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Biomedical subjects

V Mazzarella

Publications and source records attributed to V Mazzarella.

At least 37 records · Page 2Linked to original sources

Glutamate antagonist therapy reduces neurologic deficits produced by focal central nervous system ischemia.

Ischemia may increase synaptic concentrations of glutamate, which may cause neuronal damage. Drugs that antagonize glutamate's effects may reduce this type of damage. MK-801, an N-methyl-D-aspartate receptor antagonist that readily enters the central nervous system, was evaluated in two focal central nervous system ischemia models: a multiple cerebral embolic model and a rabbit spinal cord ischemia model. When animals were treated five minutes after the onset of injury, MK-801 was effective in reducing ischemic damage in both models. In the multiple cerebral embolic model, the average dose of microspheres trapped in the brain increased from 344.8 +/- 51.4 micrograms (n = 29) in controls to 534 +/- 41.4 micrograms (n = 17) in the MK-801-treated group. Similarly, in the rabbit spinal cord ischemia model, the average ischemia duration increased from 28.9 +/- 1.7 minutes (n = 52) in controls to 50.6 +/- 3.9 minutes (n = 12) in the MK-801-treated group. These results suggest that this glutamate antagonist should be useful for the treatment of stroke.

Animals↗

Tissue plasminogen activator. Reduction of neurologic damage after experimental embolic stroke.

Tissue plasminogen activator (tPA) has become available for pharmacologic use, and it appears to produce relatively fewer hemorrhagic complications than the previously available, less specific thrombolytic agents. We tested the effects of tPA in several models of embolic stroke and found that neurologic damage was reduced when the drug was administered as late as 45 minutes after cerebral embolic occlusion. The mechanism of therapeutic efficacy of tPA was probably thrombolysis. Drug-induced hemorrhages did not occur when therapy was started within four hours after the onset of vascular occlusion. These results suggest that tPA may be useful for thrombolytic therapy of embolic stroke if the drug is administered rapidly after the onset of vascular occlusion.

Animals↗

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↗

Effects of calcium channel blockers on neurologic outcome after focal ischemia in rabbits.

To determine the efficacy of calcium channel blockers in preserving neurologic function after central nervous system ischemia, we studied three such agents in two animal models. We treated rabbits after inducing ischemia in the brain with intra-arterial microspheres and in the spinal cord using a removable aortic occluding device. We found no benefit, in terms of neurologic functional outcome, from lidoflazine, nimodipine, or nicardipine. All three agents elevated regional blood flow in the spinal cord. We conclude that calcium antagonists are not likely to prove beneficial if used alone in the treatment of focal central nervous system ischemia.

Animals↗

A model for quantitative evaluation of embolic stroke therapy.

We developed a small animal embolic stroke model for pharmacological screening trials. Microspheres are injected into the carotid circulations and group embolus dose-response relationships are calculated. Emboli quantity is related to neurologic injury, and small changes in neurologic function are detectable. Rabbits tolerated twice as many microspheres when cyproheptadine-treated after embolization. This demonstrated both the sensitivity of the model and the value of serotonin antagonists in reducing neurological injury.

Animals↗

Red blood cell lipid peroxidation in predialysis chronic renal failure.

In hemodialysis patients the pentose-phosphate shunt activity is deficient. As a consequence, the lipid peroxidation of the erythrocyte membranes is increased as shown by the increase in malonyldialdehyde concentrations and is accompanied by a decrease of the level of vitamin E in RBC. In the present study we have found that increased lipid peroxidation of the erythrocyte membranes is present also in chronic renal failure patients in the predialysis state, provided that the serum creatinine levels are higher than 5 mg/dl.

Erythrocyte Membrane↗

Relationship between red blood cell lipid peroxidation, plasma hemoglobin, and red blood cell osmotic resistance before and after vitamin E supplementation in hemodialysis patients.

It has been reported that increased peroxidation of the polyunsaturated fatty acids in the erythrocyte membranes is one of the causes of chronic hemolysis in uremic patients on hemodialysis and that therapeutic doses of vitamin E are effective in reducing peroxidation, improving the hematocrit. The present study shows how the reduced peroxidation, induced by a course with therapeutic doses of vitamin E, is paralleled by a significant reduction of plasma hemoglobin concentrations at the end of the dialysis and by a significant improvement of erythrocyte osmotic resistance. The findings lead to the suggestion that the administration of tocopherol to patients on chronic hemodialysis for end-stage renal disease may be beneficial in improving anemia, acting via a reduction of lipid peroxidation of the red blood cell membranes. Whether this can reduce the need for the transfusions can be assessed only with a longitudinal long-term study, which is also necessary to determine whether the preliminary findings of this report have important clinical applications.

Adolescent↗

Red blood cell membrane lipid peroxidation in continuous ambulatory peritoneal dialysis patients.

We have recently described that in the erythrocytes from uremic patients on chronic hemodialysis, the pentose-phosphate shunt is defective, the membrane concentrations of malonyldialdehyde, resulting from peroxidation of polyunsaturated fatty acids in the membranes themselves, are increased, and the concentrations of vitamin E, an antioxidizing agent, are reduced. In the present study we have analyzed these same metabolic aspects in a group of uremic patients in continuous ambulatory peritoneal dialysis. We have found normal function of the pentose-phosphate shunt, slightly elevated concentrations of malonyldialdehyde compared to controls, but definitely lower than in chronic hemodialysis patients, and higher tocopherol concentrations than in both controls and chronic hemodialysis patients.

Adult↗

Correction of uremic acid-base imbalance in biofiltration: standardization of the amount of bicarbonate infused.

