alberto loizzo - Academia.edu (original) (raw)

Papers by alberto loizzo

Inorganica Chimica Acta, 1983

Abstract The possible causes of dementia are many, and most cases are associated with degenerativ... more Abstract The possible causes of dementia are many, and most cases are associated with degenerative disease of the central nervous system; therefore, analysis of neurotransmitter systems may provide valuable information on the selectivity of the degenerative process. This report will deal with an experimental approach to dementia, through quantitative analysis of electroencephalographic (EEG) effects induced by aluminum on laboratory animals. In a first series of experiments we found that single oral doses of aluminum hydroxide induced in mice a dose-dependent diminution of the EEG power of 7.5 to 12 c/s frequency band, and a parallel dose-dependent increase of aluminum content in the brain, as early as 45 minutes after administration. It indicated that aluminum hydroxide is readily absorbed through an empty stomach or duodenum and is able to induced alterations of background EEG rhythms at doses equivalent to the ones used in human therapy. These and other data suggest that the EEG disturbances of background type, which are observed during the early stage in dialysis encephalopathy in man, may be due at least in part to a pharmacological and therefore reversible effect induced by an increased aluminum level in the brain. This effect was therefore investigated in a second series of experiments. Aluminum was found to induce, even in minute doses, profound effects on the hippocampal EEG of the rabbit after acute intracerebro-ventricular administration, consisting of long-lasting EEG desynchronization and, at higher doses, of EEG epileptiform pattern. These effects could be at least in part reversed or prevented by i.v. administration of drugs effective on the cholinergic and/or endorphinic systems. These results, although preliminary in nature, may contribute to the elucidation of the pathogenesis of experimental ‘dementia’ models in animals.

PubMed, 1993

The present study examined the effects of dexamethasone and RU-38486 on the spike-and-wave spindl... more 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.

Life Sciences, Jul 1, 1970

PubMed, Feb 1, 1996

The effect of dexamethasone on acute opiate withdrawal induced by mu, kappa and delta receptor ag... more The effect of dexamethasone on acute opiate withdrawal induced by mu, kappa and delta receptor agonists was investigated in vitro. After a 4-min in vitro exposure to morphine (less selective mu agonist), D-Ala2-N-methyl-Phe4-Gly5-ol)-enkephalin (DAGO; highly selective mu agonist) and trans(+/-)-3,4-dichloro-N-methyl-N-[2(1-pyrrolidynyl)cyclohexyl]- benzeneacetamide (U50-488H; highly selective kappa agonist) a strong contracture of guinea pig isolated ileum was observed after the addition of naloxone. This effect was also observed when rabbit isolated jejunum was pretreated with deltorphin (highly selective delta agonist). Dexamethasone treatment before or after the opioid agonists tested was capable of both preventing and reverting the naloxone-induced contracture after exposure to mu opiate agonists morphine and DAGO in a concentration- and time-dependent fashion. Also, the steroid reduced naloxone-induced contracture after the exposure to U50-488H only when injected before the kappa opiate agonist. Finally, it did not affect the naloxone contracture after exposure to deltorphin. Pretreatment with RU-38486, a glucocorticoid receptor antagonist, inhibited dexamethasone antagonism on responses to both mu and kappa agonists, whereas pretreatment with cycloheximide, a protein synthesis inhibitor, blocked only the antagonistic effects of dexamethasone on responses to the mu opioid agonists. Overall, these data indicate that dexamethasone induces significant effects on mu-mediated opiate with-drawal in vitro, which suggest an important functional interaction between corticosteroids and the opioid system primarily at the mu receptor level. The ability of RU-38486 and cycloheximide to block dexamethasone effects indicates that the steroid interference on mu-mediated withdrawal involves a protein synthesis-dependent mechanism via glucocorticoid receptor.

