Grazia Mengozzi

THE PLASMA KINETICS AND TISSUE DISTRIBUTION OF ENROFLOXACIN AND ITS METABOLITE CIPROFLOXACIN IN THE MUSCOVY DUCK

Intorre, L., Mengozzi, G., Bertini, S., Bagliacca, M., Luchetti, E. and Soldani, G., 1997. The plasma kinetics and tissue distribution of enrofloxacin and its metabolite ciprofloxacin in the Muscovy duck. Veterinary Research Communications, 21 (2), 127-136

AN ANALYSIS OF THE EFFECTS OF GALANIN ON GASTRIC-ACID SECRETION AND PLASMA-LEVELS OF GASTRIN IN THE DOG

The effects of galanin on gastric acid secretion and plasma levels of gastrin were studied in conscious dogs chronically fitted with gastric fistulas. Continuous i.v. infusion of galanin (2 micrograms.kg-1.h-1) for 2 h did not affect unstimulated total acid output or plasma levels of gastrin. In contrast, simultaneous i.v. infusion of galanin (1-2 micrograms.kg-1.h-1) inhibited the bombesin-stimulated output of acid whereas the effects of bombesin on gastrin output were not significantly modified. Galanin (2-4 micrograms.kg-1 i.v.) also depressed the secretory response to 2-deoxy-D-glucose without significantly affecting plasma gastrin levels. Galanin (2-4 micrograms.kg-1 i.v.) did not depress bethanechol-stimulated gastric acid output or inhibit histamine-stimulated gastric acid secretion. These findings indicate that glanin inhibits the bombesin- and 2-deoxy-D-glucose-stimulated secretion of gastric acid in conscious dogs by an action which is probably exerted at the level of the cholinergic nerve terminals.

HISTAMINE H3 RECEPTOR-MEDIATED INHIBITION OF GASTRIC-ACID SECRETION IN CONSCIOUS DOGS

SummaryThe effect of (R)α-methylhistamine (MH) and thioperamide (selective agonist and antagonist respectively of histamine H3 receptors) was examined in conscious gastric fistula dogs to investigate the role of histamine H3 receptors in the control of basal and stimulated gastric acid secretion. Intravenous infusion of MH at 0.3 and 0.6 μmol/kg/h caused a significant reduction of the 2-deoxy-d-glucose (2-DG)-stimulated acid output, maximal inhibition being 60%. The inhibitory effect of MH was counteracted by thioperamide (0.1 μmol/kg/h), which, by itself, did not modify the 2-DG-induced acid secretion. The increase in plasma gastrin levels induced by 2-DG was not significantly affected either by MH or by thioperamide. Under basal conditions MH (0.3 μmol/kg/h) did not induce any significant change in acid secretion and in plasma gastrin levels; by contrast, thioperamide (0.1 μmol/kg/h) produced a significant increase both in acid output and in plasma gastrin.These results suggest that activation of H3 receptors can exert a negative control in stimulated acid secretion in conscious dogs, when cholinergic pathways to acid secretion are activated by 2-DG; moreover, the slight, but significant, stimulatory effect of thioperamide on basal acid output and basal plasma gastrin may be suggestive for a tonic inhibitory role of H3 receptors in the regulation of basal acid secretion, however, a nonspecific effect of this drug cannot be excluded.

The effect of ethanol, beer, and wine on histamine release from the dog stomach

The mediator for the action of ethanol on the parietal cell of the stomach is not known. However, because the action of ethanol on gastric acid secretion was proposed to involve the release of histamine, we decided to investigate the effects of ethanol and some alcoholic beverages (red wine and beer) on histamine release from the dog stomach. After performing a splenectomy in anaesthetized beagle dogs, the gastrosplenic vein draining the corpus of the stomach was cannulated for blood withdrawal to evaluate the local release of gastrin and histamine by RIA. Intragastric administration of 200 ml of beer (4.8% ethanol) or red wine (12.5% ethanol) caused a significant enhancement in gastrin and histamine concentrations in venous blood from the stomach. By contrast, intragastric administration of pure ethanol in distilled water at the same concentrations of wine or beer did not significantly modify gastrin and histamine release. Integrated histamine responses for 20 min to beer and wine paralleled gastrin concentrations and were of the same magnitude of those induced by intravenous infusion of pentagastrin at 1 and 6 micrograms/ kg/h, respectively. We conclude that: 1) beer and red wine, but not pure ethanol, are potent releasers of histamine; 2) histamine release seems to be related to the gastrin response and probably occurs at the level of enterochromaffin-like (ECL) cells; 3) the ethanol content of these drinks is not important for their stimulant effect, indicating that some other components of beer and wine are responsible for gastrin and histamine release from the dog stomach.

Epidemiology of Intoxications in Italy

M. Amorena*1, F. Caloni2 and G. Mengozzi3 1Department of Food Science – Faculty of Veterinary Medicine – University of T eramo; 2Department of Veterinary Science and T echnologies for Food Safety – Faculty of Veterinary Medicine, University of Mila; 3Department of Veterinary Clinic, Faculty of Veterinary Medicine, University of Pisa, Italy *Correspondence: Department of Food Science, Faculty of Veterinary Medicine, University of T eramo, Piazza Aldo Moro ,64100, T eramo, Italy E-mail: amorena@unite.it

The role of peripheral opioid receptor subtypes in the modulation of gastric acid secretion and plasma gastrin in dogs

The peripheral opioid receptor subtypes involved in the regulation of gastric acid secretion were studied in dogs with both a gastric fistula and a Heidenhain pouch, by using the putative mu-opioid receptor agonist dermorphin, the delta-opioid receptor agonist [D-Ala2,D-Leu5]enkephalin (DADLE) and the kappa-opioid receptor agonist dynorphin-(1-13). Dermorphin caused a significant increase in basal acid secretion from both the gastric fistula and the Heidenhain pouch, while DADLE and dynorphin-(1-13) did not. Acid secretion stimulated by 2-deoxy-D-glucose from the gastric fistula was not modified by dermorphin and dynorphin-(1-13), while DADLE significantly inhibited it; at the same time gastric secretion from the Heidenhain pouch was significantly increased by dermorphin and unmodified by DADLE and dynorphin-(1-13). Dermorphin, DADLE or dynorphin-(1-13) did not modify plasma gastrin during basal or 2-deoxy-D-glucose-stimulated conditions. Submaximal bethanechol-stimulated secretion was increased by dermorphin and DADLE but unaffected by dynorphin-(1-13). Acid secretion from the gastric fistula stimulated by pentagastrin was enhanced by dermorphin, inhibited by DADLE and unaffected by dynorphin-(1-13). Dermorphin and DADLE significantly increased acid secretion from the Heidenhain pouch stimulated by pentagastrin, while dynorphin-(1-13) was ineffective. Naloxone prevented the stimulatory effects of dermorphin and DADLE on the Heidenhain pouch, but it reduced acid secretion from the gastric fistula further when given with DADLE. The inhibitory effects of DADLE on secretion from the gastric fistula were prevented by naltrindole, a selective antagonist of delta-opioid receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute intragastric application of capsaicin inhibits 2-deoxy-D-glucose : but not histamine-induced gastric acid secretion in the dog

In this study the influence of acute exposure of gastric mucosa to the sensory neurotoxin capsaicin on basal gastric acid secretion and on secretion induced by 2-deoxy-D-glucose or histamine in conscious dogs with gastric fistulae has been investigated. Under basal conditions intragastric capsaicin (160 microM, 50 ml of volume) did not induce any significant change in acid secretion and in plasma levels of gastrin. Total acid output induced by 2-deoxy-D-glucose (75 mg/kg i.v.) was significantly decreased by intragastric application of capsaicin, while plasma gastrin concentrations were unaffected. A direct stimulant of the parietal cells, such as histamine (64 micrograms/kg s.c.) increased gastric acid secretion which was not sensitive to capsaicin pretreatment. These findings indicate the involvement of capsaicin-sensitive fibers in the control of vagally-induced gastric acid secretion in the dog.

Inhibitory cholinergic effects of esaprazole on gastric-secretion and plasma gastrin-levels in the dog

The effects of esaprazole, a novel antiulcer drug, on gastric acid secretion and plasma gastrin levels were investigated in dogs provided with a gastric fistula or Heidenhain pouch. Esaprazole affected in a different extent the tests performed on dogs with a gastric fistula. The greatest inhibitory effect was obtained against 2-deoxy-D-glucose-induced acid output and gastrin release. An intermediate inhibition by esaprazole was detected on bethanechol-evoked secretion, and the lowest activity was found versus histamine-stimulated secretion. All these responses were strongly inhibited by the antimuscarinic drug pirenzepine used as reference drug. Moreover, both esaprazole and pirenzepine prevented the acid secretory response to a test meal in dogs with a Heidenhain pouch, without significantly affecting plasma gastrin levels. The present results suggest that the depressant action of esaprazole on gastric secretion depends on its peripheral anticholinergic activity, consisting of a partial blockade of acid output and a main reduction of vagally mediated gastrin release. On the basis of these findings, the antiulcer activity of esaprazole might be in part ascribed to its inhibitory effects on gastric secretion.

A comparative kinetic study of thiamphenicol in pre-ruminant lambs and calves

Eight healthy Holstein-Friesian calves and 8 Massese lambs of either sex (10-15-days old) were used to evaluate the pharmacokinetics of thiamphenicol after intravenous (i.v.) and oral (p.o.) administration (30 mg/kg). Plasma concentrations of thiamphenicol were determined by high-performance liquid chromatography on blood samples collected over 24h following treatment. Pharmacokinetic variables of the drug were calculated for both species and after both administration routes. After intravenous administration of thiamphenicol, a rapid distribution phase was followed by a slower elimination phase and, when thiamphenicol was administered p.o., the bioavailability was about 60% in both species. The higher volume of distribution and the longer biological elimination half-lives in pre-ruminant compared with adult animals indicate that thiamphenicol distributes widely into the extravascular compartment of pre-ruminants. Interspecies differences were observed in the kinetic behaviour of thiamphenicol with respect to peak plasma concentration (C(max)), time of peak plasma concentration (T(max)), elimination half-life (T(1/2)) and total clearance (Cl(B)). In conclusion intravenous or oral administration of 30 mg/kg of thiamphenicol provides plasma concentrations higher than minimum effective concentrations inhibiting bacterial growth (MICs) against most pathogens in pre-ruminant lambs and calves.

Characterization of in vivo plasma metabolites of tepoxalin in horses using LC―MS―MS

Tepoxalin is a veterinary drug registered for use in the dog as a dual inhibitor (cyclooxygenase-5 lipoxygenase). In the horse, it predominantly triggers a strong cyclooxygenase inhibition; this bias seems to be due to the action of its metabolite(s). Among these, only the RWJ-20142 is well known, while to the best of our knowledge no information is available on the other metabolites produced in vivo. Hence, the identification of its main metabolic pathway is pivotal to better understand its clinical activity. A suitable high performance liquid chromatography method has been applied to liquid chromatography-mass spectrometry for the characterization of the main metabolites in plasma of horses orally treated with tepoxalin. Mass spectrometry in full scan, product ion scan and precursor ion scan modes, provided information useful in elucidating large parts of the structure of the unknown metabolites detected. These structures are closely related to that of tepoxalin. One of these metabolites was speculated to be a structural isomer of the parental drug. These findings could be important to understand the pharmacology of tepoxalin in horses.