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Biomedical subjects

O Mannarino

Publications and source records attributed to O Mannarino.

15 recordsLinked to original sources

Morphological and molecular assessment of apoptotic mechanisms in peripheral neuroblastic tumours.

Multiple defects in apoptotic pathways have been described in peripheral neuroblastic tumours (NTs). Mitosis-karyorrhexis index (MKI) is a reliable morphological marker identifying favourable and unfavourable NTs. The extent to which apoptotic processes contribute to determine the clinical significance of MKI is still undefined. Apoptosis was investigated in a series of 110 peripheral NTs by comparing MKI to immunohistochemical and molecular apoptotic features. High MKI was found in 55 out of 110 NTs (50%) and was associated with advanced stage (P = 0.007), neuroblastoma (NB) histological category (P = 0.024), MYCN amplification (P < 0.001), and poor outcome (P = 0.011). Overall survival probability was 45% in patients with high MKI compared to 73% in patients with low MKI. In the same 110 NTs, the expression of Bcl-2, Bcl-XL, Bax and Mcl-1 was studied by immunohistochemistry, but no significant associations were found with clinicohistological features. Microarray analysis of apoptotic genes was performed in 40 out of 110 representative tumours. No significant association was found between the expression of apoptotic genes and MKI or clinicohistological features. Proliferative activity was assessed in 60 out of 110 representative tumours using Ki67 immunostaining, but no significant correlations with MKI or clinicobiological features were found. In NTs, the combination of apoptosis and proliferation as expressed by MKI is a significant prognostic parameter, although neither of them is per se indicative of the clinicobiological behaviour and outcome.

Adolescent↗

Usefulness of cyanide-nitroprusside test in detecting incomplete recessive heterozygotes for cystinuria: a standardized dilution procedure.

We present the results of a cyanide-nitroprusside test (CNT) after a standardized dilution procedure of urine samples and report the efficiency of this method in detecting heterozygotes for cystinuria when applied on an open pediatric population. In the preliminary study we assayed by quantitative determination of amino acids 162 urine samples from a hospital population identifying 24 type III heterozygotes and 2 type II heterozygotes for cystinuria. The classic CNT gave 38 false positive results and 5 false negative results showing a sensitivity and specificity of 0.808 and 0.721, respectively. When progressively diluted, all samples of heterozygotes remained CNT positive up to a creatinine concentration of 90 mg/dl. At this level of dilution 31 out of 38 false positive turned to negative, thus obtaining a specificity of 0.922 without a lowering of the sensitivity in detecting heterozygotes. The standardized dilution at 90 mg/dl of creatinine concentration was applied to 74.7% of a population of 1024 schoolchildren. In this way 163 out of 210 positive results were eliminated and thus the specificity of CNT rose from 0.789 to 0.953. On the basis of these results, the method proposed can be regarded as reliable and useful for a screening program in detecting heterozygotes for cystinuria.

Adolescent↗

[Evaluation of N-acetyl-beta glucosaminidase in upper and lower urinary tract infections in childhood. Clinical study of 168 children].

BACKGROUND: Urinary N-acetyl-beta-glucosaminidase (NAG) is a renal tubular enzyme that may be used as a marker of tubular damage. METHODS: We studied 96 patients 1 to 8 years old and considered NAG excretion to distinguish cystitis from pyelonephritis. Whenever urinary NAG values were expressed in relation to urinary creatinine concentration and compared with urinary NAG values in 72 normal controls 1 to 14 years old grouped by age. RESULTS: Our results demonstrate that urinary NAG levels are elevated in children with pyelonephritis in the presence or absence of urinary tract abnormality. CONCLUSIONS: Therefore, we conclude that NAG may be considered as a further criteria in the diagnosis of upper urinary tract infection and interstitial tubular damage.

Acetylglucosaminidase↗

[Intestinal absorption of vitamin E in children with atrophy of the jejunal mucosa].

The intestinal absorption of vitamin E is often thought to be closely correlated to that of fatty acids, but the biochemical mechanisms involved in the process are still not clear. For this reason, the present study aimed to assess the absorption of triglycerides and vitamin E, following oral administration, in 11 children with suspected malabsorption syndromes. Intestinal biopsy in 9 children showed the presence of a flat mucosa, whereas no changes were present in 2 patients. The results confirm the inverse correlation between the absorption of triglycerides and vitamin E, as if tocopherols used an independent system of transport. These findings contrast with those reported in the literature perhaps due to the low level of precision of colorimetric techniques previously used to assay vitamin E.

Atrophy↗

Erythrocyte membrane lipid peroxidation before and after vitamin E supplementation in children with cholestasis.

In 10 children with chronic cholestasis and without neurologic signs, we evaluated lipid peroxidation and vitamin E levels in serum and in the erythrocytes before and after a therapeutic trial with alpha-tocopherol. We also studied the effects of vitamin E administration on hematocrit and hemoglobin values and on reticulocyte and erythrocyte counts. Plasma and erythrocyte malonyldialdehyde (MDA) values were significantly higher compared with normal control values, whereas plasma and erythrocyte tocopherol measurements were lower. Oral administration of high doses of vitamin E (300 mg/day for 15 days) resulted in lower serum MDA levels, whereas serum vitamin levels did not change significantly. In erythrocytes, the MDA decreased but not to control levels, and vitamin E increased but to lower values than normal. Hematologic values also improved. We conclude that longer treatment might be necessary to completely reverse the oxidative damage associated with vitamin E deficiency in children with cholestasis.

