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Biomedical subjects

Y Ruckebusch

Publications and source records attributed to Y Ruckebusch.

At least 91 records · Page 5Linked to original sources

Pharmacology of reticulo-ruminal motor function.

experimental studies of the pharmacological control of the reticulo-rumen reveal two major central inhibitory pathways: (i) an adrenergic system which inhibits the magnitude of reticulo-ruminal movements and involves alpha 2-receptors and (ii) an inhibitory opioid system, which modulates the rate of the contractions. In addition, the coarseness of the stomach contents and the masticatory movements represent the major excitatory inputs to the gastric centres, hence the hypomotility and stasis observed in disease processes which lead to anorexia. Finally, the amplitude of reticular contractions will tend to vary inversely with the rate of contractions following the administration of stimulatory drugs acting centrally. As a practical statement, a direct action on the gastric centres is possible for drugs such as alpha blockers and/or morphine antagonists. Reflex excitatory effects may be induced by stimulation of muscarinic receptors of the reticulorumen wall as long as it remains below the threshold of a neuromuscular blockade. The highly complex mechanisms whereby reticuloruminal movements are regulated provide for (i) drug interactions, like those of histamine antagonists and opioid agonists, (ii) reflex inhibition of both amplitude and frequency of contractions arising from an enhanced abomaso-duodenal motility, like that induced by serotonin, and (iii) reflex stimulation of the rate of contractions elicited by the i.v. injection of catecholamines, an effect limited to the sheep. The multifactorial nature of reticuloruminal function suggests that treatment is unlikely to effect a cure but should materially re-establish a more normal motility. Further studies, required in diseased animals to provide for a curative use of drugs and a more thorough understanding of drug effects in normal ruminants, represent only a first step toward rational therapy. In addition, the extrapolation of drug effects from sheep to calves or cattle could be hazardous, especially for drugs whose mechanisms of action are currently unknown.

Adrenergic Agonists↗

Selective blockade of the responses of reticulo-ruminal muscle to 5-HT in sheep.

The effects of intravenous administration of 5-HT on the patterns of reticulo-rumen contractions were studied in conscious sheep. Contractions were measured by strain gauges applied to the external wall of the reticulum and the ventral and/or dorsal sac of the rumen. The responses to 5-HT comprised (i) a short-lived contraction followed by (ii) a sustained increase in muscle tone and (iii) a concomitant inhibition of the extrinsic reticulo-rumen contractions. The corresponding blockades produced by (i) atropine, (ii) 5-HT antagonists and (iii) chemical sympathectomy suggest involvement of a peripheral cholinergic mechanism in the initial contractile response and a central adrenergic mechanism in the reflex inhibition of extrinsic reticulo-rumen contractions.

Animals↗

[Inhibitory role of the opioid system in the initiation of rumination in sheep].

Major movements of the reticulo-rumen occur approximately once per minute as a result of periodic vagal motor discharges from "gastric centres" located in the medulla oblongata. During rumination evoked by stroking the interior wall of the reticulum or caused by the injection (bolus) of catecholamines, an additional contraction of the reticulum occurs at the time of regurgitation before the normal biphasic contraction. In sheep, the intravenous (IV) and intracerebroventricular (ICV) administration of naloxone at the doses of 0.1 mg/kg and 10 micrograms/kg respectively, enhances the occurrence of rumination caused by adrenaline. Morphine has opposite effects. Rumination can also be induced by catecholamines in sheep under naloxone regardless of the coarseness of the diet and during eating. The results suggest the involvement of an inhibitory opioid system in the central regulation of rumination and then in the occurrence of reticular contractions linked to regurgitation.

Animals↗

Development of digestive functions in the newborn ruminant.

To assess the progress of developing digestive functions accurately, it is necessary to evaluate the relative changes of certain variables. Observations have been reported on anatomical, biochemical and physiological changes that occur during the digestive adaptation of the neonatal lamb or calf to the extra-uterine life. For example, chymosin, a milk-clotting acid protease, is maintained by the milk diet at a high level until weaning in calves, as a result of the stimulation by casein of the rate of chymosin synthesis.