Peptides, Aug 1, 2010

Previously, we showed that our post-natal handling model induces pro-opiomelanocortin-derived (PO... more Previously, we showed that our post-natal handling model induces pro-opiomelanocortin-derived (POMC) endogenous systems alterations in male mice at weaning. These alterations last up to adult age, and are at the basis of adult hormonal and metabolic conditions similar to mild metabolic syndrome/type-2 diabetes. Here, we evaluate how sex influences post-natal programming in these metabolic conditions. Subjects are adult control (non-handled) female (NHF) and male (NHM) CD-1 mice; adult post-natal handled female (HF) and male (HM) mice. Handling consists of daily maternal separation (10 min) plus sham injection, from birth to weaning (21 days). In adult handled males (90-days old) we find not only POMC-derived hormones alterations (enhanced basal plasma corticosterone (+91%) and ACTH (+109%)) but also overweight (+5.4%), fasting hyperglycemia (+40%), hypertriglyceridemia (+21%), enhanced brain mRNA expression of hydroxysteroid(11-beta)dehydrogenase type-1 (HSD11B1) (+49%), and decreased mRNA-HSD11B2 (-39%). Conversely, uric acid, creatinine, HDL(C), total cholesterol, glucose and insulin incremental area under-the-curve are not affected. In females, post-natal handling does not produce both hormonal and dysmetabolic diabetes-like changes; but handling enhances n3- and n6-poly-unsaturated, and decreases saturated fatty acids content in erythrocyte membrane composition in HF versus NHF. In conclusion, for the first time we show that female sex in mice exerts effective protection against the hypothalamus-pituitary-adrenal homeostasis disruption induced by our post-natal handling model on POMC cleavage products; endocrine disruption is in turn responsible for altered metabolic programming in male mice. The role of sex hormones is still to be elucidated.

Plants used in traditional medicine represent a priceless tank of new bioactive molecules. Curren... more Plants used in traditional medicine represent a priceless tank of new bioactive molecules. Currently plant based drugs are researched and formulated in modern framework in new ways of medicine. Many of the thousands of plant species growing throughout the world have medicinal uses, containing active constituents having significative pharmacological actions. The root of the Tabernanthe iboga plant (also known as eboga) is the most frequently cited source of ibogaine, and this plant contains 11 other known psychoactive constituents. Ibogaine is the active chemical found in the African Tabernanthe iboga root as well as several other plant species. It is a strong, longlasting psychedelic used traditionally in a coming of age ritual but also known for its modern use in treating opiate addiction. Ibogaine has a long history of being used traditionally as a ceremonial, medicinal and spiritual tool in West Africa. Chemically, ibogaine is classified as a tryptamine, being a rigid analogue of melatonin, and is structurally similar to harmaline, another natural alkaloid and psychedelic agent. Ibogaine was first extracted from the Tabernanthe iboga root and it exerts primarily a stimulanting effect on the central nervous system. Ibogaine is a potent psychoactive substance showing also the unique property of significantly removing withdrawal symptoms and reducing cravings from substances causing chemical dependence. Recently, it has increasingly been used in western society as a unique therapy for detoxification from drugs and for other psychotherapeutic purposes. Given the above evidences, this is a comprehensive review of Tabernanthe iboga leading to contribute to the knowledge of the pharmacology, phytochemistry and therapeutic aspects of its psychoactive constituent, ibogaine.

Journal of Pharmacy and Pharmacology, May 1, 1995

The present study examines the influence of dexamethasone on the behavioural effects induced by b... more The present study examines the influence of dexamethasone on the behavioural effects induced by baclofen in mice. The behaviour elements considered were locomotor activity, motor co-ordination, catalepsy, stereotyped behaviour and antinociception. Baclofen (1·0–4·0–6·0 mg kg−1, i.p.) induced a significant reduction of all behavioural elements studied and an antinociceptive effect was recorded. Dexamethasone alone (0·1–0·5–1·0 mg kg−1, i.p.) did not induce significant changes in the behaviour elements considered. On the other hand, when the steroid was injected immediately before baclofen a significant reduction of baclofen's behavioural effects was found. Our results suggest a possible link between glucocorticoid and the GABA-ergic system.

Journal of Pharmacy and Pharmacology, Jun 1, 1996

Reduced clonidine anti-nociception in mice given low doses of dexamethasone has encouraged us to ... more Reduced clonidine anti-nociception in mice given low doses of dexamethasone has encouraged us to investigate the effects of dexamethasone pretreatment on locomotor hypoactivity, another example of clonidine-induced behaviour in mice. Dexamethasone administered intraperitoneally (0.1, 1 .O, 10 mg kg-I) 30 min before clonidine reduced clonidine-induced locomotor hypoactivity in the activity cage to an extent which was dose-dependent. Dexamethasone administered centrally (1 0 ng/mouse) 30 min before clonidine was also ablg to reduce clonidine-induced locomotor hypoactivity. Cycloheximide administered at a dose of 10 mg kg-2 h before clonidine did not change the effects of clonidine but was able to prevent the effects of dexamethasone on clonidine-induced hypoactivity. The glucocorticoid receptor antagonist RU38486 administered centrally at the dose of 1 ng/mouse did not change the effects of clonidine, whereas it was able to block the effects of dexamethasone on clonidine-induced locomotor hypoactivity. These results suggest that the effects of dexamethasone on clonidine-induced locomotor hypoactivity depend on the stimulating effects that dexamethasone exerts on the protein synthesis via the glucocorticoid receptor in the brain.

