Eur Rev Med Pharmacol Sci 2001 Jan-Feb;5(1):1-6
Department of Experimental and Clinical Pharmacology, University of Catania, School of Medicine, Italy.
Previous studies indicate that blood levels of cyclosporin-A are increased by concomittant administration of grapefruit juice in healthy subjects and patients. It was suggested that grapefruit juice could inhibit the metabolism of cyclosporin-A by CYP3A4, the predominant cytochrome P450 enzyme in the gut wall and liver. However, up to date, the mechanism of action of grapefruit juice has not been conclusively identified and no work has been conducted in animals to quantify its effect on cyclosporin-A metabolism. This study compared the disposition of cyclosporin-A (5 mg/kg) coadministered with grapefruit juice, orange juice or water (10 ml/kg) in male Sprague-Dawley rats. Time to peak concentration was about 5 h for each group. Area under the blood concentration-time curve and peak concentration of cyclosporin-A were increased by 31% and 20%, respectively, with grapefruit juice (P < 0.05). The effects of grapefruit juice were not duplicated by orange juice which did not differ significantly from water for any of the parameters tested. These results confirm that grapefruit juice may act as an inhibitor of drug metabolism altering the disposition of concomittantly administered cyclosporin-A in rats. Nonetheless, it was demonstrated that, under appropriate experimental conditions, rats may be suitable models for in vivo investigation of the interaction mechanism between grapefruit juice and cyclosporin-A.
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Altri formati: [Abstract + MeSH] [MEDLARS] Links: [102 articoli attinenti]
Peptides 1999;20(3):379-82
Institute of Pharmacology, University of Catania, School of Medicine, Italy.
Amylin (AMY) is a peptide of pancreatic origin principally involved in the carbohydrate metabolism, but that may interfere with central and peripheral dopamine (DA) pathways. The peptide, injected intracerebroventricularly (ICV) at the dose of 2.5 microg/rat, induced a decrease of copulatory activity in good copulators (GCO) and sluggish (SLU) male rats. The dose of 0.1 microg/rat did not affect significantly the sexual behavior of GCO rats, whereas AMY 0.5 microg/rat increased only the latency and reduced the frequency of ejaculation. At the dose of 2.5 microg/rat AMY antagonized the activation of sexual behavior induced by the DA receptor agonist, apomorphine administered subcutaneously (SC) at the dose of 100 microg/kg. Moreover, this inhibitory effect was blocked by the calcitonin gene-related peptide and AMY receptor antagonist, CGRP (8-37) fragment (injected ICV at the dose of 1 microg/rat). These data suggest that AMY may exert inhibitory effects on male sexual behavior in rats, probably interfering with central DA neurotransmission and with CGRP receptors.
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Altri formati: [Abstract + MeSH] [MEDLARS] Links: [113 articoli attinenti]
Eur J Pharmacol 1998 Oct 30;360(1):51-4
Institute of Pharmacology, University of Catania, School Medicine, Italy.
Adrenomedullin intracerebroventricularly administered (0.1 to 20 ng/rat i.c.v.), showed significant gastroprotective activity in a dose-dependent manner. When the peptide was intravenously administered (1 to 1000 ng/kg i.v.) it did not show significant gastroprotective activity in the same test. The gastroprotective effect of the peptide (10 ng/rat) was abolished by bilateral adrenalectomy, by pretreatment with the beta-adrenoceptor antagonist, propranolol (1 mg/kg i.p.), or by a calcitonin gene-related peptide (CGRP) receptor antagonist, CGRP-(8-37) fragment (1 or 10 ng/rat i.c.v.). This study showed that adrenomedullin is protective against reserpine-induced gastric lesions, that the action involves sympathetic nerve activity, and moreover interferes with CGRP receptors.
Traduci in ITALIANO! PMID: 9845272, UI: 99059405
Altri formati: [Abstract + MeSH] [MEDLARS] Links: [105 articoli attinenti] [Pharmacological Research]
Pharmacol Res 1998 Sep;38(3):221-4
Institute of Pharmacology, University of Catania School of Medicine, viale Andrea Doria 6, Catania, 95125, Italy.