Action Potentials↗

Pharmacokinetics of dexamethasone and its effect on adrenal gland function in the dog.

The pharmacokinetics of dexamethasone (DXM) was studied in a group of 5 dogs given DXM alcohol or DXM 21-isonicotinate (as a solution) IV or IM (1 mg/kg of body weight) and DXM 21-isonicotinate (as a suspension) IM (0.1 or 1 mg/kg). Plasma concentrations were determined, using a high-performance liquid chromatography method. After IV administration, the half time of elimination was similar (120 to 140 minutes) for both formulations. In addition, all other pharmacokinetic parameters were not significantly different, indicating that DXM 21-isonicotinate renders DXM almost totally available. After IM administration, absorption was rapid for both solutions with a peak plasma concentration at 30 to 40 minutes. Bioavailability was approximately 100% for DXM alcohol, but limited (40%) for DXM 21-isonicotinate. After IM administration of DXM 21-isonicotinate (as a suspension) at 2 dosage rates (0.1 or 1 mg/kg), DXM was not detected in the plasma, suggesting a long phase of absorption. Plasma hydrocortisone (cortisol) values were similar after IM and IV administrations of DXM alcohol and DXM 21-isonicotinate (as a solution); after a short increase lasting 15 minutes, plasma hydrocortisone values decreased and returned to base line after a delay of 24 to 48 hours. After IM administration of DXM 21-isonicotinate as a suspension, plasma hydrocortisone values decreased for up to 10 days after the low dosage rate (0.1 mg/kg) and 1 month after the higher dosage rate (1 mg/kg).

Adrenal Glands↗

Electromyographic evaluation of the spontaneous and drug-induced motility of the cervix in sheep.

Recordings of electrical activity of the cervix were obtained in cycling and ovariectomized ewes that were fitted with extracellular electrodes and strain gauge transducers. Spontaneous electrical and mechanical events occurred with a typical cyclic pattern. Methods of evaluation of drug action on the cervix are suggested with respect to the observed spontaneous cyclic activity of the organ.

Animals↗

Dexamethasone in cattle: pharmacokinetics and action on the adrenal gland.

The pharmacokinetics of Dexamethasone (DXM) was studied in four cows all of which received DXM alcohol and DXM 21 isonicotinate (as a solution) by the intravenous and intramuscular routes. Concentrations of DXM and cortisol were determined using high performance liquid chromatography. An additional study was made in a second group of four cows which received intramuscular DXM 21 isonicotinate suspension for the assessment of DXM suppression of adrenal gland function. This was determined by measurements of base-line and ACTH-stimulated cortisol concentrations, before and following DXM administration. Following intravenous administration, the disposition kinetics of both formulations were described by a two-compartment open model. The half-times of elimination were similar; 335 and 291 min, respectively, for DXM alcohol and DXM 21 isonicotinate. All other pharmacokinetic parameters were not statistically different indicating that DXM was almost totally available (from DXM 21 isonicotinate). Following intramuscular administration, no significant difference in parameters was observed between the two formulations. Peak plasma concentrations were reached at 3 to 4 h post injection and bioavailability was approximately 70%. DXM was not detected in the plasma after the intramuscular administration of the suspension. The mean control plasma cortisol concentration was 8.8 +/- 3.03 ng/ml. Following intravenous and intramuscular administrations of DXM alcohol and DXM 21 isonicotinate (solution), cortisol concentrations initially increased. However, at 120 min (intravenous) and 2-4 h (intramuscular), concentrations were negligible; 24-72 h and 48-96 h, respectively elapsed before concentrations returned control values. Following DXM 21 isonicotinate (suspension) there was no initial increase and concentrations had not returned to normal in all four cows until 52 days post administration. Similarly, ACTH-stimulated plasma cortisol concentrations decreased progressively and significantly post administration. At 52 days, response to ACTH was normal in all animals.

