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Biomedical subjects

P Ferrero

Publications and source records attributed to P Ferrero.

47 records · Page 3Linked to original sources

A brain octadecaneuropeptide generated by tryptic digestion of DBI (diazepam binding inhibitor) functions as a proconflict ligand of benzodiazepine recognition sites.

An octadecaneuropeptide (ODN) produced by the tryptic digestion of DBI was purified and sequenced and its activity on the Vogel test determined. In vitro ODN displaces 3H-diazepam from specific brain recognition sites and injected intraventricularly in thirsty rats facilitates the onset of behavioral inhibition elicited by punishment. The alpha-amide derivative of ODN is devoid of either action. Evidence is presented suggesting that DBI sequence includes at least two replicas of ODN or one replica of ODN and a fragment with similar if not identical amino acid sequence but identical biological activity.

Amino Acid Sequence↗

Increase in the Bmax of gamma-aminobutyric acid-A recognition sites in brain regions of mice receiving diazepam.

gamma-Aminobutyric acid (GABA) receptors were characterized in vivo by studying ex vivo the binding of [3H]muscimol to cerebellum, cortex, hippocampus, and corpus striatum of mice receiving intravenous injections of tracer doses of high-specific-activity (approximately equal to 30 Ci/mmol) [3H]muscimol. This ligand binds with high affinity (apparent Kd, 2-3 X 10(-9) M) to a single population of binding sites (apparent Bmax, 250-180 fmol per 10 mg of protein). Pharmacological studies using drugs that selectively bind to GABAA or GABAB receptors suggest that [3H]muscimol specifically labels a GABAA recognition site. Moreover, diazepam (1.5 mumol/kg, i.p.) increases the Bmax but fails to change the affinity of [3H]muscimol binding to different brain areas. This diazepam-elicited increase in Bmax is blocked in mice receiving the diazepam antagonist Ro 15-1788 (ethyl-8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5a]-[1,4] benzodiazepine-3-carboxylate). Since the diazepam-induced increase of [3H]muscimol binding is paralleled by a significant potentiation of the inhibitory effect of muscimol on locomotor activity, it is proposed that the facilitatory action on GABAergic transmission elicited in vivo by diazepam is mediated by an increase in the Bmax of the binding sites of GABAA receptors.

Animals↗

Neonatal hypoxia and epileptic risk: a clinical prospective study.

A historical cohort study was undertaken to determine the risk of epilepsy in a population of 371 newborns with an acute neurological disorder related to fetal and/or neonatal hypoxia compared with a control population of 362 normal newborns. The results showed that the risk of epilepsy was 5.1 times higher in the group of subjects affected at birth by a hypoxia-related acute neurological syndrome than in the control group. (Although the incidence of epilepsy is higher in the first year of life, epileptic seizures connected to perinatal hypoxia may occur in early childhood or later on.) Also, there were frequently persistent neuropsychiatric disorders in children with perinatal hypoxia (5.4%). There was no difference in the two groups regarding the incidence of febrile convulsions. The data show that perinatal hypoxia plays a role in the etiology of epilepsy, although at birth the hypoxia might result in only a modest and oftentimes completely reversible neurological syndrome.

Asphyxia Neonatorum↗

In vivo modulation of brain dopamine recognition sites: a possible model for emission computed tomography studies.

The content of authentic 3H-spiroperidol and of its metabolites was measured in brain regions of rat, guinea pig and mouse receiving tracer doses of 3H-spiroperidol intravenously (0.2 to 0.5 micrograms/kg). The time course of the 3H-spiroperidol content of various brain regions shows that a steady state was maintained between 2 and 6 hrs; the lowest 3H-spiroperidol content was attained in cerebellum where the value approached that of blood plasma. Since the cerebellum contains an insignificant number of dopamine receptors but many serotonin receptors and other sites that bind 3H-spiroperidol, the 3H-spiroperidol contained in cerebellum was considered background binding. In the striatum and olfactory tubercle of rats receiving two daily doses for 3 weeks of haloperidol or amphetamine the amount of 3H-spiroperidol that binds in vivo is decreased or increased, respectively. If the kinetic characteristics of in vivo binding of 3H-spiroperidol observed in the rat, guinea pig and mouse can be replicated in man using spiroperidol containing a gamma- or a position-emitting label, one might have a probe to study dopamine receptors in vivo with emission computed tomography scanning.

Animals↗

Brainstem auditory evoked potentials in postconcussion syndrome.