Peripheral administration of amylin (40 microg kg-1) exerts gastroprotective effects in the reserpine-induced gastric lesions in the rat. This activity is decreased by pretreatment (30 min before) with (-)-sulpiride (0.1 mg kg-1 s.c.) or domperidone (0.1-2.5 mg kg-1 per os), dopamine DA2 antagonists. Pretreatment with SCH 23390 (0.5-4 mg kg-1 s.c.), a DA1 antagonist, at the maximal dose used, also significantly decreased the gastroprotective activity of the peptide. Amylin does not exert any gastroprotective effect in indomethacin-pretreated rats (7.5 mg kg-1 s.c., 30 min before), as well as in the aspirin-induced ulcer test (200 mg kg-1 per os at the time of amylin administration). Our data confirm that the gastroprotective effect of amylin in reserpine-induced gastric lesions involves, at least in part, the dopaminergic transmission, interfering with both the DA1 and DA2 receptor subtypes. Copyright 1998 The Italian Pharmacological Society
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Altri formati: [Abstract + MeSH] [MEDLARS] Links: [134 articoli attinenti]
Eur J Pharmacol 1997 Aug 6;332(2):209-13
Subcutaneous administration of amylin (20-40 micrograms/kg) prevented, in a dose-dependent manner, reserpine- and serotonin-induced gastric damage, but the anti-ulcer effect was not present when lesions were induced by pylorus ligation. The protective effect of amylin was inhibited by pretreatment with capsicin as well as CGRP-(8-37), a calcitonin gene-related peptide (CGRP) and amylin receptor antagonist, and was significantly reduced by domperidone, a dopamine D2 receptor antagonist, or neostigmine, an inhibitor of acetylcholinesterase. Our data suggest that the gastroprotective activity of amylin in some experimental models of gastric ulcers involves capsaicin-sensitive fibers and CGRP receptors. Moreover, the peptide interferes, at least in part, with the dopaminergic and parasympathetic systems.
Traduci in ITALIANO! PMID: 9286623, UI: 97432743
Life Sci 1997;60(11):PL175-80
Institute of Pharmacology, University of Catania School of Medicine, Italy.
Several peptide growth factors, including EGF, are known to protect endothelium from oxygen-related damage or ischemia-reperfusion, in vitro experiments show that such protective effect involves endogenous endothelium-related factors like nitric oxide and prostanoids. However, in vivo demonstrations of a possible role in related vascular diseases are lacking. In our experiments, human EGF and fraction C, a 3-10 kDa oligosaccharidic fraction from an aqueous extract of Triticum vulgare, known as growth promoters for several cell types including endothelial cells, were found protective against ischemic necrosis of the mouse tail induced by i.v. k-carrageenin plus endothelin-1. After i.p. injection, peak activities were observed at 10 micrograms/kg EGF and 2 mg/kg fraction C. Pretreatment with L-NAME reduced protection in a dose-dependent manner. Addition of indomethacin increased the effect of L-NAME, suggesting that both nitric oxide and eicosanoids are involved in the protective effect of EGF and fraction C.
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Altri formati: [Abstract + MeSH] [MEDLARS] Links: [165 articoli attinenti]
Experientia 1996 Jul 15;52(7):677-9
The effect of rat amylin on gastric emptying and intestinal transit in the rat was examined. Amylin administered intracerebroventricularly (1, 2, 2.5 or 4 micrograms/rat) produced the maximal decrease in gastric emptying and intestinal transit at the dose of 2.5 micrograms/rat. Higher doses produced a lower effect. Peripheral administration (25, 50 or 100 micrograms/kg) produced dose-dependent effects. Pre-treatment with neostigmine blocked the effect of amylin when it was centrally injected, while the effect of amylin given peripherally was partially reduced. Pre-treatment with domperidone decreased the inhibitory effect of peripherally injected amylin, but no effect was observed when the peptide was centrally injected.
