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Biomedical subjects

P Barone

Publications and source records attributed to P Barone.

At least 19 recordsLinked to original sources

Dopaminergic regulation of epileptic activity.

We evaluated the role of dopamine systems in the propagation of epileptic Focal, limbic seizures were produced by systemically administered pilocarpine (200 mg/kg, i.p.); as previously described this dose produces limbic stereotypes but neither convulsions nor seizure-related brain damage. The systemic pretreatment with D-1, but not D-2, agonists induced convulsions identical to those produced by a higher, convulsant dose of pilocarpine (400 mg/kg). Conversely, the pretreatment with D-1 receptor antagonists prevented the convulsions whereas the D-2 antagonists facilitated the pilocarpine-induced seizures. Furthermore, we studied the effects of intracerebral injections of dopamine agents on seizures induced by pilocarpine. Nigral microinjection of D-1 agonists strongly induced motor seizures in rats treated with the low dose of pilocarpine. On the other hand, microinjection of D-1 antagonists prevented the motor seizures induced by the high dose of pilocarpine. This study indicates that the two dopamine receptor subtypes, D-1 and D-2, exert opposing roles in the control of epilepsy propagation. Substantia nigra pars reticulata appears to be primarily involved in the dopamine-mediated modulation of seizures.

Animals

Prony-Householder method applied to 31P NMR signals: II. Study of conjugates of ara-AMP with lactosaminated albumin.

Conjugates of 9-beta-D-arabinofuranosyladenine 5'-monophosphate (ara-AMP) with lactosaminated albumin (L-SA), obtained by using two different coupling procedures, produce antibodies in rats and mice which display only a small cross-reactivity. 31P NMR signals from the two conjugates have been examined to clarify whether different lysine and histidine residues are involved in the two reaction pathways. The occurrence of different chemical shifts and linewidths between the two conjugates, as evidenced by processing the signals with the Prony-Householder method, indicates the formation of two different complexes.

Animals

Priming as a model of behavioural sensitization.

Repeated exposure to drugs acting as direct or indirect stimulants of central dopamine transmission results in sensitization to their behavioural stimulant properties (behavioural sensitization). Priming provides a simple model of behavioural sensitization particularly suitable for studies of its neural and molecular mechanisms. The results obtained to date indicate that priming results in an increased responsiveness of postsynaptic dopamine receptor mechanisms in the caudate nucleus, possibly due to an increased affinity of the D-1 receptor for its agonist.

Animals

Dopamine D1 and D2 receptors mediate opposite functions in seizures induced by lithium-pilocarpine.

The effect of selective dopamine receptor blockade on epileptic activity was tested in rats, using the lithium-pilocarpine seizure model. One day after lithium pretreatment, systemic administration of the dopamine D1 antagonist, SCH 23390, prevented the convulsive activity induced by either 10 or 15 mg/kg of pilocarpine in a dose-dependent manner as revealed by behavioral and electroencephalographic alterations. No anticonvulsant effect was observed when SCH 23390 was injected at the same time as lithium and 24 h prior to pilocarpine. Furthermore, the D2 antagonists, raclopride and haloperidol, potently reduced the threshold for convulsions induced by 10 mg/kg of pilocarpine, following lithium pretreatment. Neither dopamine D1 nor D2 antagonists altered the limbic stereotypies induced by pilocarpine, supporting the view that the dopamine system is primarily involved in the mechanisms of convulsion generation and seizure spreading. These results indicate that dopamine receptor subtypes exert opposite functions on the regulation of convulsive activity.

Animals

Immune response to simultaneous administration of a recombinant DNA hepatitis B vaccine and multiple compulsory vaccines in infancy.

The reactogenicity and immunogenicity of simultaneous administration of recombinant DNA hepatitis B vaccine with diphtheria and tetanus toxoids (DT) and oral poliovirus vaccine (OPV) in 111 infants were compared with those of DT and OPV alone in a control group of 21 infants. All subjects received three doses of the vaccine according to one of three different schedules of vaccination. Reactions following simultaneous administration of vaccines were all but absent, with mild pain reported for four out of 111 subjects, compared with one of 21 in the control group. Seroconversion rates of 98-100% and high anti-HBs geometric mean titres (GMTs) were observed in all study groups after three doses of hepatitis B vaccine. Significantly higher anti-HBs were seen in Group III, where six months is allowed between the second and the third hepatitis B vaccine doses, compared with Group I and II, where only 1-2 months separate the second and third doses. A fourth dose of vaccine was needed in both these groups to obtain anti-HBs levels as high as seen in Group III after three vaccine doses at 3, 4 and 10 months of age. The immune response to DT and OPV was similar in the study groups and the control group. It is concluded that a course of 10 micrograms doses of recombinant hepatitis B vaccine given simultaneously with DT and OPV elicits a strong anti-HBs response and does not interfere with the immune response to the other antigens.

Antibodies, Viral

Simultaneous administration of HB recombinant vaccine with diphtheria and tetanus toxoid and oral polio vaccine: a pilot study.

