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M T Tebano

Publications and source records attributed to M T Tebano.

11 recordsLinked to original sources
PubMed2004

Permissive role of adenosine A2A receptors on metabotropic glutamate receptor 5 (mGluR5)-mediated effects in the striatum.

The metabotropic glutamate receptors 5 (mGlu5Rs) and the adenosine A2A receptors (A2ARs) have been reported to functionally interact in the striatum. The aim of the present work was to verify the hypothesis that the state of activation of A2A Rs could influence mGlu5R-mediated effects in the striatum. In electrophysiological experiments (extracellular recording in rat corticostriatal slices), the ability of the selective mGlu5R agonist CHPG to potentiate the reduction of the field potential amplitude induced by NMDA was prevented not only by the selective mGlu5R antagonist MPEP, but also by the selective A2AR antagonist ZM 241385. Analogously, the application of CHPG potentiated NMDA-induced toxicity (measured by LDH release) in cultured striatal neurons, an effect that was abolished by both MPEP and ZM 241385. Finally, the A2AR agonist CGS 21680 potentiated CHGP effects, an action that was reproduced and abolished, respectively, by forskolin (an activator of the cAMP/protein kinase A, PKA, pathway) and KT 5720 (a PKA inhibitor). The results indicate that A2ARs exert a permissive role on mGlu5R-induced effects in the striatum. Such an interaction may represent an additional target for the development of therapeutic strategies towards striatal disorders.

Adenosine↗
PubMed2003

Modulation of glutamate release and excitotoxicity by adenosine A2A receptors.

Because an increased glutamate outflow is thought to play a crucial role in triggering excitotoxic neuronal death, drugs able to regulate glutamate release could be effective for the management of neurodegenerative diseases. In this article, the authors discuss the hypothesis that adenosine A2A receptor antagonists (A2A antagonists) may belong to the aforementioned category. In rats bilaterally lesioned with the excitotoxin quinolinic acid (QA) in the striatum, the A2A antagonist SCH 58261 significantly reduced the motor, EEG, and neuropathologic changes induced by the lesion. Such effects of SCH 58261 occurred only at low doses and were paralleled by an inhibition of QA-stimulated glutamate release. The role played by A2A antagonists in the regulation of glutamate outflow was also confirmed by preliminary results obtained in the model of paired-pulse stimulation in corticostriatal slices. Conversely, based on data obtained in cultured striatal neurons, A2A antagonists appear unable to directly inhibit NMDA effects. In conclusion, A2A antagonists show clear neuroprotective effects in models of brain injury, although their actual therapeutic potential needs to be confirmed in a wider range of doses and in models of neurodegenerative diseases in which presynaptic and postsynaptic effects play different relative roles.

Adenosine A2 Receptor Antagonists↗
PubMed1999

Effects of cholinergic drugs on neocortical EEG and flash-visual evoked potentials in the mouse.

The effects of single intraperitoneal injection of two cholinesterase inhibitors, physostigmine (PHY; 0.01, 0.025, 0.05, 0. 1, 0.2 mg/kg) and heptylphysostigmine (HEP; 0.5, 2, 6 mg/kg) on electroencephalographic (EEG) activity and flash visual evoked potentials (f-VEP) in the occipital cortex were compared in DBA/2 mice. EEG spectral analysis of awake periods showed that PHY at all doses and HEP at 2 mg/kg induced an increase of power in the 4.25- to 7-Hz frequency band. Furthermore, PHY at the higher doses and HEP at all doses induced a decrease of power in the 7.25- to 12-Hz frequency band, while the lower doses of PHY (0.01, 0.025 mg/kg) produced an increase of this band. EEG effects elicited by the two drugs were similar, when doses displaying analogous biochemical effects (acetylcholinesterase inhibition) were used (i.e. 0.01 and 0. 025 mg/kg of PHY versus 0.5 and 2 mg/kg of HEP). PHY and HEP induced similar changes in f-VEPs. Amplitudes of early and late components (P1N1, N1P2, P4N4 and particularly N1P3) were enhanced, while amplitudes of middle components were depressed after all doses. The peak latency measures were generally delayed, even though, after the lower doses, a trend to a latency reduction was evident in late components. This finding might indicate a possible effect on stimulus speed diffusion by 'low therapeutic' doses, analogous to the ones used in men. Our data show that both drugs are effective in modifying EEG and f-VEP parameters connected with brain cholinergic function, although in a very narrow dose range.

Animals↗
PubMed1997

Glutamate metabotropic receptors modulate the expression of in vitro epileptiform activity in rat hippocampal slices.

The effects of the mixed class I and II mGLUR agonist (+) 1S,3R-trans-amino-cyclopentane-1,3-dicarboxylic acid (ACPD) and antagonists (+) alpha-methyl-4-carboxyphenylglycine (MCPG) and L-2-amino-3-phosphonopropionic acid (L-AP3) on the basal neuronal excitability and on the expression of in vitro epileptiform activity produced by the convulsant drugs picrotoxin and penicillin were investigated in rat hippocampal slices. The duration of the CA1 epileptiform bursting produced by 0.05 mM picrotoxin or 1 mM penicillin or 0.075 mM ACPD was significantly (p<0.05) and dose-dependently decreased by 0.3-0.5 mM MCPG or L-AP3, but not by 0.05 mM ACPD. The data demonstrate an involvement of class I and II mGLURs in the basal neuronal excitability and in the expression of in vitro epileptiform activity produced by some convulsants.