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Altri formati: [Abstract + MeSH] [MEDLARS] Links: [122 articoli attinenti]
J Am Soc Nephrol 1996 May;7(5):786-91
Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
Although cyclosporine has become the mainstay of immunosuppression in organ transplantation, there is still no consensus on the criteria to optimize its anti-rejection activity with minimum toxicity. A clear and objective definition of target cyclosporine trough levels at different times from renal transplantation is still lacking, primarily because of the lack of a model correlating cyclosporine levels with probability of rejection or toxicity. In this study, logistic-regression model was developed that was applied to data collected retrospectively from two postoperative periods, i.e., Days 0 to 9 and 10 to 30, in 135 consecutive cadaveric renal transplant recipients, for a total of 1851 determinations. Only minimum and maximum trough levels were considered for each period. Concentration-response curves were estimated for Days 0 to 9 (P = 0.0001 for efficacy and P = 0.028 for toxicity) and for Days 10 to 30 (P = 0.015 for efficacy and P = 0.037 for toxicity). Therapeutic intervals of 330 to 430 ng/mL (parent compound in whole blood) for Days 0 to 9 and 260 to 390 ng/mL for Days 10 to 30 predicted an incidence of acute rejection of 22% and 12%, respectively, with a reasonably low toxicity that primarily consisted of elevation of serum aminotransferases.
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Altri formati: [Abstract + MeSH] [MEDLARS] Links: [259 articoli attinenti]
Funct Neurol 1995 Mar-Apr;10(2):83-90
Institute of Neuroscience, University of Catania School of Medicine, Italy.
Cognitive deficits are present in a substantial number of Multiple Sclerosis (MS) patients, particularly in those with the chronic-progressive type of the disorder. We assessed cognitive decline and its relationship with T2-weighted images on magnetic resonance imaging (MRI). We submitted a group of 26 patients with progressive MS to both MRI and a battery of neuropsychological tests. Cognitive impairment did not correlate with duration of illness or severity of neurological disability, but rather with the presence of extensive periventricular demyelination on MRI, evaluated as area of confluent lesions. These results suggest that cognitive deficits in MS represent a symptom of disease and not a parallel occurrence.
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Altri formati: [Abstract + MeSH] [MEDLARS] Links: [189 articoli attinenti]
Pharmacol Res 1995 Jan;31(1):67-72
Institute of Pharmacology, University of Catania Medical School, Italy.
Recent reports from our laboratory gave evidence showing that propionyl-L-carnitine (PLC), unlike L-carnitine (LC) and acetyl-L-carnitine (ALC), has anti-inflammatory activity in some models of vascular inflammation in rodents. The present paper shows that PLC (50 to 200 mg kg-1 i.p.) inhibits rat paw oedema induced by platelet activating factor (PAF), while LC and ALC, as well as indomethacin and phenylbutazone, are ineffective. The extent of the maximal inhibition produced by PLC at 200 mg kg-1 was comparable to that of betamethasone 0.05 mg kg-1 or sodium salicylate 100 mg kg-1. PLC inhibited also the early phase (1-2 h) of carrageenin-induced rat paw oedema, which is partly dependent on PAF release, but it was ineffective in the eicosanoid-dependent late phase (3-4 h) of the carrageenin oedema. We suggest that such anti-inflammatory activity of PLC may be due to various mechanisms converging on a stabilizing action upon biomembranes.
Traduci in ITALIANO! PMID: 7784308, UI: 95303758
Altri formati: [Abstract + MeSH] [MEDLARS] Links: [242 articoli attinenti]
Life Sci 1995;57(14):PL193-7
The anti-inflammatory activity of amylin was studied in different models of inflammation, and compared to that of CGRP. Both peptides were active against mouse ear oedema induced by croton oil and acetic acid-induced peritonitis in the rat. CGRP was more potent than amylin in both models. Pretreatment with CGRP 8-37 fragment blocked the anti-inflammatory activity of both peptides in croton oil ear oedema. No anti-inflammatory activity was evidenced against serotonin-induced rat paw oedema and plasma protein extravasation induced by dextran in rat skin. Our results suggest that amylin exerts anti-inflammatory activity only in inflammatory models characterized by a vascular component. This effect appears to be mediated by the involvement of CGRP receptors.
