Effects of prostaglandins on the peristaltic reflex of the guinea-pig ileum.
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Biomedical subjects
Publications and source records attributed to J Fontaine.
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Six sexual steroidal hormones (progesterone, pregnenolone, testosterone, ethinyl-oestradiol, oestriol and oestrone) inhibit acetylcholine- and histamine-induced contractions of the isolated guinea-pig ileum. Different degrees of inhibitory capacity were found. High concentrations of PGE1 and F2alpha reverse some of these inhibitions. This reversal seems to be non-specific and probably related to sensitization of the ileal smooth muscle by prostaglandins. The inhibitory action of sexual steroids might be non-specific as well. But a "corticoid-like" effect cannot be excluded.
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At the optimal concentration of 10 mg/l, vinblastine increases the submaximal contractions of the isolated guinea-pig ileum induced by the following agonists: acetylcholine, histamine, nicotine, angiotensine, prostaglandins E1 and F2alpha (but not serotonine). It also increases the contractions induced by transmural electrical stimulations of the guinea-pig ileum and reverses the inhibitory effect of non-steroidal anti-inflammatory drugs on these electrically-induced contractions.
Two methods of evaluating the activity of the foot-and-mouth disease vaccine are compared, leading to the evaluation of the number of protective doses 50% or potency. These methods differ in sensitivity, precision and equivalence potency-percentage of protection. For the same vaccine the value of the PD50 is always larger than that of Pb. We chose the Pb method using a diluent containing no adjuvant. Standards based on the evaluation of average potency have not been taken into consideration; only those standards based on the evaluation of minimum potency ensure respect of OIE's recommendation. This recommendation: 70% minimum potency with 0.95 probability is not an easier alternative, since the average protection observed corresponds in fact to at least 90% taking into account the biological variability of bovines.
Combined vaccines are used for many human and animal diseases. However, we have very few examples of combinations containing anti-foot-and-mouth valence which would allow easy immunization against differnet diseases without additional handling. Until now foot-and-mouth vaccination has been applied simultaneously with anti-brucellic vaccination (Baldoni, Renoux), andi-anthrax (Nobili) and vaccination against swine fever and Aujeszky's disease (Lysenko). During the last ten years we have particularly studied the association of anti-foot-and-mouth disease vaccines with anti-brucella and anti-rabies vaccines. We have shown the possiblity of combining these different antigens, either in classical aqueous vaccines in aluminum hydroxide, or in emulsified vaccines containing oily adjuvants. The anti-brucella valences may be agglutinogenic (H 38) or non-agglutinogenic (MacEwen 45/20). The combined vaccines "rabies + foot-and-mouth disease" and "brucellosis + foot-and-mouth disease" can be produced on an industrial scale. For many years millions of animals have been successfully vaccinated in France by means of a combined "rabies + foot-and-mouth disease" vaccine.
Medical and sanitary prevention of a growing number of major infectious diseases of bovines has led IFFA-Mérieux to investigate the association of vaccines and to define methods of utilization. Care has been taken to limit the number of interventions and at the same time to retain in the combined valences the efficacy they had when in a state of single constituent. The work which has been carried out for the last ten years, including the study of adjuvants as well as of incompatibility of associations, has permitted the improvement of formulas, reduced in volume (5 ml for a plurivalent dose), in aqueous excipient (aluminum hydroxide and saponin) or oily excipient (oil in water type). These formulas combine 3 foot-and-mouth disease valences with a rabies valence (fixed strain grown on cell culture) or with a brucellosis valence (strain B. abortus MacEwen 45/20 and B. melitensis H 38). The innocuity of these associations allows them to be used in sanitary compaigns; their efficacy is equal to that of monovalent vaccines. A logical vaccination calendar is proposed.
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The FIF technique applied to embryonic pancreas of the chick shows that the islte cells of the splenic lobe are able to take up L-DOPA and to synthesize high amounts of catecholamines from the 4th day of incubation. In the ventral pancreatic lobes fluorescent cells are not detectable before day 12. Later on, islet cells of the whole organ spontaneously accumulate fluorogenic amines and L-DOPA injection greatly increases the intensity of the fluorescence. It appears that in endocrine pancreas, as in various other polypeptide hormone producing cells, an aminoacid decarboxylase activity is detectable early in the differentiating process and precedes the amine storage. The possible role of fluorogenic monoamines in functional differentiation is discussed.
Twelve different non steroidal antiinflammatory drugs (NSAID), five steroidal antinflammatory drugs, morphine and chloroquine have been added at various concentrations to in vitro electrically-stimulated preparations of guinea-pig ileum. They all inhibit the electrically-induced contractions. Prostaglandins E as well as nicotine reverse this inhibition. These reversing effects are less evident on totally inhibiting drug concentrations than on partially inhibiting drug concentrations. It is suggested that this inhibiting effect could be due mostly to nervous as well as muscular membrane permeability changes induced by these drugs and not to inhibition of prostaglandin synthesis which could be only proposed as partial explanation for NSAID effects. The reversing action of nicotine could be related to a release of acetylcholine while a sensitization of guinea-pig ileum smooth muscle to acetylcholine could explain the reversing properties of prostaglandins.
Metoclopramide [(Mcp)-N-diethylaminoethyl-2-methoxy-4-amino-5-chloro-benzamide] was shown by the authors (This Journal 1973, 204, 239) to stimulate the isolated guinea-pig ileum, mainly by an indirecr cholinergic mechanism, to increase responses to acetylcholine (Ac) and transmural stimulation, and to inhibit responses to serotonin (5 HT) and histamine (H). Four structuraly related benzamide derivative (1211, 1265, 1308 and 1347) also stimutated the ileum, 1211 being the most active, and 1347 the least active, and resembled Mcp with regard to the responses to Ac, transmural stimulation and histamine. However, serotonin contractions were enhance by 1265 and 1347, while 1308 and 1211 were inhibitory. These observations suggest that a 4-amino group does not seem to be essential for the stimulant effect or the interference with Ac responses (1211, 1265, 1347), whereas a methylsulfonyl group (1347) and, to a lesser degree, a flour in 5 position (1265) sensitize the ileum towards 5 HT contractions.
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