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Biomedical subjects

M G Fiori

Publications and source records attributed to M G Fiori.

At least 55 records · Page 3Linked to original sources

Intravenous urography with iopamidol in children with reflux and obstructive nephropathy: effects on glomerular and tubular functions and the renin-angiotensin-aldosterone system.

Twenty-seven children [2 with chronic renal failure (CRF)] with reflux or obstructive nephropathy underwent intravenous urography with iopamidol 370, a nonionic contrast medium 1 (CM), osmolality 796 mosmol/kg, for renal growth evaluation. Mean iopamidol dosing was 1.69 ml/kg (range 1.22-2.42); the 2 children with CRF received 2 and 2.42 ml/kg respectively. One hour after infusion a significant decrease in haematocrit, haemoglobin, plasma sodium (Na+), chloride (Cl-), renin activity and aldosterone was observed, consistent with a possible plasma volume expansion due to the slightly hypertonic CM. At the same time there was a significant increase in fractional excretion of Na+, Cl- and potassium, probably due to the haemodynamic effects and tubular response to a substance acting as on osmotic diuretic. The -24 to +48 h monitoring of albuminuria, beta-2-microglobulin excretion, and in 4 children excretion of N-acetyl-beta-glucosaminidase and alanine-aminopeptidase did not show any relevant nephrotoxicity. No untoward effect of clinical relevance was observed.

Adolescent↗

Efficacy of ganglioside treatment in reducing functional alterations induced by vincristine in rabbit peripheral nerves.

Vincristine (VCR) administration to rabbits resulted in severe electrophysiologic alterations of peripheral nerves. Sciatic nerve conduction velocity, compound action potential (CAP) amplitude, and area under the CAP waveform were all reduced in a dose-dependent fashion. In addition, the pattern of conduction velocity of both motor and sensory fibers was altered and shifted toward slow conduction classes. Simultaneous treatment with gangliosides limited significantly the changes in electrophysiologic parameters induced by VCR. It is suggested that gangliosides be given in the clinical setting as protection for the peripheral nerves against the side effects of antiblastic therapy.

Action Potentials↗

Cystometric changes in alloxan diabetic rats: evidence for functional and structural correlates of diabetic autonomic neuropathy.

Autonomic neuropathy and urinary bladder function were compared in Sprague-Dawley rats with alloxan-diabetes of 3 months duration, rats fed sucrose for 8 weeks, and rats examined 8 weeks after pelvic nerve surgical axotomy; normal age-matched rats were used as controls. All experimental interventions induced bladder hypertrophy with increased bladder weight. In diabetic and sucrose-fed animals, water intake and urinary output increased. Cystometric recordings of normal rats in vivo showed rhythmic contractions (1.25 +/- 0.25 contr/min) with threshold volume for micturition reflex at 0.51 +/- 0.04 ml. In diabetic rats, bladder contractions were irregular and of lower frequency (0.60 +/- 0.04 contr/min), while threshold volume was significantly higher (1.00 +/- 0.11 ml). Bladder contractions were normal in sucrose-fed animals, though threshold volume was markedly augmented (1.27 +/- 0.19 ml). Pelvic nerve surgical ablation abolished micturition reflex. In bladder strips excised post-mortem, contractile response to field stimulation was reduced in diabetic rats compared to control and sucrose-fed animals. Morphological examination of pelvic and hypogastric nerves revealed abnormalities characteristic of diabetic neuropathy only in diabetic rats. These data suggest that in alloxan-induced diabetes the decrease in the rate of bladder contraction is the result of autonomic neuropathy; while bladder hypertrophy in sucrose-fed rats appears to be an organ adaptation to hyperdiuresis.

Alloxan↗

Protective effects of a monosialoganglioside derivative following transitory forebrain ischemia in rats.

We evaluated the effects of treatment with the inner ester derivative of the monosialoganglioside GM1 on cortical electroencephalographic activity and hippocampal CA1 morphology after transitory, near-complete cerebral ischemia in rats. Ischemia was induced by the four-vessel occlusion method, and we studied only the 58 rats that showed flattening of the cortical electroencephalogram for the entire 30 minutes of occlusion. The ganglioside (n = 30) or saline (n = 28) was administered intravenously immediately after release of the carotid clips and then intramuscularly for 21 days of observation. Cortical electroencephalographic activity was monitored throughout the experiment. After 21 days of recirculation we assessed hippocampal CA1 damage by light microscopy. The results indicate that treatment with the ganglioside reduces postischemic secondary damage to the cortical circuitry (as indicated by significantly higher cortical electroencephalographic activity late after reperfusion) and limits neuronal loss in the CA1 region. Our results lend support to the possible therapeutic use of ganglioside in human pathologic conditions associated with cerebrovascular insufficiencies.

