Biomedical subjects

P Poitras

Publications and source records attributed to P Poitras.

At least 37 records · Page 2Linked to original sources

PubMed1994

Motilin synthetic analogues and motilin receptor antagonists.

While studying the structure-activity characteristics of motilin with motilin synthetic analogues, two compounds, motilin 1-12 [CH2 NH]3-4 and motilin 1-12 [CH2 NH]10-11, showed high affinity for the motilin receptor combined to a weak contractile activity. The following data suggest that motilin 1-12 [CH2 NH]10-11 is a potent motilin receptor antagonist. It showed a high affinity for the motilin receptor present on membranes of rabbit antrum (pIC50: 8.24 +/- 0.08 for the analogue vs 8.96 +/- 0.02 for the native peptide). When tested in vitro on strips of rabbit duodenum, the dose-response curve to motilin 1-22 was displaced to the right with motilin 1-12 [CH2 NH]10-11 (pIC50: 8.91 +/- 0.06 in presence of saline versus 7.19 +/- 0.40 with the analogue). However, when injected i.v. in dogs, motilin 1-12 [CH2 NH]10-11 was undetectable in the peripheral blood, suggesting enzymatic degradation precluding its use in vivo.

Animals↗

PubMed1994

Studies on the structure-activity of motilin in vivo. Effect of motilin synthetic analogues in conscious dog.

Synthetic analogues of motilin were tested for their capacity to stimulate the intestinal motor activity of the conscious dog. Physiological doses (75 pmol/kg) of motilin 1-22 and of motilin fragments 1-21, 1-20 and 1-19 induced premature periods of phase III activity in all tested animals. Motilin fragments 1-15, 1-12, 1-11 and 1-10 failed to influence the intestinal myoelectrical activity even when given at doses 10-times superior (750 pmol/kg). Motilin-like-immunoreactivity was measured in plasma during the analogues infusion. During the infusion of the bioactive analogues (1-22, 1-21, 1-20, 1-19), plasma motilin increased by 174 +/- 25 fmol/ml while a small rise (22 +/- 7.6 fmol) was noted with the inactive fragments (P < 0.001). Our data are in agreement with the in vitro findings that the N-terminal portion of the motilin molecule is responsible for its biological activity and suggests that the middle portion of the molecule is important to prevent degradation and maintain biological activity in vivo.

Animals↗

PubMed1994

Diarrhea and autonomic dysfunction in a patient with hexosaminidase B deficiency (Sandhoff disease).

The causal factors and the physiopathology of motor diarrhea are still unclear. This case report describes a 60-year-old white man with severe diarrhea for more than 10 years and minor signs of autonomic dysfunction. Extensive investigation showed that small intestinal motility and absorption were normal but that accelerated colon transit precluded water and solute absorption from the large bowel. Orthostatic hypotension, sexual dysfunction, and loss of sweating suggested dysfunction of the autonomous nervous system, which was confirmed by reduced plasma concentrations of norepinephrine and dopamine. Rectal biopsy specimens showed enlarged enteric ganglion cells filled with lipidic material. Levels of total hexosaminidase and hexosaminidase B in plasma, white blood cells, and fibroblasts were decreased, as found in Sandhoff disease. The pedigree of the proband's family showed several affected and heterozygous individuals, detected by examination of total hexosaminidase and hexosaminidase B levels in plasma. Among the five homozygous subjects, three had a clinical picture of diarrhea and orthostatic hypotension since the age of 50. Therefore, hexosaminidase B deficiency should probably be regarded as a cause for dysautonomia; dysfunction of the gastrointestinal tract, manifested by motor diarrhea or esophageal dysmotility, could be the initial and prevalent presentation of dysautonomia.

Autonomic Nervous System Diseases↗

PubMed1994

In vitro viability of cryopreserved equine embryos following different freezing protocols.

The main objective of this study was to evaluate two freezing protocols and the effect of agar embedding on survival of day 6.5 equine embryos. A total of 133 embryos were used, in one group (n = 51), embryos were first embedded in agar before the freezing protocol was started. A freezing protocol to -30 degrees C or -33 degrees C was used before plunging embryos into liquid nitrogen (LN2). The embryos were thawed in water at 37 degrees C, evaluated and placed in culture. After 24 h culture, the embryos were evaluated for their morphology and development. No differences were observed between embryos plunged at -30 degrees or at -33 degrees C in LN2. The analysis of the morphology and development after thawing showed that the diameter and developmental stage at freezing correlated with embryo survival. Morula and early blastocyst stages of development were associated with better quality after freezing and thawing and had a better potential to survive after in vitro culture (p < 0.05) compared to more advanced stages. The agar failed to protect embryos from zona pellucida damage, but a tendency to prevent rupture was observed in larger embedded embryos.

