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E Cardaioli

Publications and source records attributed to E Cardaioli.

13 recordsLinked to original sources
PubMed2004

Mitochondrial abnormalities in genetically assessed oculopharyngeal muscular dystrophy.

We report a family with a clinical diagnosis of oculopharyngeal muscular dystrophy in which muscle biopsy showed mitochondrial changes such as cytochrome-c-oxidase-negative fibers and aggregates of mitochondria containing paracrystalline inclusions. Molecular analysis demonstrated a GCG expansion in the poly(A)-binding protein 2 (PABP2) gene and failed to demonstrate multiple deletions of mtDNA. We hypothesize that mitochondrial abnormalities may be a secondary phenomenon. This observation may suggest that the PABP2 gene could interfere in the posttranscriptional regulation of genes involved in mitochondrial function.

Adult↗
PubMed2004

Cell response to oxidative stress induced apoptosis in patients with Leber's hereditary optic neuropathy.

OBJECTIVES: Leber's hereditary optic neuropathy (LHON) is a maternally inherited disease in which acute or subacute bilateral visual loss occurs preferentially in young men. Over 95% of LHON cases are associated with one of three mitochondrial DNA (mtDNA) point mutations, but only 50% of men and 10% of women who harbour a pathogenetic mtDNA mutation develop optic neuropathy. This incomplete penetrance and preference for men suggests that additional genetic (nuclear or mitochondrial) and/or environmental factors must modulate phenotype expression in LHON. A role for reactive oxygen species (ROS) in mitochondrial diseases, secondary to mtDNA mutations, or as a result of the direct effect of ROS cytotoxicity, has been implicated in many mitochondrial disorders, including LHON. The purpose of this study was to investigate the role of oxidative stress induced apoptosis in LHON. METHODS: The 2-deoxy-D-ribose induced apoptotic response of peripheral blood lymphocytes from six patients with LHON and six healthy subjects was investigated using light microscopy, flow cytometry, agarose gel electrophoresis, and the measurement of mitochondrial membrane potential. RESULTS: Cells of patients with LHON had a higher rate of apoptosis than those of controls and there was evidence of mitochondrial involvement in the activation of the apoptotic cascade. CONCLUSIONS: These differences in oxidative stress induced apoptosis are in line with the hypothesis that redox homeostasis could play a role in the expression of genetic mutations in different individuals and could represent a potential target in the development of new therapeutic strategies.

Antimetabolites↗
PubMed2003

Evidence of apoptosis via TUNEL staining in muscle biopsy from patients with mitochondrial encephaloneuromyopathies.

Apoptosis is an evolution-conserved form of cell death essential for development and maintenance of tissue homeostasis. Dysregulation of apoptosis has been implicated in several pathological conditions, including neurodegenerative disorders. The crucial role of mitochondria in regulation of the apoptotic pathway prompted us to investigate the pattern of apoptosis in muscle biopsies from 17 patients with mitochondrial encephaloneuromyopathies caused by mtDNA defects. The results were compared with muscle biopsies from controls and from patients with myopathies without mitochondrial impairment. The terminal deoxynucleotidyl transferase-mediated dUTP nick and labelling (TUNEL) reaction was used as marker of apoptosis. Our findings were very heterogeneous, even between patients with the same mtDNA mutations, suggesting that tissue evaluation of apoptotic process is less useful than in vitro techniques, for investigating the role of apoptosis in mitochondrial pathologies.

Adult↗
PubMed2001

Genetic leukoencephalopathies with unknown metabolic pathogenesis.

The authors describe the principal forms of genetic leucodystrophies with unknown metabolic pathogenesis, indicating their main clinical signs and the new findings concerning the molecular genetic that are useful for the laboratory confirmation of the clinical suspicion.

Demyelinating Diseases↗
PubMed1999

Studies on mitochondrial pathogenesis of Rett syndrome: ultrastructural data from skin and muscle biopsies and mutational analysis at mtDNA nucleotides 10463 and 2835.

In order to verify the pathogenic role of mitochondria in Rett syndrome, the results are reported of skin and muscle biopsies in two RS patients, showing morphological ultrastructural abnormalities in mitochondrial number and size. The investigation on two recently described mtDNA mutations (at nt 10463 and 2835) (Lewis et al., 1995; Tang et al., 1997) gave contrasting results with respect to previously reported data. In particular, the first mutation has been found in seven subjects, five of whom were from two different control groups, while the second mutation has been not detected in any of the 26 patients and controls. Although these results present some signs of a morphological impairment of mitochondria, they do not support the hypothesis that the two mutations may have a primary role in the pathogenesis of the syndrome and indicate the need for further investigations on the role of mtDNA in the pathogenesis of the syndrome.

Adolescent↗
PubMed1998

Association in the same patient of autosomal dominant progressive external ophthalmoplegia with multiple mtDNA deletions and X-linked ichthyosis: clinical, biochemical, histological, submicroscopic and molecular genetic study.