Beneficial effects of biofiltration on acid-base balance have been described, especially in patients showing poor tolerance to standard hemodialysis. This study was designed to standardize the amounts of bicarbonate to be infused for optimal control of the acid-base balance, without the adverse reactions of symptomatic metabolic alkalosis. In three adult patients (body weight greater than 55 kg) a 300 mEq. bicarbonate infusion achieved normal pre- and post-dialysis plasma levels of bicarbonate and normal pre- dialysis pH. Conversely, in three adolescent patients (body weight less than 40 kg) pre- dialysis plasma bicarbonate levels and pre- dialysis pH could not be adequately corrected in spite of increasingly high doses of bicarbonate infused up to a maximum of 240 mEq per treatment. Larger amounts brought on symptoms of metabolic alkalosis.

Acid-Base Imbalance↗

Clinical evaluation of biofiltration in uremic patients undergoing chronic hemodialysis.

The clinical efficiency of biofiltration (BF) was evaluated in six hemodialysis patients with poor clinical tolerance for standard hemodialysis. Three were adults (mean age 34 years, mean body weight 67 kg) and three adolescents (mean age 17 years, mean body weight 38 kg). Mean maintenance hemodialysis time was 90.5 months (range 49-132). BF treatments lasted three hours in all cases, for a total of nine hours weekly, with AN69 S membranes and infusion of 3 liters of HCO3 solution (100 mEq/l for the adults, 80 mEq/l for the adolescents). We recorded intra- and inter-dialytic symptoms daily, hematological values and acid-base status monthly. Multimodality evoked potentials were recorded after 3 and 9 months. Biochemical values reached a steady state 9 months from the beginning of the study, metabolic acidosis was corrected more efficiently in both groups at the end of dialysis, but only in the adult patients, were pre-dialysis plasma bicarbonates within normal limits. A clear drop in the number of episodes of intradialytic hypotension was noticed in both groups, but the adolescent patients' tolerance for dialysis did not improve. In conclusion our data show that in adult patients with poor tolerance BF offers a dependable alternative to standard hemodialysis, and the length of treatment can be reduced.

Acid-Base Equilibrium↗

Pentose-phosphate shunt activity and red blood cell malonyldialdehyde levels in haemodialysis and in CAPD patients.

The baseline concentrations of MDA in the RBC membranes and the MDA production in the erythrocytes following stimulation with ascorbate and cyanide are compared in a group of uraemic patients on chronic haemodialysis and in one treated with CAPD. Lower baseline concentrations and smaller production of MDA following in vitro stimulation, point to a better function of the pentose-phosphate shunt in CAPD patients than in haemodialysis.

Adolescent↗

Red blood cell membrane lipid peroxidation and chronic haemolysis in haemodialysis patients.

Pre dialysis concentrations of malonyldialdehyde (MDA) in the red blood cell membranes and pre and post dialysis percent variation of plasma haemoglobin levels are studied in a group of uraemic patients on maintenance haemodialysis both before and after a therapeutic trial with vitamin E. The findings show a significant correlation between MDA levels and percent variation of plasma haemoglobin during dialysis, thus indicating that reducing the amount of lipid peroxidation can help to reduce intradialytic chronic haemolysis.

Adolescent↗

Leukopenia, hypoxemia, and complement activation during a single hemoperfusion.

White blood cell count, acid-base balance, PO2, and complement function in five uremic patients undergoing a single hemoperfusion employing activated charcoal coated with methacrylate were studied. After 20 min on hemoperfusion, a marked leukopenia [ranging from 6,080 +/- 526 to 3,740 +/- 1,124 (p less than 0.02)] and hypoxemia [ranging from 106 +/- 13.8 to 80.2 +/- 11.9 mm Hg (p less than 0.02)] were observed. At the same time, total hemolytic complement decreased from 135 +/- 15.7 to 123 +/- 14.7 U/ml (p less than 0.001) and alternative pathway activity from 38.1 +/- 5.1 to 33.1 +/- 6.7 U/ml (p less than 0.005). C3 and B cleavage fragments were detected in the samples tested, thus demonstrating the activation of the complement alternative pathway. After 60 min, the different parameters tended to increase but did not reach the baseline levels. A direct correlation between the degree of leukopenia and the reduction of PO2 throughout the hemoperfusion period was found. pH PCO2, and HCO-3 did not change throughout the hemoperfusion period. The results demonstrate that complement activation, leukopenia, and hypoxemia occur during hemoperfusion.

Acid-Base Equilibrium↗

Evaluation of acid-base balance and pO2 with acetate dialysis in non-uremic patients.

The aim of our work was to evaluate the immediate effects of acetate-dialysis in patients with normal renal and respiratory function. For this purpose pH, pO2, pCO2 and HCO3- were monitored in arterial blood before dialysis, after 60, 120, 180 mns and at the end of each treatment in two groups of patients on chronic hemodialysis, a first group of schizophrenic patients and a second group of uremic patients. In the first group of patients the predialytic values were in the normal range. After hemodialysis HCO3- and pCO2 significantly decreased, both these changes were associated with a stable pH. The pO2 significantly decreased after 60 mns of dialysis. At the end of dialysis the pO2 increased without significant variation compared to predialytic values. In conclusion in non-uremic hemodialysis patients metabolic acidosis due to the loss of bicarbonate through the membrane is compensated by respiratory alkalosis. This respiratory alkalosis is not due to hypoventilation secondary to respiratory centre inhibition, but is mainly due to the pCO2 loss through the dialysis membranes.

Acetates↗