Gastrointestinal functional bowel disorders: new therapies.

Present therapies for functional gastrointestinal disorders are symptomatic and mainly treat altered bowel habits. New therapies are focused on nerve-gut communication dysfunction: 5-HT3 antagonists and 5-HT4 agonists have demonstrated activity in clinical trials. Promising targets for upper gut dysmotility drugs are motilin and cholecystokinin A receptors. Tachykinins, calcitonin gene-related peptide or glutamate antagonists are the most relevant candidates for visceral pain.

Acetorphan, an enkephalinase inhibitor, decreases gastric secretion in cats.

Acetorphan is an inhibitor of "enkephalinase" (EC 3.4.24.11) which has been shown to reduce in vivo and in vitro the degradation of enkephalins and other peptides. The effects of acetorphan on gastric secretion were studied in cats fitted with gastric fistulae and Heidenhain pouches. Acetorphan inhibited by 40-60% the acid secretion from the gastric fistulae after stimulation by submaximal doses of pentagastrin, histamine and 2 deoxy-D-glucose. These inhibitions were reduced or suppressed by naloxone. The meal-stimulated secretion from the fistulae was not changed after acetorphan. Acetorphan slightly and progressively reduced the pentagastrin-stimulated acid output from the Heidenhain pouches, and this effect was naloxone resistant. No change was found in the secretion from Heidenhain pouches under histamine stimulation, while meal-induced secretion of the pouches was increased by acetorphan, and this increase was not prevented by naloxone. Endogenous opioids probably exert an inhibitory regulatory control upon the gastric secretion of cats. In addition, non-opioid factors may be involved in the effect of acetorphan on meal-stimulated secretion.

Neuropeptide Y and sigma receptor agonists act through a common pathway to stimulate duodenal alkaline secretion in rats.

Neuropeptide Y (NPY) has been shown to mimic the effects of some sigma receptor agonists in the brain and to possess the same proabsorptive effect as these agonists in the isolated mouse jejunum. The aim of present study was to investigate the effect of NPY on duodenal alkaline secretion in the rat and to define its mode of action. NPY (0.01 to 3 micrograms/kg i.v.) induced a dose-related increase in duodenal bicarbonate secretion, the maximal effect being obtained at 1 micrograms/kg. This response was significantly inhibited by the i.v. administration of haloperidol, BMY 14802, devazepide, hexamethonium, tetrodotoxin and by bilateral truncal vagotomy, but not by SCH 23390, sulpiride, prazosin or atropine, whereas i.c.v. devazepide had no effect. This pharmacological profile is identical to that reported for sigma receptor agonists. The results suggest that NPY and sigma ligands act through a common pathway to stimulate duodenal alkaline secretion in the rat.

Central and peripheral effects of prostaglandin E2 and enprostil on exocrine pancreatic secretion in rats.

Prostaglandin E2 (PGE2) has been reported to exert some centrally mediated effects on intestinal motility and secretion and on gastric secretion, but it is not known whether such central effects exist on pancreatic secretion. The central and peripheral effects of PGE2 and enprostil, a long-acting, potent PGE2 analogue, were studied in conscious and anesthetized rats fitted with pancreatic fistulae. In chronically implanted, conscious rats, PGE2 inhibited the secretion of fluid, bicarbonate, and total protein in the pancreatic juice, both after i.v. or intracerebroventricular (icv) injections. The maximal inhibition was similar after both injection procedures (about 45% for fluid and bicarbonate and 60% for protein), but the potency of PGE2 was three to 10 times greater by the icv than the i.v. route. Enprostil also inhibited pancreatic secretion in a dose-related way. The maximal inhibition was larger than after PGE2 injection (about 70% for fluid and bicarbonate and 90% for protein). The potency of enprostil was five to 10 times lower by the icv than by the i.v. route. The diversion of gastric secretion suppressed the effect of icv PGE2 on fluid and bicarbonate output but not on protein and did not change the effect of enprostil on all the variables of pancreatic secretion. Adrenergic antagonists did not suppress the effect of icv PGE2 or enprostil on pancreatic secretion. In anesthetized rats, i.v. PGE2 inhibited hormone-stimulated protein secretion but did not change fluid and bicarbonate output, while i.v. enprostil inhibited cholecystokinin-stimulated fluid, bicarbonate, and protein output in the pancreatic juice.(ABSTRACT TRUNCATED AT 250 WORDS)

Central and peripheral effects of prostaglandin E2 and enprostil on gastric acid secretion in the rat.

