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Biomedical subjects

G Gandolfo

Publications and source records attributed to G Gandolfo.

At least 19 recordsLinked to original sources
PubMed1991

Riluzole prevents hyperexcitability produced by the mast cell degranulating peptide and dendrotoxin I in the rat.

Using electroencephalographic (EEG) recordings in freely moving rats and extracellular neuronal firing-rate recordings in hippocampal slices, we examined the effects of riluzole (RP 54274), a compound with anti-glutamate properties, against the convulsive seizures and the cellular hyperexcitability produced by the mast-cell degranulating peptide (MCD), dendrotoxin I (DTXi) and 4-aminopyridine (4-AP). I.c.v. administration of riluzole (10 nmol) prevented the seizures induced by MCD, and to a lesser extent those due to DIXi, whilst leaving 4-AP seizures unaffected. This effect was also present after oral administration of the compound (4 mg kg-1) and lasted for approximately 6 h. Electrophysiological recordings in vitro confirmed that riluzole dose dependently and reversibly abolished the sustained increase in firing rate induced by both MCD and DTXi in the hippocampus. These results indicate that the anti-epileptic spectrum of riluzole in this model has similarities with, but is not identical to, that of classical potassium channel openers, and differs from that of calcium channel blockers or other glutamate antagonists such as D(-)-2-amino-5-phosphono-valeric acid. However, since MCD releases glutamate, the preventive effect of riluzole in this model may involve direct or indirect interaction with glutamatergic processes.

4-Aminopyridine↗
PubMed1991

Thymopentin and interleukin-2 in combination with 5-fluorouracil and leucovorin in metastatic colorectal adenocarcinoma: preliminary results.

Thymic hormones have been shown to exhibit immunorestorative effects in vivo and in vitro, and to enhance the expression of high affinity interleukin-2 (IL-2) receptors on normal human lymphocytes stimulated with phytohemagglutinin. Based on these data, a clinical trial was initiated to determine the effects of the combination of 5-fluorouracil (5-FU) and folinic acid (FA) with thymopentin (TP-5) and interleukin-2 (IL-2) in patients with advanced colorectal carcinoma. Fifteen patients were treated with FA, 200 mg/m2/day by IV bolus, and 5-FU, 400 mg/m2/day as a 30-minute infusion, both given for 5 consecutive days every 28 days. TP-5, 50 mg/day, was administered subcutaneously on days 8-11, and IL-2, 9 million IU/m2 twice daily, was given subcutaneously on days 12-16. Of 8 patients evaluable for response, 4 achieved a response. Two patients had stable disease, and two progressed during treatment. There were no instances of life-threatening toxicity. Two patients developed grade III stomatitis and diarrhea followed by leukopenia and fever, requiring hospitalization. Other toxicities were moderate. These results are only preliminary, and a larger number of patients and longer follow-up are needed to draw meaningful conclusions about the merits of this new approach in cancer treatment.

Adenocarcinoma↗
PubMed1990

Genetically epileptic rats show a pronounced intermediate stage of sleep.

Rats of the genetically epileptic WAG/Rij strain show a more long-lasting intermediate stage of sleep compared to rats of the Wistar strain. Therefore the WAG/Rij strain provides a privileged model for studying this stage of sleep. On the other hand, the percentage of paradoxical sleep in WAG/Rij rats is lower than in Wistar rats, for the reason that the intermediate stage in WAG/Rij rats is less frequently followed by paradoxical sleep and more frequently by slow wave sleep and especially by arousals. It is speculated that the epileptic rats encounter a greater difficulty in entering into paradoxical sleep.

Animals↗
PubMed1989

Analogies and differences in the mode of action and properties of binding sites (localization and mutual interactions) of two K+ channel toxins, MCD peptide and dendrotoxin I.

