Biomedical subjects

A Loizzo

Publications and source records attributed to A Loizzo.

At least 55 records · Page 3Linked to original sources

PubMed1994

Visual, auditory, and somatosensorial evoked potentials in early and late treated adolescents with phenylketonuria.

Pattern reversal visual, auditory, and somatosensorial evoked potentials were recorded in two groups of phenylketonuric (PKU) adolescents after protracted exposition to high concentrations of phenylalanine following diet discontinuation. The first group consisted of 11 early treated (before age 3 months) PKU patients (ET-PKU); the second group consisted of 11 late detected (after age 8 months), symptomatic, PKU subjects (LT-PKU). Despite the relevant lag between the two groups in mental development and neurological status, no clear-cut difference in evoked potentials could be detected. Only the wave I latency of the brainstem auditory evoked potentials (BAEPs) was significantly shorter in ET- versus LT-PKU children. The P100 latency, I-V interpeak latency (IPL), and I-III IPL seem to discriminate the less severe form of PKU (ET-PKU type 3) from the most severe forms, ET-PKU type 1 plus 2 and LT-PKU. No correlations were found between clinical, biochemical, and neurophysiological parameters. The present data suggest that evoked potentials technique is of limited sensitivity in detecting central nervous system (CNS) alterations in PKU adolescents after diet discontinuation.

Adolescent↗

PubMed1994

Dexamethasone-induced selective inhibition of the central mu opioid receptor: functional in vivo and in vitro evidence in rodents.

1. Endogenous corticosteroids and opioids are involved in many functions of the organism, including analgesia, cerebral excitability, stress and others. Therefore, we considered it important to gain information on the functional interaction between corticosteroids and specific opioid receptor subpopulations. 2. We have found that systemic administration (i.p.) of the potent synthetic corticosteroid, dexamethasone, reduced the antinociception induced by the highly selective mu agonist, DAMGO or by less selective mu agonists morphine and beta-endorphin administered i.c.v.. On the contrary dexamethasone exerted little or no influence on the antinociception induced by a delta 1 agonist, DPDPE and a delta 2 agonist deltorphin II. Dexamethasone potentiated the antinociception induced by the kappa agonist, U50,488. 3. In experiments performed in an in vitro model of cerebral excitability in the rat hippocampal slice, dexamethasone strongly prevented both the increase of the duration of the field potential recorded in CA1, and the appearance and number of additional population spikes induced by mu receptor agonists. 4. In both models pretreatment with cycloheximide, a protein synthesis inhibitor, prevented the antagonism by dexamethasone of responses to the mu opioid agonists. 5. Our data indicate that in the rodent brain there is an important functional interaction between the corticosteroid and the opioid systems at least at the mu receptor level, while delta and kappa receptors are modulated in different ways.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1994

Dexamethasone and hormones related to the hypothalamic-pituitary-adrenal axis modulate inherited neocortical spindling in DBA/2J mice.

The role of dexamethasone and hormones related to the hypothalamic-pituitary-adrenal (HPA) axis (corticotropin-releasing factor, adrenocorticotropic hormone, corticosterone) in the control of the spike-and-wave spindling episodes (S&W) which can be spontaneously recorded in the electrocorticogram (ECoG) of DBA/2J mice was investigated. Both dexamethasone and hormones related to the HPA axis consistently reduced the S&W in DBA/2J mice. Cycloheximide (a protein synthesis inhibitor) pretreatment significantly delayed the reducing effect of dexamethasone on the S&W in mice. After a transitory decrease, the glucocorticoid receptor antagonist RU-38486 induced a dramatic increase in the rate of the S&W episodes. In addition, mice treated with RU-38486 for 4 days showed a significant increase in the S&W 24 h after the 4th treatment. Our results indicate that dexamethasone as well as hormones related to the HPA axis are able to modulate the S&W in DBA/2J mice, suggesting that this effect may be bound to corticosteroid activity. The time lag (30-60 min) which is necessary for revealing the reducing influence of dexamethasone on the S&W in mice and the influence exerted by cycloheximide on dexamethasone activity support the hypothesis that the effect induced by dexamethasone may be at least in part dependent on genomic mechanisms.