European Journal of Pharmacology, Jul 1, 1990

However, the administration brain met~~epha~n levels of either caffeine or theopbylline in the da... more However, the administration brain met~~epha~n levels of either caffeine or theopbylline in the dark phase resulted in a significant decrease in (48% and 41.28% decrease respectively). These results clearly indicate that methylxanthines affect the levels of the endogenous opioids: &endorphin and met-enkephalin and that these effects are diurnally controlled. In addition, the alterations in the levels of brain endogenous opioids observed following caffeine administration may in part explain the reported caffeine potentiation of morphine analgesia.

Pharmacological Research, May 1, 1992

Pharmaceuticals, policy and law, 2009

The European Medicines Agency has expressed 50 positive opinions recommending the granting of a m... more The European Medicines Agency has expressed 50 positive opinions recommending the granting of a marketing authorisation for an orphan medicinal product since the Regulation on orphan medicinal products (OMPs) entered into force in 2000. However, OMPs authorised at EU level are not always available at Member States (MS) level. We developed and distributed a questionnaire to collect information on the availability of 20 OMPs authorised before October 2006. The questionnaire included questions on the date of national market availability; the possibility of pre-marketing access programme; the distribution channel, the availability of a reimbursement policy. Twelve MS provided information: Austria, Belgium, Czech Republic, Denmark, Estonia, Finland, Hungary, Ireland, Italy, Latvia, Slovakia and UK. Results demonstrate that the availability of OMPs varies greatly among the 12 MS considered and market availability delays are highly variable. OMPs are often expensive drugs and the different MS reimbursement policies are hindering access to OMPs. Data show that since 2000 the number of OMPs has increased however issues including costs and reimbursement policies at MS level represent major barriers to real OMPs accessibility. This is a critical situation that deserves attention because of the evident inequalities that do exist with regards to OMPs accessibility among MS.

European Neuropsychopharmacology, 2001

XXXIII Congresso Nazionale della Società Italiana di Farmacologia . 7, 2007

Current neurobiology, 2013

This experiment was designed to study mechanisms of ‘phosphene vision’. In human physiology ‘phos... more This experiment was designed to study mechanisms of ‘phosphene vision’. In human physiology ‘phosphenes’ refer to luminous sensations produced by stimuli other than light. Experiments performed to reproduce the phenomenon, refer to phosphenes induced by electrical stimulation of retina and by accelerated particles during space flights. In order to study these mechanisms we programmed a series of experiments: in a preliminary experiment, visual evoked responses (VEPs), electroretinograms (ERGs) and oscillatory potentials (OPs) to flash stimulations were recorded in unanaesthetized and anaesthetized mice bearing chronically implanted electrodes. In the unanaesthetized animals, the responses displayed stimulus-depended increase in amplitude and decrease in latency, up to a plateau at about 2.082-2.383 phy. In particular, OPs at 1 Hz stimulus showed a maximal amplitude effect starting at about 2.684 phy intensity. In the anaesthetized animals, urethane produced a latency increase and an...

Current neurobiology, 2013

Visual evoked potentials (VEPs) and rapid oscillatory potentials (OPs) of male and female D BA/2 ... more Visual evoked potentials (VEPs) and rapid oscillatory potentials (OPs) of male and female D BA/2 mice were studied. Gender confrontations of the OPs spectral content and effects induced by a single low dose of physostigmine (0.05 mg/kg) were also evaluated. VEPs and OPs responses to luminous stimuli in male mice had a consistently lower latency than in females, but no gender differences in OPs spectral content (60-300 Hz) were evidenced. Physostigmine induced a further significant decrease in latency of evoked responses only in male mice and a significant decrease of amplitude in females. Spectral information contained in rapid OPs was not affected. Gender differences did not appear to be dependent barely on hormonal conditions, but on a more complex structural background.