Biliary Atresia↗

[Peroxidation of erythrocyte lipids and levels of vitamin E in red blood cells in children with chronic renal insufficiency].

The tocopherol and malonyldialdeyde levels in the erythrocytes of 15 children affected by chronic renal failure, free of therapy, have been studied. Decreased levels of the former and increased of the latter were found. These data indicate red blood cell lipids peroxidation, responsible, at least in part, of the reduced red blood cell survival and of chronic anemia.

Child↗

[Sensitivity to antibiotic drugs of isolated bacteria in urinary infections in children].

The need for an early start to antibiotic therapy during infections of the urinary ways in paediatrics, even before knowing the infecting strain and chemosensitivity tests, often makes it difficult to choose the drug to be used. The present study examines all the urine samples reaching the Microbiology Laboratory of Rome University's Paediatrics Clinic between 1986 and 1988, highlighting infecting species and respective chemosensitivity. The samples were also distinguished on the basis of sex and origin (hospitalised patients and out-patients). From the data so examined it was noted that some antibiotics give a broader cover against the species most frequently encountered during urinary way infections.

Adolescent↗

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↗

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↗

Biochemical and clinical effects of vitamin E administration in homozygous beta-thalassemia.

In beta-thalassemic homozygotes, low plasma levels of tocopherols may induce a red blood cell (RBC) lipid peroxidation and consequent hemolysis. This is an indication to treat these patients with vitamin E. In this study 26 beta-thalassemic homozygotes aged 2-14 years, were given vitamin E, 10 orally and 16 parenterally, 300 mg per day for 15 days. Prior to administration and blood transfusion, as compared to normal subjects of the same age, plasma and RBC tocopherols were significantly lower, whereas RBC malonyldialdehyde (MDA) was significantly increased. In both groups, after tocopherol administration, an increase in plasma and RBC tocopherols and a decrease in RBC MDA were found. The significance of these variations was greater in the parenterally treated group than in orally treated group. The treatment with vitamin E, appears to be effective to reduce the RBC oxidative damage in homozygous beta-thalassemia, principally when administered parenterally perhaps because of its poor intestinal absorption in these subjects.

Adolescent↗

Effects of alpha-tocopherol administration on red blood cell membrane lipid peroxidation in hemodialysis patients.

The result of vitamin E treatment in 19 uremic patients in chronic hemodialysis is evaluated. In particular, the levels of erythrocyte malonyldialdehyde (MDA) and vitamin E were determined, and the fatty acid composition of red blood cell (RBC) membrane before and after treatment with parenterally administered vitamin E. A decrease of RBC MDA levels, an increase of RBC vitamin E concentrations, and a decreased saturated fatty acid to unsaturated fatty acid ratio were found after treatment with vitamin E. There was a statistically significant increase of the packed RBC volume.

Adolescent↗

Serum lipid pattern in beta-thalassaemia.

Serum lipids, phospholipid fractions and the composition of serum lipid fatty acids were studied in 20 children presenting beta-thalassaemia major, 20 heterozygous children and 20 normal controls. Total serum phospholipids, their fractions and cholesterol were significantly lower in patients with thalassaemia major. These changes were referred to hepatic damage and to severe anaemia, respectively. Some serum lipid polyunsaturated fatty acids were significantly decreased in patients with thalassaemia major as compared to heterozygotes and normal controls. Since these alterations are a sign of lipid oxidation, the causes of this phenomenon are discussed.

Child↗

Renal tubular damage in fetuses with intrauterine growth retardation.

Fetal hypoxemia is one of the most frequent causes of intrauterine growth retardation (IUGR). In chronic fetal hypoxia, peripheral blood flow and blood flow to the kidneys is reduced to maintain heart, brain and adrenal perfusion, the 'brain-sparing effect'. In kidneys the cells of the proximal tubules seem to be most sensitive to hypoxia caused by reduced blood flow. Damage to the cells of the proximal tubules can be easily diagnosed by urinary levels of N-acetyl-beta-D-glucosaminidase (NAG), an enzyme present in high concentrations in these cells. The aim of the present study was to define the levels of NAG in the amniotic fluid, to diagnose damage to the cells of the proximal renal tubules in fetuses, and to correlate them with a detectable brain-sparing effect. The study was conducted on a total of 55 pregnancies: 9 pregnancies were complicated by IUGR, and the remaining 46 normal pregnancies formed the control group. Higher levels of NAG were detected in the amniotic fluid from the IUGR-complicated pregnancies (p < 0.025). In particular, fetuses with IUGR had high levels of NAG in the amniotic fluid in 8 of 9 cases (+ 2 SD compared with controls), while 1 had normal concentrations. In the 8 cases with high concentrations of NAG in the amniotic fluid, velocimetric Doppler study documented a brain-sparing effect, which was not present in the 1 fetus with normal NAG levels. In conclusion, high levels of NAG in the amniotic fluid may identify in uterus fetuses with renal damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylglucosaminidase↗

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↗