Animals↗
PubMed1996

Prescriptions for mesalazine and sulphasalazine: a prevalence estimate of patients treated for inflammatory bowel disease in Rome.

BACKGROUND: Sulphasalazine and 5-amino salicyclic acid drugs are specifically indicated for the treatment of inflammatory bowel disease. AIM: To use drug consumption by a given population as a marker to estimate the number of patients with inflammatory bowel disease. METHODS: Prescriptions for sulphasalazine and mesalazine were identified for the 133000 inhabitants of a local health unit in Rome. Other prescriptions received by the patients, who were users of sulphasalazine or mesalazine, were also studied. RESULTS: 99465 patients received at least one prescription for any drug in 1991. Three hundred and seventy-six patients were prescribed sulphasalazine and/or mesalazine, an average of 3.8 prescriptions per patient. These patients were exposed more frequently than the general population to other drugs often used in inflammatory bowel disease treatment, for example, corticosteroids, anti-diarrhoeal drugs and intestinal anti-infectives. We identified that 258 of 100000 inhabitants were prescribed either sulphasalazine or mesalazine; 127 of 100000 inhabitants received full-dose treatment for at least 30 days, and 42.8 of 100000 inhabitants received prescriptions of either drug, also associated with systemic corticosteroids. CONCLUSION: The consumption of drugs used specifically for inflammatory bowel disease may act as a marker for the prevalence of the condition in a community.

Aminosalicylic Acids↗
PubMed1995

Clinical pharmacokinetics of cumulative very high dose of cisplatin in chemotherapy resistant solid tumors.

Cisplatin was administered to seven patients with advanced cancer in divided doses of 40 mg/m2 body surface daily for 5 consecutive days. The pharmacokinetics of total Pt was studied on the days 1, 3 and 5 of infusion. The renal function was assessed through the parameters usually applied in the clinical practice (serum creatinine level, creatinine clearance, urinary volume). Pt pharmacokinetics and the renal function did not show modifications outside the normal range. However, on day 5 of treatment patients showed increased alpha-half life and AUC of plasma Pt, as well as decreased Pt total body clearance and Pt renal clearance, associated to a significant (although still within normal range) increase in serum creatinine and a decrease in urinary volume. Moreover, a correlation between Pt pharmacokinetics and renal parameters (measured as the difference between the values of days 1 and 5 of treatment) was also found: the increase in creatinine was directly related to a decrease in Pt renal clearance and inversely related to Pt peak level in urine, while the latter was inversely related to a reduction of Pt renal clearance. It was concluded that very high doses of cisplatin are well tolerated in patients, although some parameters might suggest early impairment of the renal function.

Aged↗
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↗
PubMed1988

EEG spectral analysis after minor head injury in man.

A quantitative EEG analysis was performed on the posterior lead of 18 patients with their eyes closed 3-10 days after minor head injury. There was a significant increase of the mean power of slow alpha (8-10 c/sec), a reduction of fast alpha (10.5-13.5 c/sec), with a shift of mean alpha frequency towards lower values, and a reduction of fast beta (20.5-36 c/sec) in the patients with head injuries compared with the age- and sex-matched patients in the control group. Therefore, power spectral EEG analysis performed with the above-mentioned criteria may be suggested as a sensitive tool to be added to others during the neurophysiological follow-up studies of people with head injuries.

Accidents, Traffic↗
PubMed1987

Raised plasma concentrations of platelet factor 4 (PF4) in Crohn's disease.

Plasma platelet factor 4 (PF4), secreted by the platelets, is an index of platelet aggregation and thromboembolic risk. The authors assessed PF4 in 20 patients with Crohn's disease (ileitis in 13 patients, ileocolitis in seven) and in 20 healthy volunteers. Disease activity was low (Crohn's Disease Activity Index less than 150) in 11 patients and high in nine. Radioimmunoassay of PF4 using Abbott's Kit was performed on one sample of plasma from each subject (nv less than or equal to 0.324 nmol/ml), (nv less than or equal to 10 ng/ml). A significantly higher concentration of PF4 was found in Crohn's disease patients: 4.625 +/- 1.1 nmol/ml (142.5 +/- 36 ng/ml) than in the control group: 0.189 +/- 0.07 nmol/ml (5.6 +/- 4.8 ng/ml) (Z = 5.396, p less than 0.0001). No correlation was present between PF4 levels and activity, the site of disease, or medical treatment with or without prednisone.

Adult↗
PubMed1983

Blood coagulation alterations and thromboembolism in Crohn's disease.

The present study was undertaken in view of the higher incidence of thromboembolism in patients with Crohn's disease. The blood coagulation system was studied in 12 patients previously operated for Crohn's disease (8 cases of ileitis, 4 cases of colitis) and followed as out-patients. In 75% of cases, the disease was in an inactive stage. Eight patients showed slight lipid malabsorption. Serum levels of fibrinogen, platelets and factor V were shown to be significantly increased (p less than 0.001) as compared to controls. Prothrombin time and factors II, VII and X were shown to be decreased, while factors VIII and IX and antithrombin III were not significantly altered. Thrombocytosis and hyperfibrinogenemia, as reported in literature, seem to determine a condition of blood hypercoagulability, playing therefore a primary pathogenetic role in the genesis of thromboembolism in patients with Crohn's disease.

Blood Coagulation↗