Shinsuke Morimoto

HLA-DRB1*1502 allele, subtype of DR15, is associated with susceptibility to ulcerative colitis and its progression.

HLA-DRB1 allele typing was performed by the PCR-RFLP method on 59 ulcerative colitis (UC) patients and 136 healthy controls. Phenotypic frequencies of HLA-B52 and DR2 were significantly increased among the UC patients, serologically. DNA typing of HLA-DRB1 revealed that the genotypic frequency of DRB1*1502 was higher in UC than in the controls (49.2% vs 17.6%;P<0.0001). In the analysis of clinical parameters, 82.8% of patients bearing DRB1*1502 were treated with corticosteroids. DRB1*1501 and DRB1*1502 differ in only one amino acid at residue 86 (valine vs glycine), and 66% of the UC patients carried two glycines at position 86 in the HLA-DRβ-chain (vs 51% of control;P<0.05). These observations suggest that the presence of Gly-86 in the HLAβ-chain and surrounding amino acid sequence of HLA-DRB1*1502 is strongly associated with susceptibility to UC.

EM523L, a nonpeptide motilin agonist, stimulates gastric emptying and pancreatic polypeptide secretion

We investigated the efficacy and the mechanism of action of EM523L, a nonpeptide motilin agonist (motilide), on the stimulation of gastric emptying and on the release of gut peptides after ingestion of a solid meat in normal controls (n = 8) and in diabetic patients (n = 8) with signs of neuropathy. A dose of 2 mg EM523L was administered IV over 15 min just after ingestion of a solid meal (200 kcal Gastric emptying was measured by a radionuclide technique. EM523L accelerated gastric emptying and markedly augmented postprandial pancreatic polypeptide (PP) response in both normal control and diabetic patients. This may suggest the mediation of the Vagal-cholinergic pathway to accelerate gastric emptying. The present study offers a promising therapeutic potential of the motilide in gastrointestinal motility disorders like those observed in diabetics mellitus.

Effect of trimebutine maleate on emptying of stomach and gallbladder and release of gut peptide following a solid meal in man

We investigated the effect of orally administered trimebutine maleate on gastric and gallbladder emptying and on the release of gut peptide, pancreatic polypeptide (PP), and gastrin in humans for 120 min after ingestion of a solid meal. Gastric emptying was measured by a radionuclide technique. Gallbladder emptying was estimated by real-time ultrasonography. The oral administration of 200 mg of trimebutine maleate significantly shortened the lag time in starting gastric emptying (P<0.05). Considering gallbladder emptying, trimebutine significantly inhibited the fasting emptying induced by neural reflex. Postprandially, there was a tendency toward an accelerated gallbladder emptying in the early phase. Neither the maximal percentage of gallbladder emptying nor the time of peak gallbladder emptying were affected. Trimebutine significantly blunted the postprandial PP response in the cephalic and gastric phases, reflecting a vagal-cholinergic activity (P<0.05). The PP response in the intestinal phase was also blunted. Gastrin release was significantly augmented only during the period of fasting after drug administration (P<0.05). The major effect of trimebutine maleate appears to be a shortening of the lag time at the start of gastric emptying probably via its anticholinergic activity.

Effect of synthetic prostaglandin E1 analog (ornoprostil) on gastric emptying and pancreatic polypeptide release after solid-meal ingestion in man

The effect of orally administered ornoprostil, 17S,20-dimethyl-6-oxoprostaglandin E1 methyl ester, on gastric emptying and on pancreatic polypeptide (PP) release after solid meal ingestion, was investigated in man. A radionuclide technique was used to measure gastric emptying of eight healthy volunteers. In addition, four parameters [SI (starting index): the lag time in the start of emptying;K value: the emptying rate;T1/2: the half emptying time; 120 min RR: the percent retention at 120 min] were determined for evaluation. Also, the PP response was analyzed according to two parameters: IPPRSI, the integrated PP response for periods up to SI, and IPPR120, the integrated PP response for 120 min. The results demonstrated that 5 μg of orally administered ornoprostil significantly reduced the gastric emptying rate of solid meal (T1/2 and 120 min RR,P<0.05). However, ornoprostil affected neither the basal PP concentrations nor the cephalic phase of PP secretion which was determined as IPPRSI. This thus suggests that ornoprostil affects the gastric motor function without interfering with the vagal-cholinergic pathway to the stomach.