Animals↗

PubMed1993

Steroid synthesis by equine conceptuses between days 7 and 14 and endometrial steroid metabolism.

The objective of this study was to determine if changes in steroid synthesis occurred in the horse blastocyst about the time of maternal recognition of pregnancy. Embryos collected between days 7.5 and 14.5 were incubated for 8 hr in vitro in HAM's F10 containing radiolabelled pregnenolone. The steroid metabolites in the incubation medium were separated by reverse phase HPLC and the major peaks expressed as a percentage of total metabolites. It was found that there were no major changes in the profile of metabolites throughout the period of study, although there was increased conversion as the conceptuses developed. It was found that the major metabolite produced was 17 alpha-hydroxyprogesterone and not estradiol as expected. A second experiment was conducted to determine if 17 alpha-hydroxyprogesterone was metabolized by endometrial tissue. Endometrial biopsies from anestrous mares and from pregnant and nonpregnant mares at day 11 were incubated with radiolabelled 17 alpha-hydroxyprogesterone, progesterone or pregnenolone. The 17 alpha-hydroxyprogesterone, but not progesterone nor pregnenolone, was converted to a more polar metabolite in all groups. Production of this metabolite was significant greater in the anestrous mares. This metabolite has not been unidentified conclusively. Thus, results of this study show that 17 alpha-hydroxyprogesterone is the major steroid synthesized by the equine blastocyst and that this steroid is further metabolized to an unidentified steroid by the endometrium. These steroids could play a role in conceptus development or maternal recognition of pregnancy.

17-alpha-Hydroxyprogesterone↗

PubMed1992

Gastric inhibitory polypeptide-dependent cortisol hypersecretion--a new cause of Cushing's syndrome.

BACKGROUND: Corticotropin-independent nodular adrenal hyperplasia is a rare cause of Cushing's syndrome, and the factors responsible for the adrenal hyperplasia are not known. METHODS: We studied a 48-year-old woman with Cushing's syndrome, nodular adrenal hyperplasia, and undetectable plasma corticotropin concentrations in whom food stimulated cortisol secretion. RESULTS: Cortisol secretion had an inverse diurnal rhythm in this patient, with low-to-normal fasting plasma cortisol concentrations and elevated postprandial cortisol concentrations that could not be suppressed with dexamethasone. The cortisol concentrations increased in response to oral glucose (4-fold increase) and a lipid-rich meal (4.8-fold increase) or a protein-rich meal (2.6-fold increase), but not intravenous glucose. The infusion of somatostatin blunted the plasma cortisol response to oral glucose. Intravenous infusion of gastric inhibitory polypeptide (GIP) for one hour increased the plasma cortisol concentration in the patient but not in four normal subjects. Fasting plasma GIP concentrations in the patient were similar to those in the normal subjects; feeding the patient test meals induced increases in plasma GIP concentrations that paralleled those in plasma cortisol concentrations. Cell suspensions of adrenal tissue from the patient produced more cortisol when stimulated by GIP than when stimulated by corticotropin. In contrast, adrenal cells from normal adults and fetuses or patients with cortisol-producting or aldosterone-producing adenomas responded to corticotropin but not to GIP. CONCLUSIONS: Nodular adrenal hyperplasia and Cushing's syndrome may be food-dependent as a result of abnormal responsiveness of adrenal cells to physiologic secretion of GIP. "Illicit" (ectopic) expression of GIP receptors on adrenal cells presumably underlies this disorder.

Adrenal Glands↗

PubMed1992

N-terminal portion of motilin determines its biological activity.

