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Biomedical subjects

M G Fiori

Publications and source records attributed to M G Fiori.

At least 19 recordsLinked to original sources
PubMed1995

An Italian kindred with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).

Vascular dementia is usually sporadic and associated with definite risk factors. Several cases also occur in a familial fashion, and may affect middle-aged or even younger subjects. Recently, an autosomal dominant inheritance was demonstrated in two unrelated French families, the members of which were affected by stroke-like episodes culminating in progressive dementia. Genetic linkage analysis assigned the disease locus to chromosome 19q12. We report an additional kindred of Italian origin in which at least 16 subjects presented leukoencephalopathic alterations. Recurrent strokes, psychiatric disturbances, dementia, and in 2 members, tetraplegia and pseudobulbar palsy were the hallmarks of this syndrome. Notably, 5 asymptomatic individuals had neuroradiological signs of leukoencephalopathy. Pathological examination of 1 subject revealed a widespread vasculopathy of the perforating arterioles, characterized by deposition of eosinophilic-congophilic material that did not immunostain with antibodies against prion protein, beta-amyloid, cystatin C, transthyretin, or heat-shock protein 70 and was similar to that described in the French families. Based on the maximum lod score, the most likely location for the disease locus was also mapped to chromosome 19q12, and found to coincide with the CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) locus. The present results confirm the existence of a nosologically distinct, autosomal dominant cerebrovascular disease, presenting with recurrent subcortical ischemic strokes independent of vascular risk factors.

Adult↗
PubMed1994

Defective activity of Na+,K(+)-ATPase in peripheral nerve of diabetic rats is independent of the axonal transport of the enzyme.

This study addressed the question as to whether the reduced activity of Na+,K(+)-ATPase reported to occur in diabetic nerves and to play a crucial role in the pathogenesis of diabetic neuropathy could be due to derangements in the axonal transport of the enzyme. A micromethod was developed to evaluate the ATPase accumulation in individual segments of ligated sciatic nerves from streptozotocin-induced diabetic rats. The results confirmed a approximately 40% decrease in the background activity, but showed that the enzyme was transported at similar rates in both anterograde and retrograde directions, suggesting that the decrease in its activity does not depend on an altered delivery along the axons.

Analysis of Variance↗
PubMed1994

Spontaneous isolated lipoma of the choroid plexus in the baboon.

A case of symptomless, solitary lipoma of the choroid plexus is described. The tumour was found in the left lateral ventricle of an adult female baboon (Papio papio) in the course of post-mortem examination. Routine histological investigation showed that the tumour was composed exclusively of characteristic adipose cells with scarce collagen septa and without other hamartoma-like constituents, such as glial cells, neurons, cartilage or muscle fibres. The tumour mass was lined by a typical single layer of cuboidal cells; no calcifications were observed either inside the tumour or in the adjacent periventricular regions. This case is reported in view of the rarity of such tumours of the choroid plexus in man and animals, and to throw light on their possible origin.

Animals↗
PubMed1994

Urinary bladder dysfunction in the BB/W diabetic rat: effect of ganglioside treatment on functional and structural alterations.

Urinary bladder dysfunction in the diabetic BB/W rat is characterized by infrequent irregular contractions of high amplitude. Initially these occur in the absence of detectable neuroanatomical lesions of sensory afferent and parasympathetic fibers of the pelvic nerve, which constitute the micturition reflex arc. Structural lesions consisting of progressive axonal atrophy of myelinated and unmyelinated fibers become detectable only after 4 months of diabetes. In the current study we evaluated the effect of ganglioside treatment (10 mg./kg. body weight) for one month. This drug regimen was initiated at 4 months of diabetes, when functional bladder abnormalities were well established, whereas structural lesions were yet to appear. Animals examined 1 or 3 months after termination of the one-month treatment protocol showed sustained normalization of the characteristic functional abnormalities, accompanied by prevention of the neuroanatomical lesions of sensory afferent and parasympathetic efferent myelinated fibers in the pelvic nerve. These data suggest that ganglioside treatment may be beneficial in delaying the progression of diabetic autonomic neuropathy in this experimental animal model.

Animals↗
PubMed1994

Amyloid deposits inside myocardial fibers in transthyretin-Met30 familial amyloidotic polyneuropathy. A histological and biochemical study.