Animals↗

Correction of altered metabolic activities in sciatic nerves of streptozocin-induced diabetic rats. Effect of ganglioside treatment.

The effect of ganglioside administration to nondiabetic and streptozocin-induced diabetic rats on sciatic nerve Na(+)-K(+)-ATPase, polyphosphoinositide (PPI) turnover, and protein phosphorylation was investigated. Gangliosides were injected (10 mg/kg body wt i.p.) for 10 or 30 days beginning 20 days after induction of diabetes. Na(+)-K(+)-ATPase activity was reduced nearly 50% in diabetic nerve and was restored to normal by both ganglioside treatments. The elevated levels of fructose and sorbitol and depressed content of myoinositol in diabetic nerve were unaffected by 30 days of ganglioside treatment, indicating that the restoration of Na(+)-K(+)-ATPase activity is not dependent on normal concentrations of these compounds. In the same nerves, 32P incorporation into phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 4-phosphate increased 73-76 and 39-53%, respectively, in diabetic compared with nondiabetic tissue. Ganglioside administration abolished the elevated labeling of PPIs after 30 days but was ineffective after only 10 days. Neither ganglioside regimen was able to reverse enhanced phosphorylation of the major peripheral nerve myelin protein P0. The finding that gangliosides can more quickly correct the effects of diabetes on Na(+)-K(+)-ATPase activity than on PPI turnover suggests that the mechanisms underlying these two phenomena are not closely related and are distinct from the sequence of events responsible for altered myelin protein phosphorylation.

Animals↗

Functional evaluation of acute vincristine toxicity in rat skeletal muscle.

Vincristine sulfate (VCR) was administered intravenously to rats at doses of 0.25, 0.5, and 0.75 mg/kg. During the first week following VCR treatment, extensor digitorum longus (EDL) muscle contraction strength and fiber electrophysiologic parameters were measured. At all doses tested, VCR strongly reduced twitch and tetanic tension. EDL fiber resting membrane potential was affected in a dose-dependent manner, and membrane depolarization was associated with the loss of excitability. Local membrane hyperpolarization by intracellular current application restored the capacity to produce action potential (AP). However, to elicit APs with a normal rate of rise, polarizing current had to be maintained for 3-5 minutes, indicating that the removal of Na+ channel inactivation followed a slow kinetics. Minor alterations in spontaneous synaptic transmission and in evoked transmission during high-frequency repetitive stimulation were seen only at the highest dose. It is suggested that VCR impairs skeletal muscle function by affecting primarily the contractile apparatus, whereas sarcolemmal alterations are evident at increased doses of the drug.

Action Potentials↗

Spontaneous and nerve-evoked quantal transmission in regenerated motor terminals.

Quantal acetylcholine release was studied in sciatic nerve-extensor digitorum longus muscle preparations from normal rats and in reinnervated muscles at different times following peroneus nerve crush. The efficiency of nerve-evoked transmission was regained almost completely at a time (20 days after crush) when the secretory response to increased extracellular K+ was very weak. This suggests that K+-induced secretion might be activated through mechanisms at least partially different from those involved in the response to nerve stimulation.

Animals↗

Ganglioside treatment and improved axonal regeneration capacity in experimental diabetic neuropathy.

The efficacy of gangliosides in enhancing axonal regeneration and maturation in the early stages of diabetic neuropathy was assessed by quantitative analysis of immunostained serial sections of the sciatic nerve. Sprague-Dawley rats were made diabetic with a single injection of alloxan (100 mg/kg). One week later they were injected daily intraperitoneally with either a highly purified ganglioside mixture (10 mg/kg) or sterile saline for 4 wk. At the end of the treatment, sciatic nerves were crushed and allowed to regenerate for 1 wk without ganglioside treatment. The animals were then killed, and the nerves were frozen and processed for immunohistochemistry and electron microscopy. The number of regrowing axons was counted with a computerized image-analysis system on cross sections taken at predefined distances along the regenerating stump and stained with monoclonal antibody iC8 specific for the 145,000-Mr subunit of the neurofilaments. In untreated diabetic animals the number of axons able to regenerate and sustain elongation for greater than or equal to 13 mm from the crush point was reduced by 40% with respect to control rats. Ganglioside treatment was effective in compensating almost completely for this dramatic reduction. Electron microscopy confirmed that the immunofluorescence counts corresponded to regenerating axons containing neurofilaments. These results suggest that gangliosides are able to compensate for the derangements of axonal transport of cytoskeletal proteins reported in experimental diabetic neuropathy.

