Flavio Moroni - Academia.edu (original) (raw)

Papers by Flavio Moroni

Pharmacological Research, Sep 1, 1992

Morphine and endorphins increased DA turnover and facilitated HVA accumulation in striatum. This ... more Morphine and endorphins increased DA turnover and facilitated HVA accumulation in striatum. This effect was maintained after lesion of the cortico-striatal or striato-nigral pathway. Morphine injected into substantia nigra (SN) did not change striatal DA metabolism but blocked the activation of TH by haloperidol. This action of morphine was not reversed by bicuculline. Since opiate receptors in SN are located on neurons connecting the SN with the forebrain (possibly on substance P neurons), these results suggest that intranigral morphine prevents the haloperidol-induced activation of striatal TH by interfering with a non-GABAergic (perhaps substance P) projection to SN.

Agents and actions, Dec 1, 1975

Murine neoplastic mast cells incubated with labelled histamine released14C-histamine when exposed... more Murine neoplastic mast cells incubated with labelled histamine released14C-histamine when exposed to increasing concentrations of noradrenaline.

Vision Research, Sep 1, 1993

The effects of ischemia-induced retinal damage were quantitatively evaluated in rats with the aim... more The effects of ischemia-induced retinal damage were quantitatively evaluated in rats with the aim of obtaining a suitable model to study the pathogenesis of the loss of retinal neurons after ischemic episodes. Anaesthetized rats were injected with 80 mg/kg i.v. of the fluorescein rose bengal dye and one eye was exposed to cold light for different periods (from 5 to 30 min). The animals were sacrificed at different times (1 and 4 hr; 2 and 7 days) after the lesion and the photochemically-induced damage was evaluated. The damaged retinae appeared thicker, numerous neurons of the inner nuclear layers showed swelling of the perinuclear cytoplasm and the retinal vessels were enlarged. The activity of choline acetyltransferase (ChAT) and glutamic acid decarboxylase (GAD), two marker enzymes of the GABAergic and cholinergic neurons, significantly decreased, indicating a degeneration of GABAergic and cholinergic amacrine cells.

PubMed, Dec 1, 1978

The injection of various doses of morphine, subcutaneously, or of beta-endorphin, intraventricula... more The injection of various doses of morphine, subcutaneously, or of beta-endorphin, intraventricularly, changes the turnover rate of gamma-aminobutyric acid (TRGABA) in the substantia nigra, globus pallidus and nucleus caudatus. The TRGABA decreases in N. caudatus but increases in globus pallidus and substantia nigra. These changes are dose related and can be inhibited by naltrexone. The increased TRGABA in globus pallidus elicited by these opioid receptor agonists may be associated with catalepsy since muscimol, a specific GABA receptor agonist, injected into the globus pallidus causes a dose-related catalepsy. Since this GABA receptor agonist injected into the substantia nigra fails to cause catalepsy, one can exclude that the increase in the TRGABA of substantia nigra elicited by opiate receptor agonists is operative in mediating the catalepsy elicited by opioids.

ChemInform, Aug 17, 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

The Society for Neuroscience Abstracts, Nov 11, 1994

Elsevier eBooks, 1979

ABSTRACT The interactions of beta endorphin with the cholinergic and the gabaergic systems in the... more ABSTRACT The interactions of beta endorphin with the cholinergic and the gabaergic systems in the rat C.N.S. were studied by massfragmentographically monitoring the turnover rate (TR) of GABA and Acetylcholine in stereomicroscopically isolated brain nuclei after administration of this opioid peptide. Intraventricular beta endorphin is able to induce analgesia and catalepsy as well as a dose-dependent decrease of the TRAch in the hippocampus and in the globus pallidus. No change has been observed in n. caudatus. Intraseptal injection of beta-endorphin selectively decrease the TRAch in the hippocampus without causing analgesia or catalepsy. This finding supports the idea that opiate receptors may control neuronal activities unrelated to analgesia and catalepsy. In the GABA field, intraventricular and intracaudatal injections of beta-endorphin decrease the TRGABA of the caudate and increase that of the globus pallidus. No effects were observed in the hippocampus. These modifications of the GABA metabolism in the basal nuclei are probably correlated with the extrapiramidal effects of beta-endorphin.

Nature, Dec 1, 1993

ty" among us servicemen and their families. A full reading of the report would show that the comm... more ty" among us servicemen and their families. A full reading of the report would show that the committee struggled with this idea throughout. Differences in exposure levels between the test types were explained in detail and an expert in risk communication was consulted in an attempt to reduce potential anxieties and fears. These efforts were balanced against the desire voiced by veterans to know what had happened to them and to end decades-long doubts about the causes of their health problems. The committee clearly states that not all the veterans' questions could be answered on the basis of rigorous scientific analysis. Yet, the veterans who have contacted the committee (now well over the 250 cited in the report) seem most grateful that their experience, so long ignored and denied, was finally affirmed. DavidP. Rail (Committee Chair

Molecular biology and structure functional anatomy and role in the CNS electrophysiology neuroche... more Molecular biology and structure functional anatomy and role in the CNS electrophysiology neurochemistry (releaser and signal transduction) pharmacology and drug design.

MedChemComm, 2011

Abstract Activation of poly (ADP-ribose) polymerase (PARP) is an important factor in controlling ... more Abstract Activation of poly (ADP-ribose) polymerase (PARP) is an important factor in controlling cell survival or death. As a consequence, therapeutic interventions with PARP-1 inhibitors are sought in different pathological conditions such as cancer, cardiovascular ...