This study aimed to identify the portion of the 22 amino acid sequence of motilin responsible for the biological activity of the peptide. The contraction of rabbit duodenal muscle in vitro was measured when exposed to synthetic fragments of motilin corresponding to various sequences of the C- or N-terminal portions of the molecule. Fragments 2-22 or 3-22 (where the initial amino acids of the N-terminal ending were removed) were more than 1000 times less potent than the native molecule 1-22. Fragment 1-9 (where the last 13 amino acids located at the C-terminal side of motilin were removed) was devoid of any contractile capacity, while synthetic fragments whose C-terminal structure extended beyond the 1-9 motilin sequence maintained almost complete biological activity. N-terminal amino acid sequence 1-9 is therefore an essential determinant of the contractile activity of motilin.

Animals↗

PubMed1992

Mechanisms for postprandial release of motilin in humans.

Plasma concentrations of motilin rise in the first 30 min following the ingestion of a meal in man. To elucidate the mechanisms of this postprandial motilin release, we verified the effect of cerebral stimulation and of gastric distension, both events normally occurring in the early postprandial period, on plasma motilin concentrations. Cerebral stimulation was induced by modified sham feeding (MSF) and gastric distension was done by inflating (with 0, 60, 240, or 480 cc of air) a latex balloon positioned in the gastric fundus. The experiments were performed in healthy volunteers where antroduodenal contractile activity was continuously recorded and where plasma motilin was measured each 10 min. The stimuli were administered 30 min after a phase III of the migrating motor complex (MMC) was seen migrating from the antrum to the duodenum. The interval period between two successive spontaneous peak increases in plasma motilin was estimated at 113.7 +/- 8.5 min in 24 historical control subjects, and it lasted 97 +/- 13 min in the five control volunteers here distended with 0 cc of air (P = NS). This interval was significantly (P < 0.05) shortened with MSF (70 +/- 6.3 min) or following distension with 60 cc (60 +/- 11.4 min), 240 cc (54 +/- 1.9 min) or 480 cc of air (45 +/- 3.2 min). During the 60-min period following the administration of the stimuli, phase IIIs were not seen in the subjects distended with 0 cc of air or in those submitted to MSF.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1992

Motilin and the postprandial motility of the antrum.

This study was designed to establish whether the rise in plasma motilin observed after a meal in humans can influence the postprandial motor activity of the antrum. Antroduodenal postprandial motility profiles and indices obtained from 5 controls and 5 subjects infused with exogenous synthetic motilin (0.1 microgram.kg-1) or with the motilin receptor agonist erythromycin lactobionate (200 mg) were compared. Motilin infusion increased plasma motilin concentrations about 5 times above the physiological range but failed to modify the normal postprandial contractile response. On the other hand, in 4 of the 5 subjects, erythromycin induced an intense motor response that mimicked phase III of the migrating motor complex. Our study demonstrates that, during the postprandial period, motilin antral receptors can be stimulated only with doses of motilin exceeding the physiological plasma concentrations, and that the motor effect obtained did not mimic the usual postprandial motility pattern. Our results, therefore, do not support the proposal that the postprandial motility of the antrum is regulated by the plasma levels of motilin.

Adolescent↗

PubMed1990

Stimulation of duodenal muscle contraction by porcine or canine motilin in the dog in vivo.

Motilin is a 22 amino acid polypeptide stimulating intestinal muscle contraction. Structure analysis of motilin purified from hog and from dog intestinal mucosa reveals different amino acids in positions 7, 8, 12, 13, and 14. Previous in vitro experiments suggested this species-related structural heterogeneity could generate different bioactive characteristics for these two peptides. This study was designed to compare the stimulatory mechanism of canine and porcine motilins on dog duodenal motility in vivo, testing the hypothesis that canine motilin stimulates a receptor located on the intestinal muscle, while porcine motilin is acting on intrinsic nerves regulating intestinal muscle contraction. Synthetic porcine and canine motilins were administered through a catheter inserted in the caudal pancreatic duodenal artery to stimulate the contraction of a close irrigated duodenal segment. In acute experiments performed on anaesthetized animals, both peptides induced a similar motor stimulation that was inhibited by tetrodotoxin and atropine. In experiments in conscious animals, canine and porcine motilins were equally potent in inducing premature phase III of the migrating motor complex, and the action of both peptides was abolished by atropine or hexamethonium. This study reveals that the structural heterogeneity between porcine and canine motilin does not influence the bioactivity of both peptides in the dog in vivo and suggests that circulating endogenous motilin stimulates intestinal muscle contraction through intrinsic excitatory nerves.

Anesthesia↗

PubMed1989

Regulation of plasma motilin by opioids in the dog.