Alloxan↗

Histochemical study of Sarcocystis sp. intramuscular cysts in gastrocnemius and soleus of the cat.

Histochemical investigations of Sarcocystis microcysts found in two hindleg muscles of cats were carried out. Genus identification was based on the reinforced cyst membrane structure and its dimensions, the structure of the sarcocysts, and an electron microscopic survey of bradyzoite characteristics. The cyst membrane is partly contributed by the host myofiber, the characteristic histochemical features of which it retains. Materials adjacent to the limiting membrane make it appear thicker than it actually is, particularly when the PAS method as well as techniques for the demonstration of alpha-glycerophosphate dehydrogenase and ATPase activities are used. The ground substance occupying the parasitophorous vacuole is not amorphous and metabolically inert, but rather displays a fairly strong and definite ATPase activity, suggesting a trophic role in the support of metrocytes and zoites embedded therein. Cysts tend to adapt their biochemical characteristics to the particular metabolism of the muscle fibers in which they are located. All of these findings are discussed in terms of host-parasite relationships.

Animals↗

Adaptation of sarcolemmal action potential mechanisms to chronic depolarization in denervated skeletal muscle.

Action potential properties were studied in rat extensor digitorum longus fibers, at different times after locally setting the membrane to a holding potential of -90 mV. Whereas in normal muscles holding potential duration had little effect on the action potential, the holding potential duration markedly influenced membrane excitability in the fibers previously depolarized by increasing the K+ concentration of the bathing medium. In this case, when the holding potential was prolonged from 20 to 180 s, action potential overshoot, maximum rate of rise, and maximum rate of fall increased 1.8-, 3.1-, and 1.8-fold, respectively. In the denervated muscle, overshoot and maximum rate of fall were dependent on the duration of holding potential application until denervation day 6, whereas maximum rate of rise was affected throughout the duration of this study (15 days of denervation). However, 180-s application of -90 mV holding potential elicited about a 2-fold increase of maximum rate of rise in the earlier denervation stages, and only a 1.5-fold increase at later times. These observations suggest that ultra-slow processes of Na+ conductance inactivation were less effective after 6 days of denervation. Correspondingly, extensor digitorum longus fibers acquired the ability to generate action potentials at a depolarized holding potential. The partial removal of ultra-slow Na+ inactivation after muscle denervation could substantially contribute to a general process of membrane adaptation, resulting in the capacity of voltage-dependent ion channels to operate in a condition of chronic depolarization.

Action Potentials↗

Ganglioside treatment of vincristine-induced neuropathy. An electrophysiologic study.

A 5-week treatment with vincristine (0.20 or 0.25 mg/kg, i.v., once/week) in the rabbit produced a peripheral neuropathy characterized by both morphologic and electrophysiologic alterations. In particular, electrophysiologic recordings demonstrated that the amplitude, area and conduction velocity of compound action potential (CAP) were consistently reduced in a dose-dependent manner. The simultaneous daily administration of 50 mg/kg ganglioside mixture counteracted significantly this functional impairment, area and amplitude of the monophasic CAP being maintained closer to control values. These results suggest that the loss of functional nerve fibers can be reduced, in vincristine-induced neuropathy, by ganglioside treatment.

Action Potentials↗

ATPase activity defects in alloxan-induced diabetic sciatic nerve recovered by ganglioside treatment.

ATPase activities were measured in sciatic nerves from rats with alloxan-induced diabetes (ALX-D) of various duration (2 wk, 5 wk, 9 wk, and 6 mo). Our data confirm that sciatic nerve Na+-K+-ATPase abnormalities are present very early in ALX-D rats, similar to results previously described in streptozocin-induced diabetic rats, spontaneously diabetic BB Wistar rats, and ALX-D rabbits. Na+-K+-ATPase activity decreased by 26-47% in ALX-D rats compared with age-matched controls. Ganglioside treatment (10 mg/kg i.p. for 10 or 30 days starting 1 wk after ALX injection) completely impeded the enzyme reduction. The effect observed at the end of either 10 or 30 days of treatment lasted greater than or equal to 1 mo. Chronic diabetic groups treated for 30 days before killing also presented normal ATPase activity at the end of treatment. Therefore, gangliosides are effective on Na+-K+-ATPase even in animals with a longer duration of diabetes. The maintenance of fairly normal ATPase activity by ganglioside treatment could mirror a more general recovery from early metabolic dysfunction and/or late structural abnormalities in diabetic nerve fibers.

Alloxan↗

Unusual neurofibrillary accumulations induced by beta,beta'-iminodipropionitrile (IDPN).