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Altri formati: [Abstract + MeSH] [MEDLARS] Links: [73 articoli attinenti]
Agents Actions 1994 Aug;42(1-2):29-33
Papaverine salicylate (MR-800) has been tested as a topical antiinflammatory agent in several models of skin inflammation in rodents, such as mouse ear dermatitis induced by croton oil, cantharidin or zymosan, and rat paw oedema induced by PAF. MR-800 exerted a dose-dependent inhibitory activity in all assays, when equimolar doses of sodium salicylate or papaverine were less effective, suggesting the existence of a favourable synergism between salicylate and papaverine.
Traduci in ITALIANO! PMID: 7847181, UI: 95149824
Altri formati: [Abstract + MeSH] [MEDLARS] Links: [248 articoli attinenti]
Brain Res 1994 May 9;645(1-2):13-8
Institute of Pharmacology, University of Catania, Italy.
Inhibition of forskolin-stimulated cAMP formation by (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) in rat hippocampal slices was partially obliterated by the adenosine-depleting enzyme, adenosine deaminase, or by the adenosine receptor agonist, 5'-(N-ethylcarboxamido)-adenosine, suggesting that activation of metabotropic glutamate receptors (mGluRs) modulates the release of endogenous adenosine. Consistent with this hypothesis, forskolin stimulated the release of purines from rat hippocampal slices, and this effect was reduced by 1S,3R-ACPD. To establish which transduction pathway is involved in the modulation of forskolin-stimulated purine release, we have tested the novel mGluR2 agonist, (2S,1'R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl)glycine (DCG-IV), which reduced forskolin-stimulated cAMP formation but, as opposed to 1S,3R-ACPD, did not stimulate polyphosphoinositide hydrolysis. DCG-IV was highly potent and more efficacious than 1S,3R-ACPD in inhibiting forskolin-stimulated purine release. Neither DCG-IV nor 1S,3R-ACPD reduced the release of purines stimulated by depolarizing concentrations of K+, suggesting that their effect was stimulus-specific. These results indicate that, in rat hippocampal slices, activation of mGluR2 receptors attenuates the release of purines induced by forskolin, a process that amplifies the final effect of forskolin on cAMP formation as a result of A2 purinergic receptor activation. Thus, the final effect of mGluR agonists on forskolin-stimulated cAMP formation in hippocampal slices depends on both a direct inhibition of adenylyl cyclase and the inhibition of adenosine release.
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Altri formati: [Abstract + MeSH] [MEDLARS] Links: [186 articoli attinenti]
Eur J Pharmacol 1994 Apr 21;256(2):R7-8
The anti-ulcer activity of calcitonin gene-related peptide (CGRP) was inhibited, in a dose-dependent manner, by pretreatment with NG-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthase. Our results suggest that endogenous nitric oxide is involved in the anti-ulcer activity of CGRP.
Traduci in ITALIANO! PMID: 8050460, UI: 94326793
Altri formati: [Abstract + MeSH] [MEDLARS] Links: [142 articoli attinenti]
Eur J Ophthalmol 1994 Apr-Jun;4(2):102-4
Lachrymal concentrations of the fluoroquinolone norfloxacin were studied in 30 subjects (aged 24-35 years) after a single ocular instillation (0.3% solution, 50 ul) in comparison with ofloxacin instilled at the same dose. Lachrymal levels were measured by high performance liquid chromatography (HPLC). Lachrymal peak levels were comparable 5 min after instillation but norfloxacin appeared to have a longer elimination half-life than ofloxacin. The AUC (area under the curve) for norfloxacin was therefore higher than for ofloxacin (35.9 and 10.7 mg* min/ml, respectively). These data suggest that norfloxacin may have higher corneal retention than ofloxacin, so this antibiotic may be indicated in superficial infections dependent on fluoroquinolone-sensitive bacteria.