In the first part of this study, we compared the effects of morphine and trimebutine, two opioid receptor agonists, on small intestinal motility and plasma motilin in dogs. Morphine (100 micrograms/kg iv for 10 min) induced first a typical vomiting myoelectric profile followed subsequently by a migrating electrical activity mimicking phase III of the migrating myoelectric complex; trimebutine (5 mg/kg iv for 10 min) initiated only a migrating phase III-like activity. Despite their different initial contractile effects, both agents induced a significant and similar rise in plasma motilin that preceded the beginning of the premature phase III. In the second portion of the study, naloxone, an opioid receptor antagonist, was infused to verify the influence of endogenous opiates on plasma motilin and on the migrating motor complex. Naloxone (2 mg/kg, then 0.5 mg.kg-1.h-1 iv) delayed significantly the cyclic recurrence of plasma motilin peak increases and of the phase IIIs. In some animals, where naloxone abolished the phase IIIs, the amplitude of the motilin peak increases was significantly diminished. These results suggest 1) that opioid administration increases plasma levels of motilin by a mechanism that is independent of the intestinal contractile activity, and 2) that endogenous opioids could be physiological inducers of plasma motilin increases in the conscious dog.

Action Potentials↗

PubMed1989

Molecular heterogeneity of human motilinlike immunoreactivity explained by the processing of prepromotilin.

Results of studies on the molecular forms of canine motilin suggest that this hormone might be synthesized as a higher molecular weight precursor, as is the case for most other biologically active peptides. Chromatographic analysis of human duodenal mucosa extracts and of human serum, using motilin-specific antibodies, also shows the presence of multiple forms of motilinlike immunoreactivity. Cell free translation of human duodenal messenger ribonucleic acid (mRNA) and immunoprecipitation of nascent peptides with motilin antibodies confirm that motilin is synthesized as a 14-15-kilodalton polypeptide precursor. Sequence of the human intestinal motilin complementary deoxyribonucleic acid (cDNA) demonstrates that this precursor bears a 25-amino acid signal peptide, a single dibasic cleavage site immediately following the 22 amino acids of human motilin, and a 65-amino acid polypeptide (motilin-related peptide) following this dibasic processing site. Southern analysis of human genomic kilobases DNA demonstrates that only one motilin gene is contained within 3.5-4 of human genomic DNA. Northern analysis of human intestinal RNA reveals one species of motilin mRNA of an estimated 700 nucleotides in length. These results suggest that (a) only one gene encodes the synthesis of human motilin in the different tissues where this polypeptide is synthesized; (b) human intestinal motilin is translated from one mRNA species and the resulting precursor is processed within the duodenal mucosa by sequential proteolytic cleavage first at a site within the motilin-related peptide, which results in the liberation of a 6-kilodalton form of motilinlike immunoreactivity, and then at the dibasic amino acid cleavage site, thus freeing motilin 22 from its precursor.

Amino Acid Sequence↗

PubMed1987

Motilin-like-immunoreactivity in intestine and brain of dog.

Motilin-like-immunoreactivity was detected in various regions of canine intestinal tract and brain. Its content in the brain was much smaller than in the gut. Its regional distribution was not uniform in both organs. On gel chromatography (G-50 SF), intestinal extracts revealed a main molecular form of motilin-like-immunoreactivity corresponding to motilin 1-22, while, in the brain, it eluted predominantly with the void volume. Further characterization of this later substance does not suggest it is strongly related to motilin. Putative motilin precursors of 14 kd and 6 kd are detectable in small concentration in intestinal mucosa.

Animals↗

PubMed1987

Comparative stimulation of motilin duodenal receptor by porcine or canine motilin.

Motilins purified from porcine and canine intestine differ in their amino acid composition in positions 7-8-12-13-14. We studied in vitro the contractile response of longitudinal duodenal muscles from various animals (guinea pig, rabbit, dog) to porcine and canine synthetic motilins. Both substances failed to elicit contraction of the guinea pig duodenum but were active and equally potent on rabbit muscle. In dogs, porcine motilin was inactive at the concentrations tested (up to 10(-4) M) whereas canine motilin induced duodenal contractions in a dose-response fashion (mean dose required to induce half-maximal response: 4.82 +/- 0.25 X 10(-5) M). The contraction generated by synthetic canine motilin (10(-5) M) was not influenced by atropine, hexamethonium, tetrodotoxin, naloxone, or sodium nitroprusside (all used at 10(-4) M) but was blocked by verapamil (10(-4)). Our study shows that species-related structural alterations in motilin molecules generate different bioactive capacities in some animal species, suggests that the middle portion of the molecule is important for its bioactive expression, suggests the presence of motilin receptors on canine duodenal muscle, and suggests that an influx of extracellular calcium is involved in the canine duodenal muscle contraction elicited by canine motilin.