The intracerebroventricular (i.c.v.) administration of prostaglandin E2 (PGE2) inhibits gastric secretion at doses that are inactive by i.v. administration in the rat. The present study was undertaken to examine the central and peripheral effects of enprostil, a potent synthetic PGE2 analogue, on gastric acid secretion as compared to those of PGE2. We used conscious rats equipped with a chronic gastric fistula and a cannula to allow injection into the third ventricle of the brain. Gastric acid output was measured under basal interdigestive conditions and during stimulation with submaximal doses of pentagastrin and histamine. Total inhibition of basal and stimulated gastric acid output was obtained after i.c.v. PGE2 and after i.c.v. or i.v. enprostil administration. After i.v. PGE2, the maximal observed inhibition was not greater than 50%. The ratio of ED50 values for i.v. administered to i.c.v. administered PGE2 was 64 or more, whereas the ratio of ED50 values for i.v. enprostil to i.c.v. enprostil was 9 to 13. Under all conditions studied, enprostil was more potent than PGE2 and this greater potency was more prominent after i.v. administration (ratio 250 to 2500) than after i.c.v. administration (ratio 10 to 400). The blockade of alpha 2-adrenoceptors by idazoxan did not suppress the inhibition of gastric secretion produced by i.c.v. PGE2 or enprostil. It is concluded that low doses of PGE2 inhibit gastric acid output mainly through a central mechanism, whereas low doses of enprostil potently inhibit gastric acid output through both a central and a peripheral mechanism. alpha 2-Adrenoceptors are not essential for the effect of i.c.v. prostanoids on gastric acid secretion.

Thiorphan and acetorphan inhibit gastric secretion by a central, non-opioid mechanism in the rat.

Thiorphan and its prodrug, acetorphan, are two inhibitors of enkephalinase (EC 3.4.24.11), a membrane-bound peptidase which plays an important role in the metabolic degradation of enkephalins. Since exogenous opioids have been reported to both stimulate and inhibit gastric secretion, the effects of thiorphan and acetorphan were studied in conscious rats equipped with chronic gastric fistulas. While i.v. thiorphan had no effect, both i.c.v. thiorphan and i.v. acetorphan potently inhibited the basal gastric acid output and the acid output stimulated by pentagastrin. Conversely, neither drug affected the histamine- or methacholine-induced stimulation of acid secretion. Neither thiorphan or acetorphan had any effect on the acid secretion stimulated by a combination of pentagastrin and acetylcholine in vagotomized rats. The results strongly suggest that both drugs inhibit gastric secretion through an effect at the level of the central nervous system, which decreases the vagal drive to the stomach. However, the effects of thiorphan and acetorphan were not prevented by naloxone. This is at variance with most of the effects of these drugs reported to date, including the inhibition of gastric secretion in cats. Furthermore, these effects were observed at doses which could inhibit other enzymes apart from enkephalinase. This suggests that the antisecretory action in rats is related to the protection of some non-opioid peptide(s) from degradation. In conclusion, both peptidase inhibitors inhibit gastric secretion of the rat through a central mechanism involving unknown, non-opioid peptide(s).

[Central inhibition of external pancreatic secretion by D-ala-2-metenkephalinamide in rats]. / Inhibition centrale de la sécrétion pancréatique externe par le D-ala-2-metenképhalinamide chez le rat.

Intracerebroventricular injections of D-Ala-2-Metenkephalinamide (D Alamide), a slowly metabolized Metenkephalin analogue, were made to conscious rats equipped with a chronic pancreatic fistula allowing the collection of pure pancreatic juice in its entirety. D Alamide induced a dose-related decrease in the volume of basal pancreatic secretion, as well as of bicarbonate and protein outputs. The effective doses of D Alamide were of the same order of magnitude as those necessary to induce analgesia or to decrease intestinal transit time in rats, as reported by others. The effect of D Alamide was totally blocked by naloxone, an opiate antagonist known to easily traverse the blood-brain barrier, while no blockade was found with naloxone methyl-bromide, an opiate antagonist which traverses the blood-brain barrier poorly and thus acts only peripherally. These results strongly suggest that the inhibition of pancreatic secretion induced by D Alamide is a central effect.

[Ocular lesions in lepromatous leprosy (author's transl)]. / Les lésions oculaires de la lèpre lépromateuse.