Inorganica Chimica Acta, 1983

Abstract The possible causes of dementia are many, and most cases are associated with degenerativ... more Abstract The possible causes of dementia are many, and most cases are associated with degenerative disease of the central nervous system; therefore, analysis of neurotransmitter systems may provide valuable information on the selectivity of the degenerative process. This report will deal with an experimental approach to dementia, through quantitative analysis of electroencephalographic (EEG) effects induced by aluminum on laboratory animals. In a first series of experiments we found that single oral doses of aluminum hydroxide induced in mice a dose-dependent diminution of the EEG power of 7.5 to 12 c/s frequency band, and a parallel dose-dependent increase of aluminum content in the brain, as early as 45 minutes after administration. It indicated that aluminum hydroxide is readily absorbed through an empty stomach or duodenum and is able to induced alterations of background EEG rhythms at doses equivalent to the ones used in human therapy. These and other data suggest that the EEG disturbances of background type, which are observed during the early stage in dialysis encephalopathy in man, may be due at least in part to a pharmacological and therefore reversible effect induced by an increased aluminum level in the brain. This effect was therefore investigated in a second series of experiments. Aluminum was found to induce, even in minute doses, profound effects on the hippocampal EEG of the rabbit after acute intracerebro-ventricular administration, consisting of long-lasting EEG desynchronization and, at higher doses, of EEG epileptiform pattern. These effects could be at least in part reversed or prevented by i.v. administration of drugs effective on the cholinergic and/or endorphinic systems. These results, although preliminary in nature, may contribute to the elucidation of the pathogenesis of experimental ‘dementia’ models in animals.

PubMed, 1993

The present study examined the effects of dexamethasone and RU-38486 on the spike-and-wave spindl... more 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.

Life Sciences, Jul 1, 1970

PubMed, Feb 1, 1996

The effect of dexamethasone on acute opiate withdrawal induced by mu, kappa and delta receptor ag... more The effect of dexamethasone on acute opiate withdrawal induced by mu, kappa and delta receptor agonists was investigated in vitro. After a 4-min in vitro exposure to morphine (less selective mu agonist), D-Ala2-N-methyl-Phe4-Gly5-ol)-enkephalin (DAGO; highly selective mu agonist) and trans(+/-)-3,4-dichloro-N-methyl-N-[2(1-pyrrolidynyl)cyclohexyl]- benzeneacetamide (U50-488H; highly selective kappa agonist) a strong contracture of guinea pig isolated ileum was observed after the addition of naloxone. This effect was also observed when rabbit isolated jejunum was pretreated with deltorphin (highly selective delta agonist). Dexamethasone treatment before or after the opioid agonists tested was capable of both preventing and reverting the naloxone-induced contracture after exposure to mu opiate agonists morphine and DAGO in a concentration- and time-dependent fashion. Also, the steroid reduced naloxone-induced contracture after the exposure to U50-488H only when injected before the kappa opiate agonist. Finally, it did not affect the naloxone contracture after exposure to deltorphin. Pretreatment with RU-38486, a glucocorticoid receptor antagonist, inhibited dexamethasone antagonism on responses to both mu and kappa agonists, whereas pretreatment with cycloheximide, a protein synthesis inhibitor, blocked only the antagonistic effects of dexamethasone on responses to the mu opioid agonists. Overall, these data indicate that dexamethasone induces significant effects on mu-mediated opiate with-drawal in vitro, which suggest an important functional interaction between corticosteroids and the opioid system primarily at the mu receptor level. The ability of RU-38486 and cycloheximide to block dexamethasone effects indicates that the steroid interference on mu-mediated withdrawal involves a protein synthesis-dependent mechanism via glucocorticoid receptor.