Adrenocorticotropic Hormone↗

PubMed1994

Subchronic treatment with fragments of beta-endorphin prevents electroencephalographic seizures and behavioral alterations induced by centrally administered beta-endorphin in the rabbit.

The effects of some beta-endorphin fragments with neuroleptic-like properties, i.e., tau-endorphin, des-tyr1-tau-endorphin (DT tau E), desenkephalin-tau-endorphin (DE tau E), in comparison with the dopaminergic antagonist haloperidol,- were studied on the EEG and behavioral alterations induced by beta-endorphin in the rabbit. beta-Endorphin administered i.c.v. (5-30 nmol) induced EEG nonconvulsive limbic seizures as well as EEG background and behavioral alterations which were antagonized by naloxone administered i.v. (1-2 mg/kg). Haloperidol, tau-endorphin, DT tau E and DE tau E were unable to prevent beta-endorphin-induced alterations when injected in a single dose i.v. (25-50 micrograms/kg), 15 min before beta-endorphin. Subchronic i.v. administration of DT tau E or DE tau E (25 micrograms/kg/day) for 4 consecutive days prevented completely EEG limbic seizures as well as EEG background and behavioral alterations induced by i.c.v. beta-endorphin injected 15 min after the fourth dose; however, haloperidol (30 micrograms/kg/day) administered with the same schedule as DT tau E or DE tau E was able to prevent only EEG epileptiform and EEG background alterations induced by beta-endorphin. tau-Endorphin administered i.v. for 4 consecutive days (25 micrograms/kg/day) did not consistently influence any of the beta-endorphin effects. Our results show that DT tau E and DE tau E, which are devoid of opioid activity, exert a strong antagonism on ictal seizures as well as on other EEG alterations and behavioral alterations induced by beta-endorphin, and suggest that the antagonism shown by these drugs and by haloperidol on the EEG effects induced by beta-endorphin are exerted at least in part through an indirect action, i.e., an interaction with the dopaminergic system.

Animals↗

PubMed1993

Differential sensitivity to dexamethasone influence on morphine antinociception in two different strains of mice: DBA/2J and C57BL/6.

The influence of dexamethasone on morphine antinociception in two different strains of mice (DBA/2J and C57BL/6) was studied by using the hot plate test. Intracerebroventricular (i.c.v.) injection of dexamethasone induced a significant increase of nociceptive response in DBA/2J but not in C57BL/6 mice. Intraperitoneal (i.p.) injection of dexamethasone did not modify nociceptive response both in DBA/2J and C57BL/6 mice. Both i.c.v. and i.p. injection of dexamethasone did not modify morphine antinociception in DBA/2J mice whereas a significant reduction of morphine antinociception was observed in C57BL/6 mice after i.p. injection of dexamethasone. These results suggest that the use of different genetic strains may provide an useful approach for studying dexamethasone-morphine antinociception interaction.

Animals↗

PubMed1993

Reduced antinociceptive response to beta-endorphin in adult mice after chronic neonatal handling.

Male CD-1 mice were daily exposed to handling stress from second to the nineteenth days of life. Eleven and 16 days after the interruption of stress, handled (HA) and control nonhandled (UHA) animals were tested to measure the baseline threshold for the perception of thermal nociceptive stimulation by the tail-flick test (TFT) and to assess the presence of the Straub tail response (STR). On day 50 of life, the antinociceptive response induced by intracerebroventricular B-endorphin (BE) was also studied. The results indicated that animals chronically handled during the neonatal period, at the age of 5 weeks, showed a strong activation of the endogenous opioid system as demonstrated by the higher response latency to the TFT, as well as by the presence of a marked STR. Then, at the age of 50 days, there was no longer a difference in the TFT latencies between UHA and HA groups, but a significantly reduced response to the antinociceptive effect of BE was present in HA mice.

Animals↗

PubMed1993

Des-tyrosine-gamma-endorphin effects on morphine analgesia in mice.