A case of severe cardiac involvement is reported in a patient affected with familial amyloidotic polyneuropathy due to the Portuguese type I variant (Val-->Met30) of the transthyretin (prealbumin) molecule. Echocardiographic and hemodynamic studies suggested the presence of a progressive infiltrative cardiomyopathy that was later confirmed by endomyocardial biopsy. Amyloid deposits were found in both intra- and extra-myofiber location and thought to be related to primary involvement of the heart. Norepinephrine content of myocardial bioptic specimens was about threefold lower than normal, indicating that autonomic denervation may contribute to the maintenance and progression of cardiomyopathy. A sample obtained from the sural nerve showed a loss of myelinated fibers along with accumulation of amyloid masses in the endoneurial space. This histopathologic pattern correlated with a sharp decrease in the activity of the enzyme subserving electrochemical conduction through the axonal membrane, Na+, K(+)-ATPase.

Amyloid↗
PubMed1993

Decrease of nerve Na+,K(+)-ATPase activity in the pathogenesis of human diabetic neuropathy.

A decrease in Na+,K(+)-ATPase activity is claimed to play a central role in the pathogenesis of electrophysiological and morphological abnormalities that characterize the neuropathic complications in different animal models of diabetes mellitus. The peripheral nerves from 17 patients with either type I or type II diabetes mellitus were studied to assess the importance of changes in Na+,K(+)-ATPase activity in chronic human diabetic neuropathy. Sixteen nerves from age- and sex-matched normal individuals, and 12 nerves from non-diabetic neuropathic subjects undergoing vascular or orthopedic surgery served as negative and positive controls, respectively. All specimens were processed blind. Ouabain-sensitive ATPase activity was measured by a modified spectrophotometric coupled-enzyme assay. Standard histology, fiber teasing and electron microscopy were used to establish the normal or neuropathological patterns of surgical material. Morphometric analysis permitted calculation of fiber density in each nerve specimen and correlation of this figure with the relevant enzymatic activity. Na+,K(+)-ATPase activity was approximately 59% lower in nerves from diabetic patients than in normal controls (P < 0.01) and approximately 38% lower in nerves from non-diabetic patients with neuropathy (P < 0.01). Although nerves from both neuropathic conditions had significantly fewer fibers than those from normal individuals (diabetic -33%, and non-diabetic -22%), the decreases in Na+,K(+)-ATPase activity and fiber density were not correlated only in specimens from diabetic patients (r2 = 0.096; P = 0.22). Taken together with data from experimental animal models, these results suggest that the reduction in Na+,K(+)-ATPase activity in diabetic nerves is not an epiphenomenon secondary to fiber loss; rather, it may be an important factor in the pathogenesis and self-maintenance of human diabetic neuropathy.

Adult↗
PubMed1993

Effect of gangliosides on diacylglycerol content and molecular species in nerve from diabetic rats.

The effects of ganglioside treatment on 1,2-diacylglycerol content and on molecular species in 1,2-diacylglycerol, phosphatidic acid and total diacylglycerolipids, as well as Na+,K(+)-ATPase activity, were examined in sciatic nerves from streptozotocin-induced diabetic rats. Beginning 2 weeks after induction of diabetes, animals were administered mixed bovine brain gangliosides, AGF1, an inner ester derivative of this mixture, or saline for 5 weeks. The levels of 1,2-diacylglycerol and arachidonoyl-containing molecular species in age-matched non-diabetic animals were not affected by ganglioside treatment. In nerves from saline-treated diabetic animals, 1,2-diacylglycerol levels were not reduced, but both Na+,K(+)-ATPase activity and all arachidonyl-containing species except for 18:0/20:4 1,2-diacylglycerol were significantly decreased. The content of 1,2-diacylglycerol was lowered by 23 and 16% in bovine brain ganglioside and AGF1-treated diabetic animals, respectively, and the quantity of 18:0/20:4 1,2-diacylglycerol was also selectively reduced. Ganglioside administration did not affect the diminished levels of arachidonoyl-containing molecular species in 1,2-diacylglycerol, phosphatidic acid or diacylglycerolipids in nerve from diabetic rats. In the same nerves, bovine brain gangliosides partially and AGF1 completely restored Na+,K(+)-ATPase activity. The results suggest that gangliosides depress the content of total 1,2-diacylglycerol and the quantity of 18:0/20:4 1,2-diacylglycerol, specifically, in diabetic nerve. The possible relationship between the corrective action of gangliosides on Na+,K(+)-ATPase activity and the effect of these substances on 1,2-diacylglycerol molecular species composition and metabolism is discussed.

Animals↗
PubMed1993

Cognitive decline in the elderly: a double-blind, placebo-controlled multicenter study on efficacy of phosphatidylserine administration.

