Biomedical subjects

M G Fiori

Publications and source records attributed to M G Fiori.

At least 37 records · Page 2Linked to original sources

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↗

PubMed1992

Effect of parenteral administration of GM1 on cytokines and anti-ganglioside antibody patterns. Preliminary report in normal human individuals.

To assess the effects of monosialoganglioside GM1 on some immunological parameters, 12 healthy men were treated with 100 mg GM1 i.m. daily for 15 days. Before and after treatment, the following were studied: (1) serum levels of antibodies against GM1, asialo-GM1 (aGM1), GM2 and GD1b; (2) serum levels of interleukin (IL)-1 beta, IL-2, soluble IL-2 receptor (sIL-2R), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma); (3) IL-1 beta and TNF-alpha production by peripheral blood monocytes (PBMO). Anti-ganglioside antibody and cytokine serum levels were not affected by exogenous GM1 administration with the exception of a transient increase in anti-GM1 antibody titer observed in one subject. In addition, no inhibition of IL-1 beta and TNF-alpha production by PBMO was observed. These preliminary data do not support a potential immunogenic or immunomodulatory function for in vivo administered GM1.

Adolescent↗

PubMed1992

Brainstem auditory evoked potentials in rats with streptozotocin-induced diabetes.

Brainstem acoustic evoked potentials (BAEPs) were studied in streptozotocin (STZ)-diabetic rats and age-matched controls at 3 and 5 months from induction of the pathology. The diabetic status of the animals was kept uncontrolled throughout the study. Body weight and glycosylated hemoglobin were markedly altered in the diabetic animals (-42%, and +120% of control values, respectively). Neurophysiological results showed an increase in the latency of the major components of BAEPs; this increase was clearly time-dependent for the peripheral component (peak I). The central component (peak IV) was also significantly delayed. However, no significant impairment of the central conduction time was demonstrated by examining the interpeak I-IV latency. In conclusion, BAEPs prove to be a useful non-invasive neurophysiological technique that may help unravel both the relative involvement of the peripheral and central nervous systems in the course of diabetes mellitus, and the evolution of diabetic neuropathy.

Analysis of Variance↗

PubMed1992

Comparative ototoxic potential of hyaluronic acid and methylcellulose.

In experimental animal studies, exogenous hyaluronan (HA) has been shown to exert beneficial effects on the healing of tympanic membrane perforation. As any other exogenous substance, HA may prove potentially toxic, by filling the middle ear cavity, to the sensory cells of the organ of Corti. Electrophysiological (ABR) and morphological studies were carried out in the rat to examine the auditory function and the structure of the sensory epithelium. Rats received either HA or hydroxy-propyl-methyl-cellulose by trans-tympanic injection (middle ear cavity was completely filled up) and were compared to untreated, age- and weight-matched rats. In both treated groups ABR revealed transitory, mild conduction hearing loss, in particular for high frequencies, until day 7 postinjection. This loss recovered completely within the 15th day. Morphologically, no significant degenerative/necrotic lesions were observed in the organ of Corti, from both treated groups.

Animals↗

PubMed1992

Innervation of the paralyzed laryngeal muscles by phrenic motoneurons. A quantitative study by light and electron microscopy.

In the cat, inspiratory opening of the paralyzed glottis recovered after unilateral or bilateral reinnervation of the posterior cricoarytenoid (PCA) muscles by phrenic axons. The morphometric analysis of the regenerated recurrent laryngeal nerves (RLNs), showed that proliferation was abundant; 4 months after the nerve anastomosis, more than 500 myelinated axonal branches repopulated the RLNs. The mean diameter of motor axons (3.5 to 5.0 microns) was lower than in normal phrenic and RLN (8 to 10 microns), and the mean internode length was about half that of the normal RLN. Histochemical examination of the PCA muscle revealed that muscle fiber composition (44% type I and 56% type II muscle fiber) was fairly similar to that of normal PCA. The contraction time of the reinnervated muscles was as long as 60 msec at the time of movement recovery, but it shortened to 25 to 30 msec when the reinnervation time increased. These anatomical and functional results support the choice of the phrenic nerve for laryngeal reinnervation.

Adenosine Triphosphatases↗

PubMed1992

Experimental diabetic neuropathy. Effect of ganglioside treatment on axonal transport of cytoskeletal proteins.