1. The effects that were induced by a beta-lipotropin fragment des-tyrosine-gamma-endorphin (DT gamma E) devoid of opiate activity that was administered intraperitoneally or intracerebroventricularly to mice under morphine analgesia were investigated. The interaction of this peptide with the analgesic effects of morphine was examined using the hot plate and the tail flick test. 2. Intraperitoneal acute treatment with DT gamma E did not change the analgesic effects of morphine. 3. Intraperitoneal semi-chronic treatment performed for 4 days with DT gamma E enhanced morphine analgesic effects. 4. The intracerebroventricular acute treatment with DT gamma E reduced morphine analgesia in a dose-dependent way. 5. These results indicate that DT gamma E, although devoid of opioid activity per se, may interact with the opioid system, probably through an indirect mechanism.

Analgesics↗

PubMed1993

Opioids and corticosteroids involvement in the regulation of the neocortical spindling episodes in DBA/2J mice.

The present study examined the effects of dexamethasone and RU-38486 on the spike-and-wave spindling episodes (S&W) which can be spontaneously recorded in the electroencephalogram (EEG) of DBA/2J mice. Our data indicated that dexamethasone (1-10-100 micrograms/kg, ip) in a time- and dose-related manner significantly reduce the S&W occurrence in freely-moving DBA/2J mice. Cycloheximide (10 mg/kg, ip), a protein synthesis inhibitor, by itself did not modify significantly the S&W occurrence in mice, but when injected two hours before DEX (100 mg/kg, ip), induced consistent delay of DEX effects. On the other hand, treatment of mice with RU-38486 (50 mg/kg, ip) induced, after a transitory decrease, a dramatic increase of the rate of S&W episodes. In addition, we performed a "chemical adrenalectomy" treating mice with RU-38486 (50 mg/kg, po/d) for 4 days, and also in this case we observed a significant increase of S&W 24 h after the 4th treatment. Finally a series of experiments indicated that low doses of morphine inhibited, whereas high doses of naltrexone strongly enforced S&W. The present results suggest that glucocorticoids are able to modulate inherited spindling episodes in DBA/2J mice and that this effect may be related to a genomic activation mechanism. Studies in this field may give, in the near future, some important contributions to the understanding of corticosteroids involvement in brain excitability, and of their relationships with the opioid system.

Adrenal Cortex↗

PubMed1993

[Orphan diseases].

Basic investigation in industrial laboratories are mainly addressed to widespread diseases. It follows that: 1) basic research is addressed chiefly to the well known and largely diffuse diseases; 2) rare diseases are not usually studied and therefore little chance is given to their physiopathological or therapeutic knowledge. Hence the name of orphan diseases. The aim of this study is to contribute to the stimulation of innovative and applied basic research of orphan diseases and therefore to gradually confine the number of incurable rare diseases. Our proposal upsets the studies undertaken in some foreign countries and Italy on the orphan drugs (e.g. Orphan Drug Act, issued in the USA in 1982) since we suggest starting from a study on disease more than studies on drug. The planning of studies of disease may be undertaken on various points of view (prevalence, clinical features, prognosis, social cost, etc.), while this may be very hard for the drug. Therefore we suggest starting from a study plane, classification and estimation of rare diseases, shared for apparatus. These studies may be undertaken on a vigorous rationale (more than studies on orphan drugs) and therefore they may bring about to the definition of a national (government) planning for addressing consistent financial resources to the study of pathophysiology and therapy (or prevention) of the major orphan diseases. Adequate studies within the European Community may be planned in the near future, since most rare diseases are presumed to have a common distribution within the Community.

Disease↗

PubMed1992

An EEG analysis of drug effects after mild head injury in mice.

An electroencephalographic (EEG) and behavioral model of head injury in unanesthetized, free moving mice has been used to test the effects of TRH and GM1. In our experimental conditions a mechanical head injury capable of inducing loss of righting reflex for 2 to 60 sec, also induces a consistent decrease of the total power of the spectrum of EEG and a decrease of the power of fast beta band (20-40 Hz) for at least 120 min. TRH, injected after trauma in dose of 10 mg/kg, caused improvement of EEG total power of the spectrum. GM1 in high (30 mg/kg) but not in low dose (5 mg/kg) caused more rapid restoration of both the total power and fast as well as slow beta band power. These results suggest that GM1 has favorable effects on post-concussive neurophysiological symptoms in head injured animals.