Peptides, Aug 1, 2010

Previously, we showed that our post-natal handling model induces pro-opiomelanocortin-derived (PO... more Previously, we showed that our post-natal handling model induces pro-opiomelanocortin-derived (POMC) endogenous systems alterations in male mice at weaning. These alterations last up to adult age, and are at the basis of adult hormonal and metabolic conditions similar to mild metabolic syndrome/type-2 diabetes. Here, we evaluate how sex influences post-natal programming in these metabolic conditions. Subjects are adult control (non-handled) female (NHF) and male (NHM) CD-1 mice; adult post-natal handled female (HF) and male (HM) mice. Handling consists of daily maternal separation (10 min) plus sham injection, from birth to weaning (21 days). In adult handled males (90-days old) we find not only POMC-derived hormones alterations (enhanced basal plasma corticosterone (+91%) and ACTH (+109%)) but also overweight (+5.4%), fasting hyperglycemia (+40%), hypertriglyceridemia (+21%), enhanced brain mRNA expression of hydroxysteroid(11-beta)dehydrogenase type-1 (HSD11B1) (+49%), and decreased mRNA-HSD11B2 (-39%). Conversely, uric acid, creatinine, HDL(C), total cholesterol, glucose and insulin incremental area under-the-curve are not affected. In females, post-natal handling does not produce both hormonal and dysmetabolic diabetes-like changes; but handling enhances n3- and n6-poly-unsaturated, and decreases saturated fatty acids content in erythrocyte membrane composition in HF versus NHF. In conclusion, for the first time we show that female sex in mice exerts effective protection against the hypothalamus-pituitary-adrenal homeostasis disruption induced by our post-natal handling model on POMC cleavage products; endocrine disruption is in turn responsible for altered metabolic programming in male mice. The role of sex hormones is still to be elucidated.

Plants used in traditional medicine represent a priceless tank of new bioactive molecules. Curren... more Plants used in traditional medicine represent a priceless tank of new bioactive molecules. Currently plant based drugs are researched and formulated in modern framework in new ways of medicine. Many of the thousands of plant species growing throughout the world have medicinal uses, containing active constituents having significative pharmacological actions. The root of the Tabernanthe iboga plant (also known as eboga) is the most frequently cited source of ibogaine, and this plant contains 11 other known psychoactive constituents. Ibogaine is the active chemical found in the African Tabernanthe iboga root as well as several other plant species. It is a strong, longlasting psychedelic used traditionally in a coming of age ritual but also known for its modern use in treating opiate addiction. Ibogaine has a long history of being used traditionally as a ceremonial, medicinal and spiritual tool in West Africa. Chemically, ibogaine is classified as a tryptamine, being a rigid analogue of melatonin, and is structurally similar to harmaline, another natural alkaloid and psychedelic agent. Ibogaine was first extracted from the Tabernanthe iboga root and it exerts primarily a stimulanting effect on the central nervous system. Ibogaine is a potent psychoactive substance showing also the unique property of significantly removing withdrawal symptoms and reducing cravings from substances causing chemical dependence. Recently, it has increasingly been used in western society as a unique therapy for detoxification from drugs and for other psychotherapeutic purposes. Given the above evidences, this is a comprehensive review of Tabernanthe iboga leading to contribute to the knowledge of the pharmacology, phytochemistry and therapeutic aspects of its psychoactive constituent, ibogaine.

Journal of Pharmacy and Pharmacology, May 1, 1995

The present study examines the influence of dexamethasone on the behavioural effects induced by b... more The present study examines the influence of dexamethasone on the behavioural effects induced by baclofen in mice. The behaviour elements considered were locomotor activity, motor co-ordination, catalepsy, stereotyped behaviour and antinociception. Baclofen (1·0–4·0–6·0 mg kg−1, i.p.) induced a significant reduction of all behavioural elements studied and an antinociceptive effect was recorded. Dexamethasone alone (0·1–0·5–1·0 mg kg−1, i.p.) did not induce significant changes in the behaviour elements considered. On the other hand, when the steroid was injected immediately before baclofen a significant reduction of baclofen's behavioural effects was found. Our results suggest a possible link between glucocorticoid and the GABA-ergic system.

Journal of Pharmacy and Pharmacology, Jun 1, 1996

Reduced clonidine anti-nociception in mice given low doses of dexamethasone has encouraged us to ... more Reduced clonidine anti-nociception in mice given low doses of dexamethasone has encouraged us to investigate the effects of dexamethasone pretreatment on locomotor hypoactivity, another example of clonidine-induced behaviour in mice. Dexamethasone administered intraperitoneally (0.1, 1 .O, 10 mg kg-I) 30 min before clonidine reduced clonidine-induced locomotor hypoactivity in the activity cage to an extent which was dose-dependent. Dexamethasone administered centrally (1 0 ng/mouse) 30 min before clonidine was also ablg to reduce clonidine-induced locomotor hypoactivity. Cycloheximide administered at a dose of 10 mg kg-2 h before clonidine did not change the effects of clonidine but was able to prevent the effects of dexamethasone on clonidine-induced hypoactivity. The glucocorticoid receptor antagonist RU38486 administered centrally at the dose of 1 ng/mouse did not change the effects of clonidine, whereas it was able to block the effects of dexamethasone on clonidine-induced locomotor hypoactivity. These results suggest that the effects of dexamethasone on clonidine-induced locomotor hypoactivity depend on the stimulating effects that dexamethasone exerts on the protein synthesis via the glucocorticoid receptor in the brain.