Brainstem auditory evoked potentials (BAEPs) were recorded from 55 patients with postconcussion syndrome (PCS) to elicit evidence of an organic and subclinical brainstem disorder. Fifteen patients (27.3%) showed abnormal responses unilaterally or bilaterally, especially for one or more interpeak latencies prolonged beyond the upper 99% confidence limits. Other 9 patients had borderline responses. The BAEP alterations were not correlated either with dizziness at the time of recording, or with vestibular troubles in the routine caloric test. Though BAEP abnormalities may be present a long time after injury, we found an improvement of responses in the majority of 14 re-tested patients. These data show that BAEP can give an objective demonstration of a reversible brainstem disorder in patients with PCS.

Adolescent↗

Acute neurologic complications of hemodialysis. Study of 14,000 hemodialyses in 103 patients with chronic renal failure.

We have examined and subjected to statistical analysis the transient acute neurological complications arising in the course of hemodialysis in 103 patients with chronic renal failure (13,969 hemodialysis sessions). Our data show that such complications are multiform. Some of the symptoms are aspecific: headache, nausea and/or vomiting, muscle cramps. We have found these symptoms in over 96% of patients, often combined with extraneurological symptoms and phenomena, such as cardiocirculatory shock or increased blood pressure. The other symptoms denote real cerebral impairment: convulsions, consciousness disturbances, psychomotor agitation. They are present in 36% of the patients, but only 10.5% of the patients show a combination of at least two symptoms. In these patients the so-called "Disequilibrium syndrome" is present: its percentage in our case-series is similar to that reported in literature.

Adolescent↗

Peripheral-type benzodiazepine receptors and diazepam binding inhibitor-like immunoreactivity distribution in human peripheral blood mononuclear cells.

Peripheral-type benzodiazepine receptors (pBZr) in human lymphocytes have been detected only in mixtures of peripheral blood mononuclear cells (PBMC). The present investigation was designed to describe precisely the location of pBZr in the various sets and subsets of PBMC, purified using monoclonal antibodies to specific PBMC surface markers. Site densities and affinities of pBZr were measured in the intact cells by conventional binding, using 3H-PK 11195 as a ligand. Moreover, we used a specific radioimmunoassay to identify in these cells the presence of the polypeptide diazepam binding inhibitor (DBI), a putative endogenous ligand for various benzodiazepine receptors including the peripheral type. Two major findings are derived from these studies: first, the coexistence of pBZr and DBI, or closely related immunoreactive material, in all major lymphocyte sets and subsets, as well as in monocytes. And second, the significant correlation (r = 0.87, p < 0.001) observed between the density of pBZr in a given cell type and its abundance of DBI like-immunoreactivity (DBI-LI). For both pBZr and DBI-LI content the cell distribution was monocytes > B cells and large granular lymphocytes > T cells (CD3+ set or CD4+ and CD8+ subsets) (ANOVA: pBZr: F = 114.11, p < 0.001; DBI-LI: F = 20.79, p < 0.001). The results are discussed in terms of the possibility that DBI and pBZr might share a relevant interaction in immunocompetent elements, thereby contributing to a new route of connection between the immune and the nervous systems.

B-Lymphocytes↗

Coronary reactive hyperaemia after two periods of coronary occlusion in the anaesthetized goat.

In the coronary circulation an ischaemic preconditioning obtained with two periods of 2.5 min each of occlusion of the left circumflex coronary artery alters the pattern of a coronary reactive hyperaemia which follows 15 s only of occlusion of the studied artery. The most remarkable change consists of a reduction of 40-45% of the time required by the flow to reach the maximum hyperaemic peak (time to peak) after the brief occlusion. The present investigation was planned to study whether the time to peak of the hyperaemia following the second 2.5 min preconditioning occlusion was shorter than the hyperaemia following the first occlusion. Experiments performed in the anaesthetized goat, in which coronary flow was measured with an electromagnetic flow-probe placed around the left circumflex coronary artery showed that in the hyperaemia occurring after the second preconditioning occlusion the time to peak was reduced by 18% only. The moderate effect of the second preconditioning occlusion in reducing the time to peak is attributed to the fact that the heart was already partially preconditioned after the first occlusion and that after relatively long periods (2.5 min) of occlusion the metabolic component of the hyperaemic response was so predominant to partially mask the role of the vascular mechanisms presumably responsible for the reduction of the time to peak.

Animals↗