Animals↗

PubMed1992

Central interaction of dexamethasone and RU-38486 on morphine antinociception in mice.

The central interference induced by dexamethasone and RU-38486, (a glucocorticoid receptor antagonist) on morphine antinociception were studied by using the tail flick test in mice. Dexamethasone, injected intracerebrally (i.c.v.) 10 minutes before morphine, dose-dependently reduced morphine antinociception, whereas RU-38486 which was injected with the same lag time, potentiated it. When dexamethasone and RU-38486 were administered together i.c.v., 10 minutes before morphine, an overall reduction of morphine antinociception was observed, similar to that observed with dexamethasone pretreatment only. The present results strongly suggest a central site of interaction for dexamethasone and RU-38486 on morphine antinociception; the short latency and the dose-related slope for this interaction may suggest a mechanism at least in part different from the glucocorticoid-induced genomic activation.

Animals↗

PubMed1992

Dexamethasone prevents epileptiform activity induced by morphine in in vivo and in vitro experiments.

The inhibitory effects exerted by dexamethasone on the epileptiform activity induced by morphine were investigated in two different experimental models with two different animal species. In the first series of experiments, dexamethasone administered i.v. in rabbits 30 min before i.c.v. administration of morphine completely prevented both epileptiform and background EEG as well as behavioral alterations induced by morphine. Cycloheximide (a protein synthesis inhibitor) pretreatment reversed the antagonistic effect induced by dexamethasone on the behavioral and EEG alterations induced by morphine. In the second series of experiments, the effects exerted by dexamethasone were investigated on morphine-induced CA1 epileptiform bursting on rat hippocampal slices in vitro. Dexamethasone pretreatment 10 to 60 min before morphine strongly prevented the morphine effects in a concentration- and time-dependent manner. Sixty min of dexamethasone pretreatment also prevented the epileptiform bursting induced by the selective mu opiate receptor agonist DAMGO, whereas it did not significantly affect the increase of the CA1 population spike amplitude due to the selective delta opiate receptor agonist DPDPE. The addition of cycloheximide to the slice-perfusing medium containing dexamethasone prevented the inhibitory effects of the drug toward the morphine and DAMGO-induced CA1 epileptiform bursting. Our results indicate that dexamethasone induces an inhibition on the epileptiform activity induced by morphine and DAMGO. The time lag (30-60 min) which is necessary for revealing the inhibitory influence of dexamethasone on opiate epileptiform activity induced both in vivo and in vitro, and the inhibitory effect exerted by cycloheximide on dexamethasone activity strongly support the hypothesis of a genomic corticosteroid effect within the central nervous system.

Animals↗

PubMed1992

Time- and dose-related influence of dexamethasone on morphine-induced hypermotility in mice.

The effect of interaction between dexamethasone (DEX) and morphine on locomotor activity in mice was investigated. DEX alone (1.0 and 10 mg/kg i.p.) did not affect the locomotor activity of mice when injected immediately before the beginning of the session. DEX (1.0 mg) injected two hours before the session did not modify the activity of mice whereas the higher dose (10 mg) increased it. Morphine alone (30 mg/kp i.p.) induced a consistent increase in the locomotor activity. DEX (1.0 mg) injected at the same time as morphine reduced the morphine hypermotility, whereas that injected two hours before morphine had no influence on morphine hypermotility. DEX (10 mg) consistently potentiated the morphine hypermotility both when administered together and two hours before morphine. We conclude that DEX exerts an important time- and dose-related influence on morphine-induced hyperactivity in mice.

Animals↗

PubMed1991

Dexamethasone induces biphasic effect on morphine hypermotility in mice: a dose-related phenomenon.

The present study examined interaction between dexamethasone (DEX) and morphine on the locomotor activity in groups of mice by using the activity cage test. Morphine administration (30-75-150 mg/kg, ip) induced a dose-related increase of the locomotor activity of mice, whereas DEX per se (0.1-1.0-10 mg/kg, ip) did not modify the activity of control mice. Pretreatment of mice with DEX 0.1 mg did not alter the hyperactivity produced by the three doses of morphine. In contrast, DEX administered at 1.0 mg reduced the morphine effects on locomotor activity, whereas DEX at 10 mg potentiated the morphine hypermotility. Our results suggest that DEX may play an important regulatory role on the central effects of morphine through a differential modulation of brain excitability systems.

