nitrogen↗
PubMedDate not supplied

Haematological changes induced by direct contact over a coated activated charcoal: in vivo and in vitro study.

In evaluating biocompatibility, haematological changes induced by ACCM in vivo and in vitro were studied. Twenty minutes after the start of haemoperfusion a significant fall in white blood cell number was found. After 60 minutes the leucopenia still occurred. In a previous work we suggested that complement activation is at least one of the possible mechanisms responsible for these phenomena. Moreover, our data showed a significant decrease in platelet number after 60 minutes of haemoperfusion. During the in vitro study, we found, using citrated blood, a significant correlation between aggregation response to ADP and collagen, either at different ACCM doses or at various periods of incubation. Our results suggest that the fall in platelets is due to platelet aggregation. The haemocoagulation study may have clinical importance in high-risk patients when haemoperfusion is required.

Adenosine Diphosphate↗
PubMedDate not supplied

The treatment of severe forms of myasthenia gravis.

In this study we introduced and tested the clinical efficacy of a combined treatment based on the association of plasma exchange (PE) with high daily doses of prednisone in 18 patients with severe forms of myasthenia gravis (MG). A myasthenic score based on strength and resistance was evaluated in each patient in basal condition and during the treatment. The study design included 5 sessions of PE, performed within a period of 15 days, 1 session every 3 days, associated with administration of oral prednisone (1 mg/kg of body weight), which began at the same time as the first session and was continued following a daily schedule for at least three months. A significant improvement was obtained from the start of the therapy, with a reduction of the myasthenic score from 26.56 to 11.44 by day 10 and with further reduction after PE interruption. An early improvement, recorded within 24-48 hours of the beginning of the study design, was observed in 11/18. The administration of steroid therapy was never followed by a worsening of myasthenic symptoms (as reported when it is administered in the absence of concomitant PE). No recurrence of symptoms was reported after 29 months' follow-up. This type of therapeutic association was generally well tolerated and no unwanted side effects were observed. According to our results we can conclude that medium-high doses of oral prednisone in simultaneous association with PE lead to a successful control of severe forms of MG and may be considered a valid therapeutic strategy.

Adolescent↗