Adrenal Glands↗

Minute rhythm of electrical spike bursts of the small intestine in different species.

Electrical activity of propagating spike bursts recurring at minute intervals was recorded from the small intestine by chronically implanted electrodes in the rabbit, cat, dog, sheep, and pig. This "minute rhythm" has been recorded previously from the intact human small intestine. It occurs in the jejunum with a period duration of 0.5-2.0 min in all species examined. The minute rhythm was accompanied by pressure waves propagating over a short distance, and the activity was most prominent before the onset of phase III of the myoelectric complex. The minute rhythm was activated by the infusion of saline in the jejunum, and it may possibly reflect a normal mechanism for the transport of fluid content.

Animals↗

Spontaneous motility of the cervix in cyclic and ovariectomized ewes and changes induced by exogenous hormones.

Continuous recordings of the electrical and mechanical activities of the cervix were made. Two basic patterns of electrical signal, short spike bursts and long spike bursts, showed close mechanical relationships with the record of mechanical activity. Electrical activity was organized in myoelectrical complexes including the regular alternation of phases of irregular spiking activity and phases of regular spiking activity. The myoelectrical complexes of the cervix existed independently of the sexual status although the frequency of recurrence did vary. The highest frequency was recorded during the periovulatory period around oestrus when each complex was synchronized with a similar pattern recorded from the uterine horns. At the end of the periovulatory period, the irregular spiking activity decreased, the myoelectrical complex pattern of the cervix and uterine horns consisting mainly of regular spiking activity at a high frequency until metoestrus. During the luteal phase, only the cervix remained active, with myoelectrical complexes formed mainly by phases of regular spiking activity recurring at long intervals. This pattern was also recorded after ovariectomy in the absence of hormonal treatment.

Action Potentials↗

Effects of motilin, somatostatin, and pancreatic polypeptide on the migrating myoelectric complex in pig and dog.

Spiking activity of the gastrointestinal tract was recorded in 4 fasted pigs and 4 fasted dogs during the intravenous infusion at two rates, 5 (rate A) and 20 (rate B) ng . kg-1 . min-1 of 13-Nle-motilin, somatostatin, and bovine pancreatic polypeptide. Infusions continued for 2 h in pigs and for 5 h in dogs. 13-Nle-Motilin was unable to induce a migrating myoelectric complex or to modify its frequency in the pig at either rate of infusion. In contrast, the infusion of 13-Nle-motilin at rate B in the dog induced a migrating myoelectric complex but delayed the occurrence of the following migrating myoelectric complex. However, the mean duration (74 +/- 22 min) of the migrating myoelectric complex interval in the 5 h of infusion did not significantly change compared with the control period (92 +/- 8 min). At rate B, somatostatin inhibited the gastroduodenal spiking activity in the pig and disrupted the migrating myoelectric complex pattern, whereas this hormone at both rates of infusion increased the frequency of the migrating myoelectric complex by 69.3% and 17.2%, respectively, in the dog. The infusion of bovine pancreatic polypeptide increased the frequency of the migrating myoelectric complex significantly by 36.4% and 82% at rates A and B in the pig and by 148% at rate A in the dog. Bovine pancreatic polypeptide also inhibited spiking activity in the duodenum but not in the jejunum at rate B in the dog. These results suggest that pancreatic polypeptide, but not somatostatin, may have a regulatory function on the rhythmicity of the migrating myoelectric complex in the dog and pig and that motilin does not control the occurrence of duodenal migrating myoelectric complex in the pig.

Action Potentials↗

Assessment of alpha-2 adrenergic antagonists on the central nervous system using reticular contraction in sheep as a model.