Publication Types:
Traduci in ITALIANO! PMID: 7950332, UI: 95037665
Altri formati: [Abstract + MeSH] [MEDLARS] Links: [177 articoli attinenti]
Life Sci 1994;54(8):PL119-24
The anti-inflammatory activity of calcitonin gene-related peptide (CGRP) has been studied in cutaneous inflammation induced by croton oil (CO), arachidonic acid (AA), tetradecanoylphorbol acetate (TPA) or cantharidin (CA). Our results show that mouse ear inflammation induced by CO, AA or TPA is decreased by topical administration of CGRP, whereas that induced by CA is not affected. The dose-response and temporal analysis of CGRP effect show that the maximal activity is present at the dose of 30 pmol/ear and when administered 30 min after the irritating agent. Moreover, pretreatment with capsaicin is able to mimic the anti-inflammatory effect of exogenous CGRP, while simultaneous administration of CGRP and capsaicin produces a reduced response. Our results suggest that CGRP released from sensory.
Traduci in ITALIANO! PMID: 8107527, UI: 94150245
Altri formati: [Abstract + MeSH] [MEDLARS] Links: [213 articoli attinenti]
Drugs Exp Clin Res 1994;20(1):19-27
Intramuscular administration of medprotine, a protein fraction of human placenta (30-300 kDa), produced dose-dependent and long lasting analgesia as evaluated by various analgesic tests in mice. Activity was found in a dose range of 0.05-0.6 mg/kg in the phenylbenzoquinone and acetic acid writhing tests and 1.5-5 mg/kg in the hot-plate test. In this latter model, medprotine enhanced morphine-induced analgesia. Pretreatment with naloxone antagonized the effect of medprotine in all assays. The antinociceptive response of medprotine was not modified after a ten day pretreatment and no overt withdrawal symptom could be observed after either interruption of chronic treatment or administration of a precipitating dose of naloxone. It is concluded that the analgesic activity of medprotine may be mediated through either the opiate receptors or activation of endogenous opioidergic systems.
Traduci in ITALIANO! PMID: 7924891, UI: 95009412
Altri formati: [Abstract + MeSH] [MEDLARS] Links: [163 articoli attinenti]
J Physiol Paris 1993;87(6):389-92
Different classes of GABAergic drugs--baclofen, GABA, muscimol, Na-valproate, Mg-valproate and diazepam--were tested per os on ethanol-induced gastric lesions in rats. The GABAB agonist baclofen failed to affect gastric susceptibility to ethanol damage, while all the other compounds exerted a dose-dependent inhibition on haemorrhagic-necrotic lesions. This effect was not significantly reversed by the specific GABAA antagonist bicuculline, suggesting it to be independent from GABAA receptors. The blockade of prostaglandin synthesis by indomethacin significantly decreased the gastroprotective action of GABA, Na- and Mg-valproate, but did not antagonize the effect of muscimol and diazepam. Gastric juice volume and pH showed remarkable differences between the various treatments.
Traduci in ITALIANO! PMID: 8292990, UI: 94122697
Altri formati: [Abstract + MeSH] [MEDLARS] Links: [131 articoli attinenti]
Drugs Exp Clin Res 1993;19(5):213-7
The effects of propionyl-L-carnitine (PLC) in various models of inflammation were studied in rats and mice. PLC (50-200 mg/kg i.p.) dose-dependently inhibited the granuloma pouch induced by croton oil in rats, but failed to inhibit either cotton pellet granuloma or carrageenin-induced paw oedema and peritonitis. PLC (100 mg/kg i.p.) significantly reduced mouse ear oedema induced by croton oil, tetradecanoylphorbol acetate and arachidonic acid; in these models, PLC concomitantly reduced plasma extravasation, as evaluated by the leakage of Evans blue. In all the tested models, L-carnitine and acetyl-L-carnitine were ineffective, suggesting a specific protective role of PLC in the vascular component of the inflammatory process.