Both the bee venom toxin, mast cell degranulating (MCD) peptide, and the snake toxin, dendrotoxin 1 (DTX1) induce epileptiform activity and paroxystic seizures after intracerebroventricular (i.c.v.) injection to rats. Although many of the properties of the two toxins, which are blockers of the same K+ channel, appear to be very similar, a number of differences have been found. (1) Induced seizures have an hippocampal origin for MCD and two different origins, situated in the cortex and in the limbic system, for DTX1. (2) A first i.c.v. administration of DTXI desensitizes against a second ipsilateral injection of the same peptide as we had previously observed for MCD. However no cross-desensitization was observed between the two different toxins. (3) The number of high affinity (Kd = 41 pM) binding sites for 125I-DTXI in synaptic membranes is about 5 times higher than the number of high affinity (Kd = 158 pM) binding sites for 125I-MCD. (4) Autoradiographic analysis of the distribution of high affinity 125I-DTX1 binding sites has been compared to our previous analysis of high affinity 125I-MCD binding sites. High levels of high affinity binding sites for both toxins seem to be localized in synapse-rich areas. However high affinity binding sites for the two toxins are not always co-localized. Analysis of the mutual interactions between DTXI and MCD binding sites has revealed the presence of classes of low affinity binding sites for MCD. In most areas of the brain, a large proportion of high affinity binding sites for DTXI is allosterically related to low affinity binding for MCD.

Animals↗
PubMed1989

Subtypes of K+ channels differentiated by the effect of K+ channel openers upon K+ channel blocker-induced seizures.

Intracerebroventricular injection of mast-cell degranulating peptide (MCD), dendrotoxin I (DTXI) and 4-aminopyridine (4-AP), 3 blockers of a subclass of K+ channel, produces seizures and convulsions. Three different K+ channel openers are potent blockers of MCD-induced hyperexicitatory effects when they are administered preventively but they are unable to inhibit the epileptogenic effects induced by DTXI and 4-AP which were thought to block the same K+ channel which is blocked by MCD.

4-Aminopyridine↗
PubMed1989

Ca2+ channel blockers prevent seizures induced by a class of K+ channel inhibitors.

Intracerebroventricular injection into rats of mast-cell degranulating peptide (MCD), dendrotoxin I (DTXI) and 4-aminopyridine (4-AP), three blockers of a subclass of K+ channels, elicited epileptiform wave bursts and convulsions. Three different types of L-type Ca2+ channel inhibitors (+)PN 200-110, a 1,4-dihydropyridine, (-)D888, a phenylalkylamine, and fluspirilene, a diphenylbutylpiperidine, were potent blockers of the convulsant-induced hyperexcitatory effects when they were administered preventively. D-AP5, a N-methyl-D-aspartate antagonist, was active on the 4-AP-induced seizures but was without effect on the MCD- and dendrotoxin-induced seizures.

4-Aminopyridine↗
PubMed1989

Hippocampal theta activity in the acute precollicular rat.

In eleven acute precollicular rats, cortical and hippocampal EEG activity was recorded. Hippocampal theta activity of low frequency (mean 4.5 c/sec) was found in nine rats and in four occupied above 50% of the recording time. In contrast, in the cortex the synchronized EEG activity dominated. The electrical stimulation of the posterior hypothalamus induced the theta rhythm, or increased its frequency. The large amounts of theta activity in some rats suggests that the forebrain theta pacemakers, partly modulated by the posterior hypothalamus, are released from brain stem inhibitory influences.

Animals↗
PubMed1988

Fetal serotoninergic transplants in the fourth ventricle of adult rodents reverse sleep disturbances induced by neonatal administration of 5,7-dihydroxytryptamine.

Rats received a neonatal (at 4 days of age) intracisternal injection of 5,7-dihydroxytryptamine which eliminates serotonin (5-HT) throughout adulthood. Sleep recordings, performed on these rats at adult age, demonstrated significant decreases in paradoxical sleep. Dissociated fetal 5-HT cell suspensions transplanted in the IVth ventricle of these rats restored paradoxical sleep. However, fetal neuronal noradrenergic or cholinergic transplants did not restore paradoxical sleep. These results suggest that paradoxical sleep is directly or indirectly mediated through serotoninergic mechanisms.

5,7-Dihydroxytryptamine↗
PubMed1988

Automatic sleep-wake scoring in the rat on microcomputer APPLE II.

An automatic scoring system in real time of sleep-wake behavior in the rat was elaborated on microcomputer APPLE II. Four electrophysiological recording channels were used to distinguish seven behavioral states. Because the rat shows behavioral stages which are short-lasting, the analysis is performed second by second. It is based on the detection of the signal energy in specific frequency bands. The percentage of time passed in each stage is computed every 15 min, 1 h, 6 h and 24 h, the analysis extending during several days without interruption. The data are also printed out in a listing in real time and histograms in batch mode. Because of the interindividual differences, a calibration is needed. It is performed with a program in batch mode which allows an adjustment of parameters of determination from given specific digitized sequence in each rat. The accuracy of the automatic method was tested by the C contingency test, the theoretical maximal level being at 0.93: the intra- and inter-researchers contingency was 0.89, that between researchers and the computer was 0.85.