Beta,beta'-iminodipropionitrile (IDPN) is a synthetic compound known to induce massive focal accumulations of neurofilaments almost exclusively in the proximal segments of motor and sensory axons. The present paper deals with a cat intoxicated with IDPN for five weeks. Swellings filled with skeins of maloriented neurofilaments were observed in the initial (non-myelinated) segment of intraparenchymal spinal axons in addition to the swellings consistently located in the first internodes. Filamentous masses in the initial segment were in some cases intermingled with focal accumulations of mitochondria and smooth vesicles to give the proximal axon the classical appearance of 'spheroid'. In some motoneurons, clumps of neurofilaments occupied the axon hillock and extended well into the perikaryon and some dendritic stems, making the borderlines between cell body and processes undistinguishable. Cytoplasmic organelles were displaced and rearranged in the presence of somal neurofibrillary changes. In a few neurons, regardless of the presence of swellings in the axon initial segment, signs of central chromatolysis were noticed, in the form of nuclear caps of Nissl substance and eccentricity of the nucleus. These findings are discussed with reference to other neurotoxic models of neurofibrillary pathology and the immunochemical differences recently detected between neurofilaments in perikarya, dendrites and axons.

Animals↗

[Colorectal tumors and hormonal receptors. A critical review of the literature].

The importance of sexual hormones in the development of cancers of the large bowel is strongly supported experimentally and epidemiologically. The clinical search for the presence of hormonal receptors in the cells of patients operated for tumours of the colon and rectum has been common since 1975. This investigation ought to have opened up new diagnostic and therapeutic prospects for these tumours which have given such a little curative satisfaction. The present review considered reported data. Unfortunately the emerging picture is irregular in cases and results. It is personally considered that these studies are not for the moment likely to produce important novelties for the treatment of tumours of the large bowel tract.

Colonic Neoplasms↗

Occurrence of lipofuscin pigment granules and "dense microspheres" in the spinal cord of young cats treated with beta,beta'-iminodipropionitrile (IDPN).

Spinal cords of cats treated with the neurotoxic compound beta,beta'-iminodipropionitrile (IDPN) were observed to contain rounded homogeneous bodies, 1-12 microns in diameter, termed "dense microspheres" (DMS). These bodies, absent in control animals, were consistently found only in the ventral horns. No relationship with blood vessels was evident. When stained with PAS and a modified von Kossa's silver nitrate technique, DMS remained negative, showing only very slight metachromasia in some toluidine blue-stained sections. They were consistently acidophilic as evidenced by destaining and differentiation investigations. DMS were observed more frequently in the proximity of nerve cell bodies or closely adjacent to dendrites and their location was mainly extracytoplasmic; with the electron microscope, however, some DMS were also found in glial processes. Rounded osmiophilic bodies, 0.1-0.8 microns in diameter, were noticed in mitochondria of both neurons and glial cells; however, whether they were special forms of DMS or different inclusions was not assessed. Both intra- and extracytoplasmic DMS were similar in ultrastructure, appearing as single membrane-bound spherical or pear-shaped bodies containing a cottony or finely granular matrix. Additionally, both perikaryon and processes of large motoneurons were found to contain pigment granules identified as lipofuscin, which seemed to increase in number and to spread centrifugally in the processes in correlation with duration of the intoxication and size of axonal swellings induced by IDPN.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Intranuclear inclusions in Schwann cells of aged fowl ciliary ganglia.

Schwann cells in ciliary ganglia of fowls aged five to seven years were found to contain numerous intranuclear inclusions and pseudo-inclusions. Similar inclusions were usually absent from both neurons and non-neuronal cells, including connective tissue cells, and were rare in Schwann cells of chickens aged less than five years. Inclusions were of two different types: filamentous bundles and granulofibrillar bodies. Individual nuclei contained one to three inclusions. Pseudo-inclusions, i.e. cytoplasmic pockets invaginated into the nuclei, were found more rarely and accompanied one or both types of 'true' inclusions. The possible significance of these findings in relation to ageing phenomena is discussed. It is concluded that intranuclear inclusions appear to be a consequence of nuclear/cellular activation and may be regarded as aggregates of previously dispersed intranuclear proteins.

Aging↗

Vasotocin fibers in the mesencephalon and pons of the domestic fowl. An immunohistochemical study.

Immunohistochemical analysis of the extrahypothalamic distribution of vasotocin-like immunoreactive elements within the brainstem of the domestic fowl revealed several, topographically identifiable, mesencephalic and pontine target areas. In the considered regions numerous nerve endings were surrounding perikarya or large dendritic trunks. No extrahypothalamic immunopositive perikarya have been observed in normal birds.

Animals↗