Animals↗

PubMed1987

Indium-111 leukocyte scanning of the abdomen. Analysis of its value for diagnosis and management of inflammatory bowel disease.

Indium-111 leukocyte scanning of the abdomen (IAS) was performed in 10 patients with ulcerative colitis and in 39 patients with Crohn's disease involving the small intestine (in 25 occasions) and/or the colon (17 cases). Radionuclide uptake by the gut was seen in 84% of the patients with active inflammation. We compared the extent of the disease displayed by IAS with the findings obtained by either radiological or endoscopic studies or at surgery. In two-thirds of the patients, the IAS gave an accurate evaluation of the extent of the disease (sensitivity 68%). False-positive IASs were not seen in small bowel disease (specificity 100%), but were observed on 4 occasions on the colon (specificity 86%). The intensity of the radionuclide uptake could not be correlated with the clinical activity of the disease as evaluated by the Crohn's disease activity index. These results suggest that IAS is not superior to the standard procedures used to detect and localize inflammatory bowel disease and that IAS cannot replace these techniques. However, the simplicity of IAS and the complete lack of complications associated with its use render it useful in the evaluation of the extent and distribution of inflammation in some patients, mainly those with severe disease in whom standard diagnostic procedures would be contraindicated.

Abdomen↗

PubMed1987

Interdigestive intestinal motility in dogs with chronic exclusion of bile from the digestive tract.

To elucidate the role of bile delivery into the duodenum on the regulation of plasma motilin and on the interdigestive migrating complex, three dogs were operated upon to ligate the main bile duct and divert the biliary flow into the urinary bladder via a Foley catheter. After the operation, despite the chronic diversion of bile from the digestive tract, all animals maintained an excellent health status and exhibited recurrent periods of phase III motor activity migrating from the duodenum to the ileum, which were associated with cyclic increases in plasma motilin. Following the infusion of pooled dog bile (1 mL/min for 10 min) into the duodenum, a premature phase III and a concomitant rise in plasma motilin were observed. These results suggest, that although bile delivery into the duodenum can induce motilin increase in plasma and period of phase III activity in the gut, this phenomenon does not constitute an essential stimulus for the release of motilin and for the induction of the phase III of the interdigestive migrating complex.

Animals↗

PubMed1987

[Effect of trimebutine on the plasma postprandial release of gastrointestinal hormones in the dog].

The injection of trimebutine induces in the dog an increase of plasma motilin during the fasting period as well as after a meal. We studied the effect of trimebutine on several gastrointestinal hormones released into the circulation by the ingestion of a meal. The intravenous administration of trimebutine (10 mg/kg/h) in 4 dogs abolished the postprandial increase in plasma gastrin, pancreatic polypeptide, insulin, glucagon and GIP. Trimebutine could therefore, by its effects on various regulatory peptides, influence several digestive functions. Its mode of action could probably involves complex mechanisms, including paradoxical effects. The possibility that motilin is a mediator of the trimebutine effect on small bowel smooth muscle is discussed.

Animals↗

PubMed1987

[Endorphin control of blood motilin and the gastrointestinal motor complex in the dog].

To evaluate the role of endogenous opiates in the regulation of plasma motilin and the interdigestive motor complex of the small bowel, naloxone was administered in dogs. During the infusion of the opiate antagonist, the frequency of motilin cyclic release and of the motor complex was decreased. Moreover, with naloxone, peak increases in plasma motilin were similar to those measured during the control period in 5 of the 8 experiments. They were lower in 3 occasions. These results suggest that endogenous opiates do not play an essential role in the basal organization of intestinal interdigestive motility but that they are able to modify the frequency and the amplitude of motilin cyclic release. They support the possibility that endogenous opiates could, in some circumstances, exert a significant influence on the motor activity of the small intestine.

Animals↗