Animals↗
PubMed1988

Incidence and prognostic significance of autoantibodies against erythrocytes and platelets in chronic lymphocytic leukemia (CLL).

Antiglobulin Test (AT), and Dixon Tests (DT) have been studied in 100 patients with CLL. Thirty-five patients were Rai stage 0 and I, 19 patients stage 2, 13 patients stage 3 and 33 patients stage 4. Twelve patients showed a Red Blood Cells Autoantibodies (RBCAb) positivity; a positivity (direct, indirect, or both) of DT was present in 74% of patients. The presence of autoantibodies against erythrocytes and platelets did not influence survival curves, but anemia and thrombocytopenia are risk factors for survival, independently of the presence of an autoimmune disorder. Nine patients RBCAb positive and DT positive showed the worst survival curve, five out of these were anemic and one thrombocytopenic and anemic.

Aged↗
PubMed1987

The brain response to the bee venom peptide MCD. Activation and desensitization of a hippocampal target.

The mast cell-degranulating peptide (MCD) isolated from bee venom has been found previously to have receptor sites in rat brain. Behavioral and electrocorticographic responses following intracerebroventricular injections of various doses of MCD have been analyzed. MCD produced a quasi-permanent hippocampal theta rhythm in the motionless animal alternating with epileptiform spike waves and paroxystic seizures. At a dose of 70 pmol seizures occurred for half of the treated rats. At a dose of 100 pmol generalized paroxystic crises were observed for all the rats. These effects were not antagonized by naloxone, morphine, diazepam and progabide. Rats recovered 24 h after a 100 pmol injection of MCD. A second ipsilateral injection to these rats showed the occurrence of a desensitization phenomenon. Desensitization was not observed when the second injection was contralateral. These physiological responses were studied in relation with a biochemical approach on membrane sites of action of MCD using [125I]MCD and their behavior in the desensitization process. The target of [125I]MCD is the ipsilateral hippocampus. Recovery from MCD effects was not due to MCD degradation. Desensitization was not due to down-regulation of the MCD receptor level.

Animals↗
PubMed1986

Statistical argument for a presynaptic origin of the second positive component of somesthetic primary cortex evoked potential elicited by central afferent stimulation.

The positive components 1 and 2 of the averaged field response induced in the somesthetic S1 cortex by submaximal stimulation of cortical radiation and supramaximal stimulation of lemniscus medialis showed non-existent amplitude variability whereas the dispersion was significant for components 3, 4 and 5. The same stimulus delivered at a short intershock interval only induced waves 1 and 2 without any amplitude variability, the three following ones being under complete refractoriness. These results suggest a presynaptic origin of component 2.

Animals↗
PubMed1986

[Neonatal administration of 5,7-dihydroxytryptamine induces in the adult rat a decrease in paradoxical sleep restored by an intracisternal injection of fetal raphe cells].

By a method of automatic on-line scoring of sleep-waking stages in the rat, a significant decrease of the mean circadian level of paradoxical sleep and a significant increase of light slow sleep were shown in adult animals after neonatal disruption of serotoninergic system by intracisternal injection of 100 micrograms of 5.7-dihydroxytryptamine, when compared to an aged matched sham group. The level of paradoxical sleep was restored in the neurotoxin-treated rats by an intracisternal injection of a suspension of foetal raphe neurons.

5,7-Dihydroxytryptamine↗
PubMed1986

A massive but short lasting forebrain deafferentation during sleep in the rat and cat.

The rat and cat show just prior and sometimes after paradoxical sleep a short-lasting behavioral stage characterized by: i) frontal cortex high amplitude spindle bursts and low frequency theta activity in the dorsal hippocampus, and ii) the lowest ventrobasal complex transmission level of all sleep-waking stages. The duration of this "intermediate" stage is increased at the expense of paradoxical sleep by low doses of barbiturate. The intercollicular "cerveau isolé" preparation shows for hours the electrophysiological patterns of the intermediate stage. It is concluded that the intermediate stage of sleep corresponds to a forebrain massive deafferentation process leading to a functional disconnecting from the brainstem. For the survival of the species it is understandable that this behavioral stage is necessarily short lasting.

Animals↗