Traduci in ITALIANO! PMID: 8174493, UI: 94228965
Arzneimittelforschung 1992 Jan;42(1):25-7
Universita di Catania, Istituto di Chimica Biologica, Italy.
Comparative bioavailability of two formulations of diltiazem (Dilzene, CAS 42399-41-7), a calcium antagonist, was evaluated on 10 healthy volunteers (5 males and 5 females) in a cross-over study. A single dose of 120 mg of diltiazem was administered to the volunteers in the form of either two 60-mg tablets or a 120 mg controlled-release tablet. Plasma concentrations of diltiazem over a 24-h time interval were determined by HPLC analysis. Results of this investigation demonstrate that the controlled-release formulation of diltiazem has a lower Cmax value when compared to the 60 mg conventional tablet formulation, but a longer tmax and a superimposable AUC.
Traduci in ITALIANO! PMID: 1586376, UI: 92265038
Altri formati: [Abstract + MeSH] [MEDLARS] Links: [128 articoli attinenti]
Drugs Exp Clin Res 1992;18(11-12):481-5
In this study the pharmacological evaluation of MED-15, a non-acidic prodrug of tolmetin, is described. After oral administration the new compound shows a marked anti-inflammatory activity similar to that of tolmetin, but with minor ulcerogenic action and lower acute toxicity.
Traduci in ITALIANO! PMID: 1308474, UI: 93373817
Altri formati: [Abstract + MeSH] [MEDLARS] Links: [133 articoli attinenti]
Drugs Exp Clin Res 1992;18(11-12):465-7
The effects of sodium valproate (150 mg/kg) and carbamazepine (300 mg/kg), alone and in combination, on the content of glutathione (GSH) were investigated in the rat cerebral cortex. No modification was found either 4, 12 or 16 hours after treatment, suggesting that sodium valproate and carbamazepine do not affect the cortical GSH metabolism in rats.
Traduci in ITALIANO! PMID: 1308471, UI: 93373814
Altri formati: [Abstract + MeSH] [MEDLARS] Links: [116 articoli attinenti]
Recenti Prog Med 1988 May;79(5):220-3
Traduci in ITALIANO! PMID: 3175275, UI: 89018486
Altri formati: [Abstract + MeSH] [MEDLARS] Links: [222 articoli attinenti]
Int J Clin Pharmacol Res 1988;8(4):239-45
The pharmacokinetics of ofloxacin was studied in normal male volunteers selected from a student population. The aim of this study was to ascertain whether ofloxacin accumulated in plasma after administering six oral doses of the drug. The drug was administered in 300 mg tablets at intervals of 12 h for a total period of 72 h. The results clearly demonstrated that a modest accumulation of ofloxacin was observed between the first and second oral intake of the drug (R = 1.4); thereafter a steady-state plasma concentration was maintained at all time periods tested during the study. Furthermore, there was a broad fluctuation of approximately 80% between the Cmax and Cmin in the plasma levels of the drug during a 12-hour dosing interval. Hence demonstrating that a constant dose, repeatedly administered at a constant time interval of 12 h, ensured a broad range of concentrations of ofloxacin plasma, bile and other tissues which should favour the therapeutic success of the drug. There was agreement between the results of these studies and those in hospitalized patients suffering from severe infections. Analysis of ofloxacin after multiple dosing regimens in these patients showed measurable concentrations of the drug in the various tissues examined; hence suggesting a relative good bioavailability of the drug, which presumably reflected the high degree of success rates in these patients.
Traduci in ITALIANO! PMID: 3182113, UI: 89032703
Altri formati: [Abstract + MeSH] [MEDLARS] Links: [80 articoli attinenti]
Boll Soc Ital Biol Sper 1986 Nov 30;62(11):1357-63
Traduci in ITALIANO! PMID: 3828134, UI: 87157219