This double-blind study assesses the therapeutic efficacy and the safety of oral treatment with phosphatidylserine (BC-PS) vs placebo (300 mg/day for 6 months) in a group of geriatric patients with cognitive impairment. A total of 494 elderly patients (age between 65 and 93 years), with moderate to severe cognitive decline, according to the Mini Mental State Examination and Global Deterioration Scale, were recruited in 23 Geriatric or General Medicine Units in Northeastern Italy. Sixty-nine patients dropped out within the 6-month trial period. Patients were examined just before starting therapy, and 3 and 6 months thereafter. The efficacy of treatment compared to placebo was measured on the basis of changes occurring in behavior and cognitive performance using the Plutchik Geriatric Rating Scale and the Buschke Selective Reminding Test. Statistically significant improvements in the phosphatidylserine-treated group compared to placebo were observed both in terms of behavioral and cognitive parameters. In addition, clinical evaluation and laboratory tests demonstrated that BC-PS was well tolerated. These results are clinically important since the patients were representative of the geriatric population commonly met in clinical practice.

Activities of Daily Living↗
PubMed1993

An electrophysiological study of visual processing in Alzheimer's disease.

Visual processing of sinusoidally modulated gratings was studied in a group of patients (n = 11) with Alzheimer's disease (AD) and an elderly normal control group (n = 9). Spatial square wave gratings (1.47 c/d) were reversed at a temporal frequency of 4 or 8 Hz. EEG recordings at rest and during visual stimulation were obtained from 20 channels using the 10/20 international system. The power spectrum of the 2nd and 4th harmonic of the stimulation frequency was calculated by Fast Fourier Transform (FFT) at a resolution of 0.25 Hz. Association of activity between occipital, temporal, parietal and central regions was measured by intra- and inter-hemispheric coherence and phase at harmonics of the stimulation frequency. A significant difference (P < 0.01) in evoked activity of the 4th harmonic at O1 and O2 was found between the two groups with less activity in the AD patients. In the AD group there was a significant correlation (P < 0.05) between evoked activity at the 2nd harmonic of the 8 Hz visual stimulation and Mini-Mental State (MMS) score. This correlation was independent of the age effect on MMS. Response phase between O1 and O2 for both 4 and 8 Hz stimuli was close to 0 degree C and coherence had similar values in both groups. Occipital and central regions showed a phase reversal for all harmonic responses to both visual stimuli. The AD patients showed statistically significant (P < 0.05) phase dispersion at O1-P3 and O2-P4 not seen in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Pancreatic gangliosides delay the onset of insulitis and hyperglycaemia in the low-dose streptozotocin mouse model.

Gangliosides have been shown to modulate autoimmune phenomena in experimental diabetes. The effects of a pancreatic ganglioside preparation or of a commercial brain ganglioside mixture on the insulitis and blood glucose levels in the low-dose streptozotocin mouse model of diabetes have been investigated. Fifty-five C57BL/6J male mice were grouped as follows: Group 1 (n = 20) was injected intraperitoneally with repeated low doses of streptozotocin; Group 2 (n = 10) received streptozotocin as above but was also injected with a pancreatic ganglioside preparation equivalent to 2 micrograms sialic acid 2 h before each streptozotocin dose; Group 3 (n = 15) received streptozotocin and brain-derived gangliosides in the same dose as that of pancreatic gangliosides; Group 4 (n = 10) consisted of normal animals. Half of the mice were killed on day 12 and the others on day 24 from the beginning of treatment. On day 12, among the streptozotocin-injected animals only those treated with pancreatic gangliosides remained normoglycaemic, whereas on day 24 all streptozotocin mice were hyperglycaemic. Such a result paralleled the data pertaining to insulitis scores. In conclusion, pancreatic gangliosides have a short-term protective role on the development of diabetes in the low-dose streptozotocin model, an effect therefore linked to tissue-related differences in the glycosphingolipid composition.

Animals↗
PubMed1993

Neurotoxicity of nonionic low-osmolar contrast media. A receptor binding study.

RATIONALE AND OBJECTIVES: The use of the newest nonionic, water-soluble, low-osmolar radiographic contrast media (CM) is still associated with occasional adverse reactions affecting the neural tissues. Because these CM display lipophilic potential in their interactions with biological membranes when diffusing within the brain parenchyma, they could affect neurotransmitter binding to the receptors. Two representative nonionic CM, iopamidol and iohexol, were studied to assess whether CM-related neurotoxicity derived from their interactions with specific receptors on neural membranes. METHODS: Binding assays were carried out in vitro on crude total membrane or crude synaptic membrane preparations from selected brain areas (cortex, striatum, hippocampus, cerebellum). The concentrations of CM and reference drugs that reduce specific binding of each ligand by 50% of its maximum value (IC50) were determined using radioligands to the receptors of the most common neurotransmitters in the central nervous system, including excitatory amino acids. RESULTS: Neither iopamidol nor iohexol inhibited the (3H) ligand binding to any kind of receptor up to very high concentrations (100 microM). CONCLUSIONS: The nonionic, low-osmolar CM did not influence the normal functions of neural membranes in our model. This suggests that occasional neurotoxic effects do not occur as a consequence of specific action on brain receptors. These CM may have an indirect, postmembrane site of action.

Animals↗
PubMed1992

Functional correlates of a three-component spatial model of the alpha rhythm.

We applied a three-component (temporal, occipital and parietal) spatial model to EEG data obtained from 46 young and 11 elderly subjects. With closed eyes the mean alpha frequency was 9.51 Hz for the temporal, 9.88 Hz for the occipital and 10.14 Hz for the parietal component. The power of the occipital component was larger than that of the others. With open eyes it was reduced to the same level as the temporal and parietal components. The power of the occipital component decreased significantly with age.

Adult↗
PubMed1992

Gangliosides prevent the inhibition by K-252a of NGF responses in PC12 cells.

K-252a, a general kinase inhibitor, selectively blocks the actions of nerve growth factor (NGF) in PC12 cells. Since gangliosides have been reported to modulate neuronal cell responsiveness to NGF and to regulate several protein kinases, the ability of these compounds to reverse the inhibition by K-252a was tested. Parameters at both short- and long-term times following treatment of PC12 cells with NGF were analyzed which are known to be either transcription-dependent or -independent events. Gangliosides were found to completely prevent the inhibition by K-252a of NGF-induced neurite regeneration and c-fos induction, and partially also that of protein kinase N activation. The ganglioside protective effects were concentration-dependent and required the intact molecule. These findings raise the possibility that gangliosides might affect a specific pathway of NGF responses sensitive to inhibition by K-252a.

Animals↗
PubMed1992

Choline acetyltransferase activity in murine thymus.

Murine thymus has been demonstrated to contain both cholinergic receptors and acetylcholinesterase activity. In the present study we have investigated the presence of the enzyme choline acetyltransferase in this organ, which is responsible for the synthesis of acetylcholine. Results reported here demonstrate that (1) an appreciable amount of the enzyme is already present in the thymus on the day of birth; (2) its expression is developmentally regulated; and (3) thymic atrophy, induced in young (2-week-old) and adult (6-week-old) mice by i.p. injection of hydrocortisone for 2 days, is accompanied by significant reduction of choline acetyltransferase activity only in young mice. Altogether these results demonstrate the presence in the murine thymus of functionally relevant markers of the cholinergic system that might interface the interactions between the nervous and immune systems.

Acetylcholine↗
PubMed1992

Motor unit function during evolution of proximal axonal swellings.

beta,beta'-Iminodipropionitrile (IDPN) impairs axonal transport of neurofilaments; their accumulation leads to the formation of proximal swellings in motor axons. Similar proximal swellings are a feature of some cases of motor neuron disease such as amyotrophic lateral sclerosis (ALS). Motor units in IDPN-treated animals were assessed to determine their relative susceptibilities to impaired function and whether the functional changes resulting from proximal axonal swellings share certain electromyographic features with ALS. Intrinsic properties of medial gastrocnemius motoneurones (MN) and contractile responses of their motor units were examined during the evolution of proximal axonal swellings in cats administered IDPN (50 mg/kg once weekly) for 7, 14 or 35 days. While conduction velocities were significantly decreased in all motor unit types by 35 days, the conduction slowing was greater in fast fatigable (types FF and FI) motor units than in fatigue resistant (types FR and S) motor units. Normal correlations between axonal conduction velocity and MN input resistance (Rin) and the inverse relationship between Rin and rheobase were lost with progression of the neuropathy. Twitch and maximum tetanic tension developed by fast-fatigable motor units declined early in the neuropathy, whereas fatigue-resistant units did not show similar changes until later stages of the intoxication. In some motor units, irregular and abnormal tetanic tensions were elicited by repetitive MN discharge. At 14 and 35 days, a novel, intermediate motor unit response classified as slow and fatigable (SF) was observed. Conduction block, characterized by repetitive MN firing without a corresponding contractile response, was observed in some type FF and S units by 35 days. Morphometric analysis of muscle fiber types showed significant atrophy, particularly in the type I fibers at 14-35 days; the atrophy reversed following cessation of IDPN administration. The influence of proximal axonal swellings on motor unit function in IDPN neuropathy is discussed in terms of reported electrophysiological alterations in motoneurone disease.

Action Potentials↗