Ocular lesions observed in III cases of lepromatous or borderline leprosy are described. Tables are included which indicate the visual acuity, corneal sensitivity, and lesions noted in the appendages. Particular attention is paid to lesions in the pars plana, which include true posterior cyclitis having the appearance of "ants eggs" or "pearls" deposits on the retina, associated with vascular lesions and peripheral hyalitis. The absence of associated mucular edema is strongly emphasized. The etiopathogenicity of lesions of this type is probably directly related to leprous erythema nodosum. Detailed studies should be conducted on the chronological stages of these affections and their subsequent progression.

[An Ota's naevus in a West African child (author's transl)]. / Naevus de Ota chez un Africain de l'ouest.

Report of a case of Ota's naevus fuscocaeruleus ophtalmomaxillaris in an african child. The authors are not aware of a previous report of this deformity in Africa (South of the Sahara). They review the clinical and histological features of this naevus and describe in this case a pigmentary infiltration of corneal stroma.

[Mass treatment of onchocerciasis in 1996]. / Le traitement de masse de l'onchocercose en 1996.

Mass treatment of onchocerciasis has changed radically in the last 20 years. With implementation of the Onchocerciasis Control Programme (OCP), use of insecticides to control vector larvae has been effective but has not been extended to all infected areas due to the cost. The consequences of this problem have been lessened thanks to ivermectin, an effective drug that can be administered in a single yearly dose. Although ivermectin does not appear to induce major side-effects, surveillance is necessary after administration in polyparasitized subjects living in zones where loaiasis is present and in hypermicrofilaremic subjects. To assist in the fight against onchocerciasis, ivermectin is distributed free of charge through the Mectizan Foundation by Merck Laboratories. Inexpensive community distribution programs with active participation of the populations at risk have demonstrated their usefulness. The results of mass treatment through the Mectizan Foundation have been excellent. Non-governmental organizations and in particular the Organization for the Prevention of Blindness (OPB) have become increasingly involved in the fight against onchocerciasis. The campaign conducted by the OPB in Mali, Senegal and Guinea illustrate this involvement. The role of non-governmental organizations expanded greatly with the implementation of the APOC programme supported by the World Bank.

[Trachoma prevalence in the Sahel: report of a 1978 survey in Gourma area (Mali) (author's transl)]. / Réalité du trachome au Sahel. A propos d'une enquête dans la région du Gourma (Mali) 1978.

Report of a survey conducted in 1978 in the Niger sweep on a population consisting for one third of adults and for two thirds of children and adolescents. 2.571 persons have been controlled, giving evidence of 441 cases of trachoma (17,15 p. 100), 327 of which were evolutive and 114 cicatricial; 30,4 p. 100 of the cases were severe and 10 p. 100 suffered of a loss of visual acuity.

[Late aspects of palpebral anthrax (author's transl)]. / Le charbon palpébral en fin d'évolution.

Report of 5 cases of palpebral anthrax treated after the acute phase, in a cicatricial or precicatricial stade. The authors recommend to delay plastic surgery up to three months and to select total skin graft for upper eye-lid and pediculed skin flap for lower eye-lid.

[Corneal sensibility in 57 black Africans. A study based on 113 biomicroscopically normal ocular globes (author's transl)]. / Etude de la sensibilité cornéenne chez 57 Africains de race noire. A propos de 113 globes biomicroscopiquement sains.

This study of the corneal sensitivity in 57 sahelian black Africans with a biomicroscopically normal cornea demonstrated that most of them (80,8 p. 100) had a normal corneal esthesia. The others (19,2 p. 100) having an hypoesthesia are older than the average age of this group and have a lower sociocultural status.

[Orbital and ocular tumors in the Republic of Mali]. / Les tumeurs orbito-oculaires en République du Mali.

Analysing 82 cases of oculo-orbital tumours in Malian patients, the authors find the classical features characterizing ocular carcinoma in Africa, i.e. early arising, development, late request for treatment. They stress on the age of the patients at the occasion of the first request for treatment in case of retinoblastoma, and notice the special frequency of squamous cell carcinoma with conjunctival or limbic localization.

[Substance P: a peripheral inhibitor of gastric acid secretion in the rat]. / La substance P: un inhibiteur periphérique de la sécrétion gastrique acide chez le rat.

The inhibition of some peptidases in the central nervous system induces a decrease in gastric acid secretion. The present experiments indicate that substance P is not likely a candidate to mediate this effect in rats. Substance P, indeed, potently inhibits gastric acid secretion, but this effect appears mainly peripheral.