Abnormalities in axonal transport of proteins are thought to play an important role in the pathogenesis of diabetic neuropathy. Gangliosides exert a positive action on numerous alterations in biochemistry and physiology of diabetic nerves. This study was undertaken to assess the effects of exogenous gangliosides on the axonal transport of structural proteins such as actin and tubulin in the sensory fibers of short-term (9-wk) and long-term (6-mo) diabetic rats. Adult Sprague-Dawley rats were made diabetic with a single injection of 70 mg/kg streptozocin i.p. Subgroups were injected daily with either highly purified ganglioside mixture (10 mg/kg i.p.) or saline for 1 mo, beginning either 2 or 17 wk after streptozocin injection. Age-matched rats were used as controls. Axonal transport was studied by the pulse-labeling technique. Three weeks after labeling, sciatic nerves were dissected out and processed for sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fluorography. In diabetic rats of both experimental designs, the transport rate of tubulin and actin was decreased by approximately 30% compared with control rats. Ganglioside treatment counteracted such alterations in both 9-wk and 6-mo diabetic rats. These data suggest a pharmacological effect that could be correlated with molecular interactions between integral membrane glycolipids and cytoskeletal elements.

Actins↗

PubMed1992

[Cholelithiasis. Ultrasonography and other diagnostic methods. Usefulness, indications, and limitations].

It is reported that 12.5% of the Italian population suffer from cholecystopathy. The Authors carried out a retrospective analysis of the cases observed over an 18-month period. It was found that ultrasonography was the most appropriate screening method to reveal cholecystic pathologies and diseases of the biliary tract since it is specific and sensitive and also enables adjacent organs to be examined (liver, kidneys, aorta, pancreas, spleen).

Adult↗

PubMed1991

Regional changes in spinal cord glucose metabolism in a rat model of painful neuropathy.

Spinal cord patterns of metabolic activity in a model of neuropathic pain were assessed in unanesthetized rats by the [14C]-2-deoxyglucose (2-DG) technique. Rats used in this procedure had demonstrable thermal hyperalgesia ipsilateral to sciatic nerve ligation and ipsilateral hindpaws that were lifted in a guarded position. The latter indicated possible spontaneous pain. Sciatic nerve ligation produced significant increases in glucose utilization in the dorsal and ventral horns of both sides, with greater activity present on the ipsilateral as compared to the contralateral side. Peak activity was in laminae V-VI, a region involved in nociceptive processing. Thus, a chronic increase in neuronal activity in these regions may reflect spontaneous neuropathic pain.

Animals↗

PubMed1991

Effects of gangliosides on the expression of autoimmune demyelination in the peripheral nervous system.

To test whether gangliosides (GA) might exert neuritogenic effects in vivo, experimental allergic neuritis (EAN) was studied clinically, neuropathologically, and immunologically in Lewis rats immunized with bovine peripheral nerve, P2 myelin protein, P2 myelin protein plus two different doses of GA, P2 with galactocerebroside (GC), and GA alone, each emulsified in adjuvant. All except the GA-treated group developed signs of EAN between days 11 and 14 after the injection. Rats immunized with P2 alone were the most severely affected. Rats given P2 plus GA and those given P2 plus GC displayed a significantly lower clinical score. Histological analysis revealed a comparable degree of inflammation of the peripheral nervous system and demyelination in the spinal nerve roots of bovine peripheral nerve- and P2-immunized rats. The P2 plus GA and P2 plus GC groups revealed similar degrees of pathology in the spinal nerve roots but the latter group stood apart from the rest in that it showed widespread peripheral nervous system changes extending distally into the sciatic nerve. Serological analysis demonstrated that P2 and GC, but not GA, elicited antibody (IgG) responses, but there was no correlation between antibody titer and clinical or histological involvement. The present data fail to support an enhancing role for gangliosides in the expression of EAN and, by extrapolation, in the Guillain-Barré syndrome, for which EAN serves as the laboratory model, and in which suggestions have been made that antibodies to GA may have pathogenetic significance.

Animals↗

PubMed1991

Perineurium of sciatic nerve in normal and diabetic rodents: freeze-fracture study of intercellular junctional complexes.

A comparative study has been carried out using the freeze-fracture technique on the perineurium of the sciatic nerve from normal and diabetic mice (C57Bl/Ks, BALB/c and CD1 strains) and rats of various ages. The replicas showed that tight junctions connected perineurial cells both within the same cell layer (zonulae occludentes) and between adjacent layers (maculae occludentes). In neonates, a number of zonulae occludentes were characterized by short, incomplete or fragmented ridges at various intervals from each other; in adults, tight junctions appeared as 'mature' networks of interconnected, branching and/or anastomosing strands. Zonulae occludentes of diabetic mice also exhibited frequent interruption of the strands and reduction in the branching of strands. Gap junctions occurred in both zonulae and maculae occludentes of normal and diabetic rats at all ages. In the C57Bl/Ks strain such junctions occurred more frequently in zonulae occludentes of diabetic animals. It is suggested that perineurial cells are coupled by gap junctions to allow fast transfer of ions and small-sized molecules across the layers; under pathological conditions, such as diabetes, the increase in cell-to-cell signalling may be important in controlling the abnormal metabolic situation.