An extensive vaccination program to be used in highly endemic areas is the main strategy against the spreading of hepatitis B. The purpose of this study was the evaluation of the immune response to the recombinant HB vaccine administered singly or at the same time as other compulsory vaccines anti-diphtheria, anti-tetanus and oral anti-polio. Evidence was found of the serological efficacy both of HB vaccine and compulsory vaccines with a percentage of seroconversion of 100%. However, the infants who received HB vaccine at birth and at the age of 1 month had titers of antiHBs higher than the infants who received HB vaccine at birth and at 3 months. No difference in antibody levels of compulsory vaccines was observed among the study groups and the controls who received only compulsory vaccines. Our results suggest that HB vaccination must be encouraged and pursued in all newborns.

Diphtheria Toxoid

Effect of chronic D-1 and/or D-2 dopamine antagonist treatment on SKF 38393-induced non-stereotyped grooming.

The effects of chronic D-1 and/or D-2 dopamine (DA) receptor blockade on a putative D-1 DA receptor-mediated behavioral function was studied in rats treated for 21 days with the selective D-1 antagonist SCH 23390, the predominantly D-2 antagonist haloperidol, or the combination of both drugs at the same daily doses. Four days after the last drug dose, the non-stereotyped grooming response to the selective D-1 agonist SKF 38393 increased in SCH 23390-pretreated rats decreased in haloperidol-pretreated rats compared to controls, but remained unchanged in animals receiving both drugs. Underlying DA receptor changes and the resulting imbalance between D-1 and D-2 receptor presumably contribute to these effects, suggesting that the upregulation of one DA receptor subtype may modify the expression of behaviors associated with the other subtype.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben

Dopamine D1 receptor modulation of pilocarpine-induced convulsions.

The contribution of dopaminergic mechanisms to the generalization of epileptic activity was studied in rats given pilocarpine after pretreatment with selective dopamine agonists. At the dose of 200 mg/kg, pilocarpine produced limbic stereotypes but not convulsions or seizure-related brain damage. Pilocarpine, 200 mg/kg, following pretreatment with the D1 agonist (RS)-2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3 benzazepine, but not its (S)-enantiomer, induced convulsive activity as revealed by behavioral, electroencephalographic alterations and widespread brain damage. These features were identical to those produced by a higher, convulsant dose of pilocarpine (400 mg/kg). On the other hand, pretreatment with the D2 agonist 4,4a,5,6,7,8,8a,9-octahydro-5-n-propyl-2H-pyrazolo-3,4-g-quinoline failed to induce convulsions. Furthermore, the D1 receptor antagonist (R)-(+)-8-chloro-2,3,4,5-n-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine -7-ol prevented the convulsive activity induced by both 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3 benzazepine plus pilocarpine (200 mg/kg) and pilocarpine (400 mg/kg), given alone. However, neither dopamine agonists nor antagonists altered the limbic stereotypes induced by pilocarpine, suggesting a dopamine system involvement primarily in the mechanisms of epilepsy generalization. The results suggest that pharmacological manipulation of dopaminergic transmission may provide an alternative approach to therapy of secondarily generalized epilepsy.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben

Immune response of subjects at high risk of hepatitis B to a new genetically engineered hepatitis B vaccine administered in low doses by the intradermal route.

Fifty-eight subjects at high risk for hepatitis B were vaccinated with hepatitis B vaccine prepared by a DNA recombinant technique (Engerix B- Smith-Kline Biologicals) by the intradermal route with low doses (5 microgr) at 0, 15, 30 and 45 days on the volar surface of the arms. A positive immune response (100%) was found in all children (5 affected by thalassemia, 5 affected by sickle cell anaemia, 9 affected by neurological handicaps) and in all healthy medical staff. None showed side-effects and the small pigmented macula following vaccination disappeared after a few months. Since the World Health Organization proposed a program of mass vaccination in highly endemic areas for hepatitis B, the authors suggest that the use of the new engineered vaccine in low doses by the intradermal route could represent an effective strategy to realize this project.

Adolescent

Prefrontal cortex and spatial sequencing in macaque monkey.

1. Single neuron activity was recorded from the prefrontal cortex of two macaque monkeys during the performance of a task involving spatial sequencing. The monkeys faced a panel displaying a central fixation point and three fixed targets (two lateral and one above the point of fixation). In the first phase of each trial, the three targets were turned on in random order: in the second phase, the animal had to press each target, still lighted, in the order of their illumination. Thus, successful performance of the task depended strongly on temporal memory. The animals were fitted with DC-EOG electrodes. 2. Three hundred and two task-related neurons were recorded in the superior arcuate area and caudal part of sulcus principalis. Among the cells whose pattern of activity appeared to be related to the sequencing task, five classes were distinguished: Visual tonic (VT), fixation, context, saccade related and visual phasic cells. In addition, a small number of cells appeared to be related to other aspects of the behavior, but not to the sequencing task. Our present analysis concentrates on two groups of sequencing task-related cells (VT and context cells). 3. The VT cells (35/302-11.5%) were recorded exclusively from the superior arcuate area. All VT cells increased their firing rate (sustained activation) during fixation of the central fixation point (FP) following onset of one of the three targets used, specific for a given cell (directional or spatial selectivity). In one group of VT cells, a shift in the eye position towards the specific peripheral target resulted in the return of the cells' firing rate to the pre-trial level. In the other group of VT cells, reset of the firing rate to pre-trial level was not related to the onset of fixation of the peripheral target. Sustained activation of the VT cells depended also on the sequential order of illumination of the specific target (temporal selectivity). In twenty-four cells (68.5% of VT cells) sustained activation was observed when the target came first in the sequence. Onset of the target in the second or third rank elicited either no response or only a short lasting phasic activation. In the remaining eleven cells (31.5% of VT cells), sustained activation was only observed when the target came second in a given sequence. The firing of the VT cells was correlated with the animals' performance of the task.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Haloperidol- and SCH23390-induced dopaminergic supersensitivities are not additive in the rat.