European Journal of Pharmacology, Jul 1, 1990

However, the administration brain met~~epha~n levels of either caffeine or theopbylline in the da... more However, the administration brain met~~epha~n levels of either caffeine or theopbylline in the dark phase resulted in a significant decrease in (48% and 41.28% decrease respectively). These results clearly indicate that methylxanthines affect the levels of the endogenous opioids: &endorphin and met-enkephalin and that these effects are diurnally controlled. In addition, the alterations in the levels of brain endogenous opioids observed following caffeine administration may in part explain the reported caffeine potentiation of morphine analgesia.

Pharmacological Research, May 1, 1992

Pharmaceuticals, policy and law, 2009

The European Medicines Agency has expressed 50 positive opinions recommending the granting of a m... more The European Medicines Agency has expressed 50 positive opinions recommending the granting of a marketing authorisation for an orphan medicinal product since the Regulation on orphan medicinal products (OMPs) entered into force in 2000. However, OMPs authorised at EU level are not always available at Member States (MS) level. We developed and distributed a questionnaire to collect information on the availability of 20 OMPs authorised before October 2006. The questionnaire included questions on the date of national market availability; the possibility of pre-marketing access programme; the distribution channel, the availability of a reimbursement policy. Twelve MS provided information: Austria, Belgium, Czech Republic, Denmark, Estonia, Finland, Hungary, Ireland, Italy, Latvia, Slovakia and UK. Results demonstrate that the availability of OMPs varies greatly among the 12 MS considered and market availability delays are highly variable. OMPs are often expensive drugs and the different MS reimbursement policies are hindering access to OMPs. Data show that since 2000 the number of OMPs has increased however issues including costs and reimbursement policies at MS level represent major barriers to real OMPs accessibility. This is a critical situation that deserves attention because of the evident inequalities that do exist with regards to OMPs accessibility among MS.

European Neuropsychopharmacology, 2001

XXXIII Congresso Nazionale della Società Italiana di Farmacologia . 7, 2007

Current neurobiology, 2013

This experiment was designed to study mechanisms of ‘phosphene vision’. In human physiology ‘phos... more This experiment was designed to study mechanisms of ‘phosphene vision’. In human physiology ‘phosphenes’ refer to luminous sensations produced by stimuli other than light. Experiments performed to reproduce the phenomenon, refer to phosphenes induced by electrical stimulation of retina and by accelerated particles during space flights. In order to study these mechanisms we programmed a series of experiments: in a preliminary experiment, visual evoked responses (VEPs), electroretinograms (ERGs) and oscillatory potentials (OPs) to flash stimulations were recorded in unanaesthetized and anaesthetized mice bearing chronically implanted electrodes. In the unanaesthetized animals, the responses displayed stimulus-depended increase in amplitude and decrease in latency, up to a plateau at about 2.082-2.383 phy. In particular, OPs at 1 Hz stimulus showed a maximal amplitude effect starting at about 2.684 phy intensity. In the anaesthetized animals, urethane produced a latency increase and an...

Current neurobiology, 2013

Visual evoked potentials (VEPs) and rapid oscillatory potentials (OPs) of male and female D BA/2 ... more Visual evoked potentials (VEPs) and rapid oscillatory potentials (OPs) of male and female D BA/2 mice were studied. Gender confrontations of the OPs spectral content and effects induced by a single low dose of physostigmine (0.05 mg/kg) were also evaluated. VEPs and OPs responses to luminous stimuli in male mice had a consistently lower latency than in females, but no gender differences in OPs spectral content (60-300 Hz) were evidenced. Physostigmine induced a further significant decrease in latency of evoked responses only in male mice and a significant decrease of amplitude in females. Spectral information contained in rapid OPs was not affected. Gender differences did not appear to be dependent barely on hormonal conditions, but on a more complex structural background.