C. Beretta

In vitro febantel transformation by sheep and cattle ruminal fluids and metabolism by hepatic subcellular fractions from different animal species.

Febantel and one of its main metabolites, febantel sulphoxide, are chemically modified to only a slight extent when incubated in vitro with sheep and cattle ruminal fluids; other major metabolites, fenbendazole and oxfendazole, are respectively, oxidized to oxfendazole and reduced to fenbendazole. Febantel is negligibly metabolized by hepatic cytosol fractions but microsome preparations effect more extensive metabolic transformations. Important differences in this respect were found between microsome preparations from rat, horse, pig, cattle, sheep, chicken and trout livers.

Affinity of isoxsuprine for adrenoreceptors in equine digital artery and implications for vasodilatory action.

We used isolated equine digital arteries to study the vasodilatory mechanism of isoxsuprine, and fowl caecum preparations to investigate the affinity of the drug for beta-adrenoceptors. Isoxsuprine is a potent vasodilator of arterial smooth muscle that has been precontracted by an alpha-adrenoceptor agonist such as noradrenaline (log EC50 = -6.33 [-5.98; -6.68]). The present study indicates that its effect is due to alpha-adrenoceptor blockade since: (1) after a long lasting exposure to cumulative doses of isoxsuprine the vasoconstricting action of noradrenaline cannot be restored; (2) isoxsuprine does not promote relaxation on preparations precontracted by PGF2alpha; (3) isoxsuprine shifts the dose-response curve of noradrenaline to the right; and (4) its affinity (pK(B) = 6.90 [6.60; 7.20]) in this experiment is comparable to that in noradrenaline-precontracted preparations and is 14 times lower than that of the selective alpha1-adrenergic antagonist prazosin [pK(B) = 8.04 (7.40; 8.68]). The affinity of isoxsuprine for beta-adrenoceptors was 100 times lower than that of isoprenaline when tested on fowl caecum. This preparation has a large beta-adrenoceptor and negligible alpha-adrenoceptor population concerned with the control of smooth muscle motility. Our data suggest that the alpha-mediated effect of isoxsuprine on horse arterial smooth muscle is due to higher affinity of the drug for alpha- than beta-adrenoceptors rather than low concentration or functionality of beta-sites at this site. According to these data, pure beta2-agonists seem to be more profitable tools to determine vasodilation of the arterial bed in horses legs.

Comparative microsomal oxidation of febantel and its metabolite fenbendazole in various animal species

A comparison has been made of the in vitro metabolism of febantel (FBT) with that of one of its pharmacologically active metabolites fenbendazole (FBZ) using microsomal preparations from liver of sheep, calf, horse, pig, rat, chicken and trout. The oxidation of FBT to the corresponding sulphoxide appeared to be far more rapid with the exception of the trout, than a similar reaction with FBZ. Indeed FBT was further metabolized in several species by cyclization and further oxidation. This observation could have toxicological significance in view of the greater tetratogenic effects of the metabolite oxfendazole. Reaction rates were most rapid in pigs and sheep.

Some effects of caerulein on the motility of sheep forestomach and gall bladder

Summary Caerulein affects sheep forestomachs motility as well as that of gall bladder when intravenously administered, both through rapid injection and slow infusion. Such effects have been compared with those evoked by cholecystokinin in connection with those reported about pentagastrin.

Membrane lipid composition of subcellular fractions from lungs of rats treated with paraquat.

Summary Paraquat (125 mg/kg/os) affects body weight, ceruloplasmin plasma levels but not lungs weights of rats within a 192 h observation period. The analyses of cholesterol and fatty acid composition of the subcellular fractions from lungs of the treated rats reveal a significant, early and transient increase of cholesterol in mitochondrial membrane and marked, late reductions of palmitic, stearic, oleic and linoleic acids in cell debris and nuclei as well as in microsomal membranes. The results obtained indicate a probable weakening of the lipid structure of the membranes of these subcellular components.

Some effects of eledoisin on ruminant's reticular, omasal, ruminal and abomasal smooth muscles in vitro and in vivo

Abstract Eledoisin, which is an endecapeptide structurally related with Substance P, has been tested on ruminant forestomachal and abomasal smooth muscles both in vitro and in vivo . The peptide proved to be characterized by remarkable stimulant properties which occurred through a direct stimulation of these stru c tures. On account of these findings eledoisin or related peptides may be new therapeutic agents for the treatment of forestomachs atonia in ruminants.

The effects of caerulein on exocrine pancreatic secretion in pigs

Caerulein administered to anaesthetized pigs by slow i.v. infusions at doses of 0.5, 1.0 and 2.0 ng kg−1min−1 for 30 min, stimulated pancreatic juice production, increased the protein content of the juice and enhanced its amylolytic, lipolytic and proteolytic activities. In a single experiment, an i.v. infusion of secretin (0.001 U kg−1min−1) lasting through the whole experimental time, provoked potentiation of the caerulein stimulatory effects on pancreatic juice production, protein content and amylolytic activity.

Antimitochondrial activity of adriamycin and daunomycin on Saccharomyces cerevisiae.

Summary The authors have studied the antimitochondrial activity of Adriamycin and Daunomycin on Saccharomyces cerevisiae . It has been observed that: o a) Adriamycin and Danomycin selectively inhibit the growth of S. cerevisiae in non fermentable culture medium; b) the antibiotics induce a delay in the beginning of derepression of cytochrome synthesis, as demonstrated by the analysis of the growth curves of S. cerevisiae ; c) cells grown in presence of the drugs develop a reduced respiratory activity (39%–46% of control values); d) the respiratory rate of S. cerevisiae cells grown in absence of the antibiotics and harvested in stationary phase is not modified by adding directly Adriamycin and Daunomycin in the reaction tubes of the oxygen monitor; e) the analysis of cytochrome spectrum allows to assert that the antibiotics reduce the content of cytochrome a and a 3, coded and synthesized by mitochondria. The data abtained give evidence of a selective mitochondrial damage brought about by Adriamycin and Daunomycin an cells of S. cerevisiae .

Cholecystokinetic activity of caerulein in sheep(

Summary The cholecystokinetic properties of Caerulein in intact sheep show a good dose/effect relationship only when low doses of the peptide (1–10 ng/kg) are i.v. administered. At higher doses (100 ng/kg i.v.) the peptide show less activity. Pretreatment with reserpine or dibenamine strongly increases the cholecystokinetic effects of these doses and restores the dose/response relationship thus suggesting a catecholamine release produced by Caerulein when administered at high doses in sheep.

Effects of a crude preparation of colostrokinin compared with thoseof bradykinin on isolated rat duodenal segments

Summary A crude preparation of colostrokinin (CCOLK) obtained from pretreated bovine colostrum showed relaxing effects on isolated rat duodenal segments. These effects proved to be independent from catecholamine release and unrelated to true antispasmodic properties of the extract. Through various kinds of assays performed, CCOLK revealed some features resembling those of bradykinin and others which make the two substances clearly different. By changing the pH of the incubation media of the isolated preparations, CCOLK showed an interesting reversal of activity. The results obtained with a crude extract however should be further confirmed with pure colostrokinin or, better still, with a synthetic preparation of this peptide.