Autosomal dominant chronic progressive external ophthalmoplegia (AdPEO) is a muscle mitochondrial disorder due to multiple large scale rearrangements of the mitochondrial DNA. This disorder is probably due to a nuclear defect which causes genetic instability or an impairment in the replication of mitochondrial DNA. X-linked ichthyosis (XLI) is a skin disorder caused by a deletion in the steroid-sulphatase gene. Here we report the clinical, biochemical, morphologic and molecular genetic findings in a patient affected by both AdPEO, inherited by the father, and steroid-sulphatase-deficiency, inherited by the mother. The association in the same patient of the two inherited diseases is merely casual and does not seem to influence the phenotypic expression of the two diseases.

Aged↗
PubMed1996

The A to G transition at nt 3243 of the mitochondrial tRNALeu(UUR) may cause an MERRF syndrome.

OBJECTIVE: To verify the phenotype to genotype correlations of mitochondrial DNA (mtDNA) related disorders in an atypical maternally inherited encephalomyopathy. METHODS: Neuroradiological, morphological, biochemical, and molecular genetic analyses were performed on the affected members of a pedigree harbouring the heteroplasmic A to G transition at nucleotide 3243 of the mitochondrial tRNALeu(UUR), which is usually associated with the syndrome of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). RESULTS: The proband was affected by a fullblown syndrome of myoclonic epilepsy with ragged red fibres (MERRF), severe brain atrophy, and basal ganglia calcifications, without the MRI T2 hyperintense focal lesions which are pathognomonic of MELAS. Oligosymptomatic relatives were variably affected by lipomas, goitre, brain atrophy, and basal ganglia calcifications. Muscle biopsies in the proband and his mother showed a MELAS-like pattern with cytochrome c oxidase hyperreactive ragged red fibres and strongly succinate dehydrogenase reactive vessels. Quantification of the A3243G mutation disclosed 78% and 70% of mutated mtDNA in the muscle of the severely affected proband and of his oligosymptomatic mother respectively. Nucleotide sequencing of the mitochondrial tRNALeu(UUR) and tRNALys in the proband's muscle failed to show any additional nucleotide change which could account for the clinical oddity of this pedigree by modulating the expression of the primary pathogenic mutation. CONCLUSION: So far, MERRF has been associated with mutations of the mitochondrial tRNALys, and MELAS with mutations of the mitochondrial tRNALeu(UUR). Now MERRF may also be considered among the clinical syndromes associated with the A to G transition at nt 3243 of the tRNALeu(UUR).

Adolescent↗
PubMed1995

Thiol groups in proteins as endogenous reductants to determine glutathione-protein mixed disulphides in biological systems.

A novel method for glutathione-protein mixed disulphide (GSSP) determination, based on the use of protein sulphydryl groups as endogenous reductant and on the spectrophotometric determination of reduced glutathione, is described. The procedure is based on the observation that acid-precipitated proteins from different rat tissues rapidly release GSH from GSSP when brought to neutral pH. The basal GSSP content determined in rat liver, heart, lung, testis, spleen and brain corresponded to that reported in the literature and determined by more complex sample preparation or labor-intensive analytical procedures.

Animals↗
PubMed1995

Glutathione, glutathione utilizing enzymes and thioltransferase in platelets of insulin-dependent diabetic patients: relation with platelet aggregation and with microangiopatic complications.

Reduced glutathione (GSH) and activity of GSH related enzymes play a key role in defence against oxygen free radicals, whose production is, as known, raised in patients affected by diabetes mellitus, and at the same time they may contribute to the process of platelet aggregation. The purpose of this study was to evaluate GSH levels and activity of glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-Red), glutathione transferase (GSH-Tr), glucose-6-phosphate-dehydrogenase (G6PDH), and thioltransferase (TT) in platelets of insulin-dependent diabetic patients in fair metabolic control (mean glycated haemoglobin: 6.5%), as related to presence of retinopathy, neuropathy or nephropathy and to platelet aggregation by arachidonic acid (AA) in vitro. Mean effective dose (ED50) of AA was on average significantly lower in the group of insulin-dependent diabetic patients (0.41 +/- 0.02 mM (SEM), n = 46) as compared with that of control subjects strictly matched for age, sex and weight (0.77 +/- 0.02, n = 51; P = 0.0001). Mean platelet GSH as well as the activity of GSH related enzymes expressed as geometric mean (95% confidence intervals) were similar in diabetic patients and in controls, except for GSSG-Red whose activity was significantly higher in diabetic subjects (28.5 (14.4-57.5) mU 10(-9) platelets vs. 20.3 (8.7-56) mU 10(-9) platelets; P = 0.01). In the diabetic group TT was reduced when compared with healthy controls (3.8 (0.9-12.2) mU 10(-9) platelets vs. 6 (1.6-26.1) mU 10(-9) platelets; P = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Studies on the biological effects of ozone: 4. Cytokine production and glutathione levels in human erythrocytes.

We have investigated the effect of various concentrations of ozone on human blood aiming to correlate the production of cytokines with depletion of reduced glutathione and hemolysis. As erythrocytes constitute the bulk of blood cells and represent the main target of ozone they have been taken as a useful marker of its oxidative activity. It appears that a transient exposure (30 sec) of blood of up to 78 micrograms ozone per ml of blood does not depress the production of cytokines even though there is a slight increase of hemolysis and a small decrease of intracellular reduced glutathione. In contrast either a constant (up to 30 sec) exposure to an ozone flux or a high ozone concentration (108 micrograms/ml) markedly decreases reduced glutathione levels and depresses cytokine production.

Adult↗