Springer eBooks, Jan 10, 2008

Neuronal injury resulting from glutamate receptor-mediated excitotoxicity has been implicated in ... more Neuronal injury resulting from glutamate receptor-mediated excitotoxicity has been implicated in a wide spectrum of neurological disorders. Following dramatic results in the preclinical setting, anti-excitotoxic neuroprotective agents have been used in clinical trials for stroke and head injury, but the results have generally been unsuccessful. Hence, alternative targets in the excitotoxic cascade appear to be required. Poly(ADP-ribosyl)ation has been linked to the pathogenesis of numerous disorders of the CNS, including excitotoxicity and ischemic injury. A presumed cascade of glutamate receptor activation leading to excessive free radical formation, DNA damage and then overactivation of PARP-1 is based on studies with drugs that block these various steps. Along this classical view, experiments in our laboratory have shown that the intracellular depletion of ATP and NAD induced by PARP-1 overactivation leads to necrotic cell death in ischemic and excitotoxic models and that PARP-1 inhibitors are protective against necrotic but not apoptotic neuronal death. Therefore, it appears reasonable to propose PARP-1 inhibitors as useful therapeutic agents in pathological brain conditions where necrosis predominates.

Resuscitation, 1988

Benzodiazepine overdose is the most common of admission to the Toxicological Unit of the Universi... more Benzodiazepine overdose is the most common of admission to the Toxicological Unit of the University of Florence. The aim of this study has been to evaluate the efficiency of Ro 151799 in benzodiazepine and mixed drug overdoses. The administration of Ro 15-1788 was followed by a quick reversal of central nervous system depression and was more effective in benzodiazepine overdoses than in mixed drug overdoses. The dose was titrated individually and the range 2-10 mg was effective according to the conditions of the patient. In some cases, the comatose state relapsed; further administration of Ro 15-1788 again promptly reversed the condition. On awakening, two patients displayed anxiety and restlessness.

Frontiers in Pharmacology, 2019

Pulmonary fibrosis is the most frequent form of interstitial lung disease. Effective therapies ar... more Pulmonary fibrosis is the most frequent form of interstitial lung disease. Effective therapies are not yet available; novel therapeutic approaches are needed for counteracting fibrosis. Poly(ADP-ribose) polymerases are enzymes, involved in DNA repair and cell apoptosis. PARP-1 deficient mice exhibited reduced lung fibrosis in response to bleomycin treatment compared to wild-type controls. Histamine H 4 receptors (H 4 Rs) have been recognized as a new target for inflammatory and immune diseases, and H 4 R ligands reduced inflammation and oxidative stress in lung tissue. The aim of the study was to evaluate the cross-talk between PARP-1 and H 4 R in a model of bleomycin-induced lung fibrosis in PARP-1 −/− and WT mice. Animals were treated with bleomycin or saline by intra-tracheal injection. JNJ7777120, an H 4 R antagonist, or VUF8430, an H 4 R agonist, were administered i.p for 21 days. Airway resistance to inflation was evaluated, and lung tissues were processed for PARylated protein content, oxidative stress evaluation, and histology of small bronchi. The levels of pro-inflammatory (IL-1β and TNF-α), regulatory (IL-10), and pro-fibrotic (TGF-β) cytokines were evaluated. The deposition of αSMA was determined by immunofluorescence analysis. The results indicate that JNJ7777120 reduces PARylated protein production, decreases oxidative stress damage, and MPO, a marker for leukocyte tissue infiltration, in PARP-1 −/− mice. A significant decrease in the production of both IL-1β and TNF-α and a significant increase in IL-10 levels are observed in mice treated with H 4 R antagonist, suggesting a crucial anti-inflammatory activity of JNJ7777120. The smooth muscle layer thickness, the goblet cell relative number, and collagen deposition decreased following JNJ7777120 administration. The H 4 R antagonist treatment also reduces TGF-β production and αSMA deposition, suggesting an important role of JNJ7777120 in airway remodeling. Our results show that PARylation is essential for the pathogenesis of pulmonary fibrosis and propose that PARP-1 and H 4 Rs are both involved in inflammatory and fibrotic responses. JNJ7777120 treatment, in a condition of PARP-1 inhibition, exerts antiinflammatory and anti-fibrotic effects, reducing airway remodeling and bronchoconstriction. Therefore, selective inhibition of H 4 Rs together with non-toxic doses of selective PARP-1 inhibitors could have clinical relevance for the treatment of idiopathic pulmonary fibrosis.

Receptors As Supramolecular Entities, 1983

Publisher Summary This chapter discusses the effects of inhibitors of gamma-aminobutyric acid (GA... more Publisher Summary This chapter discusses the effects of inhibitors of gamma-aminobutyric acid (GABA) metabolism and transport on GABA output from the cerebral cortex. The activity of GABAergic neurons can be monitored in vivo by electrophysiological or biochemical techniques. Each technique has inherent advantages and limitations. The electrophysiological approach is usually very sensitive and offers the possibility of measuring rapid changes in the neuronal activity. However, the anatomical complexity of the brain and the lack of adequate histochemical controls make it difficult for the electrophysiologist to ascertain the nature of the neurotransmitter released by the activation of a particular neuron. Moreover, it is impossible to assess by electrophysiologica1 recording the global activity of the GABAergic neurons in a given brain area. The biochemical techniques usually provide information on the global function of a biochemically identified neuronal population. However, they are not sensitive enough to monitor the rapid changes in neuronal activity. The measurement of the release of neurotransmitters from nerve endings has always been considered the most direct approach to the study of neuronal activity as the release is, within certain limits, proportional to the impulse flow.