Animals↗

PubMed1991

The interaction of peripherally and centrally administered dexamethasone and RU 38486 on morphine analgesia in mice.

1. Dexamethasone or RU 38486 were administered intraperitoneally or intracerebroventricularly to mice 10 or 120 min before morphine administration. The interaction of these drugs with the analgesic effects of morphine was examined using the hot plate test. 2. Dexamethasone i.p. pretreatment reduced analgesic responses to morphine injected 120 min but not 10 min after dexamethasone; i.c.v. injection of dexamethasone 10 and 120 min before morphine administration was effective in reducing morphine analgesia. 3. RU 38486 i.c.v. pretreatment (but not i.p. pretreatment) performed 120 (but not 10) min before morphine administration enhanced morphine analgesic effects. 4. These results, particularly the effects of drug interaction for i.c.v. administration, strongly confirm a central site for dexamethasone and RU 38486 action.

Analgesia↗

PubMed1991

Heroin induces changes in mother-infant monkey communication and subsequent disruption of their dyadic interaction.

Heroin was given in a single, low dose (0.2 mg/kg i.v.) to the mother monkey of mother-infant pairs, living in a stable community of 30 individuals (Macaca fascicularis; six pairs treated plus six controls, in experiments repeated twice). The drug did not induce alterations in the response of the mother to the infant's calling signals when they were placed in a new environment denoting a potentially dangerous situation. However, after being returned to the community cage, the treated mother rarely responded to the infant's calling (non-alarming, non-vocal) signals (P less than 0.02). This behaviour was followed by an increased latency of the infant-to-mother approach, by a diminution of the reciprocal ventroventral clasping as well as a diminution of the overall duration of clasping, and by an increase in nipple suckling (unusual for the age), as compared to saline-treated controls (P less than 0.05, P less than 0.02, P less than 0.025, and P less than 0.05, respectively). Analysis of behavioural sequences strongly confirmed this relationship among data (P less than 0.01 and P less than 0.025). Even short lasting, pharmacologically induced failure in the non-vocal communication of a mother monkey may in itself constitute a pathogenetic mechanism. This is an important cause of the disruption of her dyadic interaction with the infant which consequently upsets the infant's behaviour.

Animal Communication↗

PubMed1991

Long-term changes induced by developmental handling on pain threshold: effects of morphine and naloxone.

Mice pups were exposed daily to a stress-producing procedure (handling and saline injection) during the first 3 weeks of life. At 25 and 45 days of age, they were tested for differences in the tail-flick and hot-plate tests. The results indicate that chronic handling procedures during developmental stages can produce a long-lasting increase of the threshold for painful stimuli. This phenomenon is completely prevented by naloxone pretreatment and has enhancing effects on morphine analgesia, thus suggesting that postnatal handling can exert long-lasting interference on the sensitivity of some opioid receptor populations.

Animals↗

PubMed1990

Reproducibility of carcinogenic potencies estimated in different rodent species. Methylene chloride: a useful example.

The aim of this study was to investigate the reproducibility of carcinogenic potencies estimated by multistage model (and its linearized form) fitting to dose-response relationships referring to different rodent species and strains, different sexes, target organs and severity of prognosis. Methylene chloride represented a useful example since there were 11 single dose-response relationships available for the same administration route (inhalation) and for the above-mentioned variables. The multistage mathematical model and the 'linearized multistage' model (EPA's conservative procedure), which are the mainly adopted models for regulatory purposes, were used for the dose-response fitting of single trends and other different cumulative trends. The reproducibility of response frequencies at equal exposure doses was also analyzed. The mathematical function best describing each trend showed the constant presence of a linear component (for low doses) and, in the majority of cases, a quadratic second order component. Carcinogenic potencies were fairly consistent for the various parameters. A good interspecies reproducibility of carcinogenic potencies was observed. A high intraspecies reproducibility was also observed, even though obtained from different sexes, as well as varying degrees of severity of prognosis and, in the case of rats, different strains. The fluctuation of the estimated carcinogenic potencies was lower in mice than in rats.

Animals↗