In contrast to others species, the activity of ruminant forestomach (reticulum) is under the control of the central nervous system. Xylazine, a potent alpha-2 agonist, was shown to inhibit reticular activity. The potential usefulness of this physiological response to evaluate drugs acting on central adrenoreceptors was assessed. In conscious sheep, reticular activity was recorded either by electromyographic or manometric techniques. It was demonstrated that xylazine inhibited reticular contraction in a dose-dependent manner. This inhibition, which displayed limited intra- and intersubject variation, was related to a central action of xylazine because vagal stimulation was able to elicit reticular contraction. The so-called specific alpha-2 antagonists (tolazoline and yohimbine) or nonspecific (phentolamine) antagonists reduced xylazine inhibition. In contrast, the so-called alpha-1 antagonists (chlorpromazine, chlorprothixene, nicergoline, prazosin and thymoxamine) were without effect. Schild plots for the antagonists tolazoline and yohimbine in competition with xylazine were linear and had slopes that were not significantly different from unity, indicating competitive antagonism. These results suggest that reticular contractions, a discrete and periodic phenomenon of central origin easily recorded in conscious sheep, could be a useful physiological model to assess the effect of drugs on the adrenoreceptors of the central nervous system.

Adrenergic alpha-Antagonists↗

Adrenocortical function and plasma biochemical values in dogs after subconjunctival treatment with methylprednisolone acetate.

The effects of subconjunctivally administered methylprednisolone acetate on adrenocortical function and blood composition were studied in five dogs. Two 10 mg doses of methylprednisolone acetate were injected at an interval of 21 days. Plasma cortisol concentrations (COR), ACTH-stimulated cortisol concentrations and other blood components were determined regularly. The normal plasma COR (5.7 +/- 2.62 ng/ml) was one of the lowest reported in the literature for the dog, possibly because of the specificity of the high performance liquid chromatographic assay and the experimental environment. Plasma COR was depressed only after the first administration of methylprednisolone acetate. ACTH stimulated COR was significantly depressed nine and 20 days after the first and second subconjunctival injection respectively. Otherwise blood composition was unchanged.

Adrenal Cortex↗

The pharmacokinetics of xylazine hydrochloride: an interspecific study.

The pharmacokinetic disposition of xylazine hydrochloride is described after both intravenous and intramuscular injection of a single dose, in four domestic species: horse, cattle, sheep and dog, by an original high performance liquid chromatographic technique. Remarkably small interspecific differences are reported. After intravenous administration, systemic half-life (t1/2 beta) ranged between 22 min (sheep) and 50 min (horse) while the distribution phase is transient with half-life (t1/2 alpha) ranging from 1.2 min (cattle) to 5.9 min (horse). The peak level of drug concentration in the plasma is reached after 12-14 min in all the species studied following intramuscular administration. Xylazine bioavailability, as measured by the ratios of the areas under the intravenous and intramuscular plasma concentration versus time curves, ranged from 52% to 90% in dog, 17% to 73% in sheep and 40% to 48% in horse. The low dosage in cattle did not permit calculation. Kinetic data are correlated with clinical data and the origins of interspecific differences are discussed.

Animals↗

Initiation of the migrating myoelectric complex in dogs.

1. Contractile and spike activity in the conscious dog were recorded from strain gauge force transducers and electrodes chronically implanted on the antrum, duodenum and jejunum. The pattern of activity was related to the time elapsed after feeding a daily meal, both in intact dogs and in dogs with antro-jejunal or oesophago-duodenal anastomoses. 2. From 8 to 10 h after feeding, transient reductions of the continuous antral spiking activity were recorded while phases of regular spiking activity (RSA) and contractions developed on the proximal intestine. 3. About 18 h after feeding, the post-prandial antral activity became intermittent, each period of contractions being accompanied by the duodenal development of a RSA phase. 4. The RSA phases were still initiated on the duodenum after an antro-jejunal anastomosis and after gastrectomy. 5. It is concluded that phases of RSA of the migrating myoelectric complex are initiated in the proximal part of the small intestine rather than in the stomach. It is suggested that the RSA phase exerts an inhibitory effect on the antrum which may serve to reduce the flow of digesta through the pylorus when the ability of the duodenum to receive chyme is restricted.

Action Potentials↗