Aging↗

PubMed1991

Rat NGF receptor is recognized by the tumor-associated antigen monoclonal antibody 217c.

The expression of the epitope recognized by the tumor-associated antigen monoclonal antibody 217c increased on cultured rat Schwann cells with time. The same phenomenon has previously been reported for the rat nerve growth factor (NGF) receptor by using monoclonal antibody 192-IgG. The distribution of 217c antibody immunoreactivity closely paralleled that observed for NGF receptors on NGF-primed pheochromocytoma (PC12) cells in culture and a number of central neurons in vivo. Immunoprecipitation of affinity-labeled NGF receptors was used to examine whether these two antibodies shared common or unique antigens. Both the quantitative data and the electrophoretic mobility of the immunoprecipitated 125I-NGF/receptor complex indicate that the antigen recognized by the 217c mAb monoclonal antibody is, in fact, the NGF receptor. Furthermore, binding studies indicated that 192-IgG and 217c recognize different epitopes on the same molecule. The characterization of the 217c antibody should provide a valuable new tool in the study of NGF receptors.

Adrenal Gland Neoplasms↗

PubMed1991

Inner ester derivatives of gangliosides protect autonomic nerves of alloxan-diabetic rats against Na+, K(+)-ATPase activity defects.

Bovine brain gangliosides have been shown to prevent decay in Na+,K(+)-ATPase activity in sciatic and optic nerves of alloxan- and streptozotocin-diabetic rats. In the search for a drug with greater bioavailability and increased incorporation into neural tissue, ganglioside inner ester derivatives (AGF1) were recently developed. We evaluated the effect of AGF1 treatment on Na+,K(+)-ATPase activity in homogenates of vagus nerve from alloxan-diabetic rats (100 mg/kg s.c.). Animals were treated with AGF1: 10 mg/kg 6 days/week i.p., or 30 mg/kg biweekly i.p. Treatment began 10 d post-alloxan and continued for 8 consecutive weeks. Normal age- and sex-matched rats were used as controls. Alloxan intoxication produced a 39% decrease in Na+,K(+)-ATPase activity of the vagus nerve, which was completely restored (96-97% recovery) by both AGF1 regimes. Results suggest that ganglioside inner ester derivatives may be used in the clinical setting for the management of diabetic autonomic neuropathy.

Animals↗

PubMed1990

[Spontaneous hematoma of the abdominal wall].

Spontaneous hematoma of the abdominal wall is an unusual event which has an aspecific symptomatology, common to other diseases. There are factors which create a predisposition to the formation of hematoma and others which trigger off this phenomenon. The paper reports 8 patients, aged between 35 and 85 years: predisposition, symptomatology, characteristics of hematoma and therapy are illustrated in a table. Diagnosis was generally made using ultrasonography and the prognosis was always benign.

Abdominal Muscles↗

PubMed1990

Diabetic neuropathy in db/db mice develops independently of changes in ATPase and aldose reductase. A biochemical and immunohistochemical study.

ATPase activity was investigated in sciatic and optic nerves of female mutant diabetic C57Bl/Ks (db/db) mice and age-matched control mice (db/m and m/m). Nerves from animals aged 50, 70, 125, 180 and 280 days were assayed in vitro for ATPase activity in the presence or absence of ouabain: the ouabain-sensitive fraction contained Na+,K(+)-ATPase. Enzymatic activity was compared within and between age-matched groups. No significant difference in Na+,K(+)-ATPase activity was detected between the diabetic and control mice, whether expressed as mumol Pi/h-1 formed per gramme wet weight or per nerve (protein content). The activity decreased by about 25% in both the sciatic and optic nerves of the oldest animals. These results were strikingly similar in all groups, regardless of the type of nerve examined, confirming that the development of neuropathy in this animal model is unrelated to the postulated derangement of Na+,K(+)-ATPase activity. Among possible explanations, a lack of polyol pathway activation was investigated by staining the sciatic nerves of animals from all groups with the peroxidase-antiperoxidase procedure using a polyclonal antiserum raised against the enzyme aldose reductase. Histological sections of all nerves were consistently negative, suggesting that these animals actually lack the enzyme involved in activating the self-perpetuating metabolic cycle leading to deranged nerve function. The db/db mouse appears to present particular biochemical changes which merit attention with a view to clarifying the pathogenesis of diabetic neuropathy.

Adenosine Triphosphatases↗