The effect of chronic D-1 and/or D-2 dopamine receptor blockade on apomorphine-induced behaviors was studied in rats treated for 21 days with the selective D-1 antagonist SCH23390, the predominantly D-2 antagonist haloperidol, and the combination of the two drugs at the same daily doses (0.1 and 1 mg/kg respectively). Apomorphine (0.3 mg/kg) 4 days following the last injection of the drugs increased (49-70%) stereotypic behavior in all animals as compared to saline-treated controls. Although the SCH23390-induced increase was lower than haloperidol-induced supersensitivity, stereotypies after combined administration of both drugs did not differ significantly from either, suggesting that the effects of the two drugs are not additive. Underlying receptor changes and modified D-1/D-2 receptor interactions may account for the participation of both receptor subtypes to the development of neuroleptic-induced dopaminergic supersensitivity.

Animals

Comparison of electrocardiographic data (P waves): test of a shape-based approach.

We tested a method for comparing ECG signals (P waves), in a sample of 10 normal males. In each subject, sets of 219 body surface ECGs were simultaneously recorded during tidal respiration. Only beats at end expiration and peak inspiration were considered. The beats of each group were subdivided into two subgroups of the same size (about 30 beats) and separately averaged. The two averaged beats at end expiration, assumed to be equal, were compared in order to estimate the noise variance (sigma2), i.e., the lowest value of variance at which the beats were statistically similar (P less than 0.05). At the same value of sigma2, the beat at end expiration significantly differed from that at peak inspiration. By considering the individual leads, significant differences were found in more than 50% of the 219 ECGs, in specific thoracic areas. The data indicated that the method can reveal differences between P waves occurring during tidal respiration and provide information on the topographical distribution of the differences.

Adult

On the optimal choice of the electrode number and locations in body surface mapping.

The problem of choosing the number and the thoracic locations of the leads needed for reconstructing body surface maps of heart potentials is considered. In a previous work (P. Barone, In "Computers in Cardiology" (K. L. Ripley, Ed.), pp. 491-494. IEEE Computer Soc. Press, Washington, DC, 1985) the problem was solved, provided that the user is able to give a threshold below which the information content of two leads is considered equal. In this paper a sensitivity analysis that can help the user in choosing the optimal threshold, or, equivalently, the optimal number of leads, is performed. The problem is reduced to the dynamic search of spanning forests of an undirected graph. An example using real data is also discussed.

Algorithms

Role of the dorsolateral prefrontal cortex in organizing visually guided behavior.

Unit activity was recorded in the prefrontal cortex of rhesus monkeys during performance of a delayed task with two motor responses, a saccade and an arm movement, to a complex pattern of auditory and visual stimuli. The peculiarity of the paradigm was that onset of the different sensory stimuli, orienting saccade and arm movement, were dissociated in time and occurred at prefixed time intervals. Two hundred and sixteen task-related units were recorded. The data show that the dorsolateral part of the prefrontal cortex plays a crucial role in temporal organization of visually guided behaviour. This cortical area contains the neural substrate of an encoding strategy for remembered or current events and objects in the behavioural surround that are not, as yet, foveated. This encoding mechanism subserves a particular cognitive process. Whether events or objects are, or are not, encoded depends on their significance for future behaviour. While foveation deletes their neural trace, it activates a class of cells that appear involved in the preparation of arm movements towards the foveated region. The destruction of these two complementary mechanisms would disrupt the organism's capacity to integrate temporally and spatially discontinuous information for performance of goal-directed acts.

Animals

D-1 dopamine agonist administration reduces the threshold for convulsions produced by pilocarpine.

Focal, limbic seizures were produced by systemically administered pilocarpine (200 mg/kg, i.p.); as previously described this dose produces limbic stereotypies but neither convulsions nor seizure-related brain damage. The pretreatment, 5 minutes prior pilocarpine, with the D-1 agonist SKF 38393 (-ED50 = 1 mg/kg; i.p.) induced convulsions similar to those produced by a higher, convulsant dose of pilocarpine. On the other hand, the pretreatment with the D-2 agonist LY 171555 failed to induce convulsions. The D-1 receptor antagonist SCH 23390 prevented the convulsions induced by SKF 38393 plus pilocarpine (200 mg/kg). This study indicates that D-1, but not D-2, receptor stimulation converts subconvulsant doses of pilocarpine into convulsant ones.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben