Nobuhiro Ikei

Elevation of plasma CCK concentration after intestinal administration of a pancreatic enzyme secretion-stimulating peptide purified from rat bile-pancreatic juice: Analysis with N-terminal region specific radioimmunoassay

The rat plasma cholecystokinin (CCK) concentration was measured after intestinal administration of a peptide purified from rat bile-pancreatic juice, which has a stimulatory effect on pancreatic enzyme secretion. The plasma CCK concentration was measured by means of a radioimmunoassay using CCK-8 N-terminal specific antibody, OAL-656. In experimental rats with protease-free intestines, intraduodenal infusion of 10 micrograms of the purified peptide, which stimulates pancreatic enzyme secretion 2.0-2.5 fold, induced a significant increase in the plasma CCK level. Furthermore, after removal of CCK from the plasma by immunoabsorption with an OAL-656-bound Sepharose 4B column, the stimulatory effect of the plasma on pancreatic enzyme secretion was abolished when it was injected intravenously into recipient rats. It was concluded that this peptide stimulates the release of CCK in the intestine and that this is responsible at least in part for the pancreatic enzyme secretion-stimulating activity of the peptide.

Meal-stimulated cholecystokinin release and exocrine pancreatic secretion in dogs.

SummaryTo confirm the role of cholecystokinin (CCK) and secretin in digestion, exocrine pancreatic secretion, plasma CCK, and secretin were measured simultaneously in six dogs prepared with gastric and pancreatic fistulas after feeding a solid meal. Plasma CCK concentration determined by radioimmunoassay increased significantly from the basal level, reached a peak 35 min after meal ingestion, and after a dip it further increased toward the end of the 3-h observation. Pancreatic protein output increased significantly, peaked at the fifth 10-min period, and then declined progressively. Plasma CCK concentration and pancreatic protein output correlated significantly during the first postprandial hour. Plasma secretion demonstrated significant elevation at 15 min and a peak at 25 min after a meal. Plasma secretin correlated significantly with both bicarbonate output and flow rate during the 3h. Simultaneous measurements of plasma CCK and secretin and of pancreatic secretion suggested that postprandial pancreatic secretion is primarily mediated by releases of CCK and secretin, but these hormones do not seem to be the only factors responsible for the secretion.

Effects of viscosity on power and hand injection of iso-osmolar iodinated contrast media through thin catheters.

Background It can be challenging to achieve adequate vessel opacification during percutaneous coronary interventions when using thin catheters, hand injection, and iso-osmolar contrast media (CM) such as iodixanol (Visipaque™). Purpose To explore these limitations and the possibility to overcome them with iosimenol, a novel CM. Material and Methods Three X-ray contrast media with different concentrations were used in this study. A series of in vitro experiments established the relationship between injection pressure and flow rate in angiography catheters under various conditions. The experiments were conducted with power and hand injections and included a double-blind evaluation of user perception. Results By using hand injection, it was generally not possible to reach a maximum injection pressure exceeding 50 psi. The time within which volunteers were able to complete the injections, the area under the pressure-time curve (AUC), and assessment of ease of injection all were in favor of iosimenol compared with iodixanol, especially when using the 4F thin catheter. Within the pressure ranges tested, the power injections demonstrated that the amount of iodine delivered at a fixed pressure was strongly related to viscosity but unrelated to iodine concentration. Conclusion There are substantial limitations to the amount of iodine that can be delivered through thin catheters by hand injection when iso-osmolar CM with high viscosity is used. The only viable solution, besides increasing the injection pressure, is to use a CM with lower viscosity, since the cost of increasing the concentration, in terms of increased viscosity and consequent reduction in flow, is too high. Iosimenol, an iso-osmolar CM with lower viscosity than iodixanol might therefore be a better alternative when thinner catheters are preferred, especially when the radial artery is used as the access site.

Physicochemical Properties of Radiographic Contrast Media, Potential Nephrotoxicity and Prophylaxis

Contrast induced nephropathy (CIN) remains a controversial topic. The clinical relevance of changes in laboratory parameters has been challenged; some authors have even suggested that CIN simply reflects natural fluctuations. Other areas of controversy include the pathophysiology of CIN, effectiveness of prophylactic approaches and differences in nephrotoxicity between individual contrast media (CM). The aim of this review is to summarize the current understanding of laboratory findings and explore its relationship to CM toxicity.

Analysis of seven pedigrees of childhood Wilson's disease characterized by abdominal symptoms.

In a survey of childhood Wilsons disease (WD) characterized by abdominal symptoms, three patients with high levels of immunologically detectable ceruloplasmin (CP) in serum were found. These three cases were compared with typical cases of WD in which serum CP level was low. In order to clarify the cause of WD, serum CP levels were quantified by two methods, an immunological protein assay and an oxidase activity assay. Using the results of these two assays, WD cases were classified into three groups on the basis of CP content; the first group consisted of patients with low enzyme activity and low CP protein content, the second group consisted of patients with low enzyme activity and normal CP protein content, and the third group, those patients with normal enzyme activity and normal CP protein content. No significant difference in symptoms was observed between these three groups. Since relatively high levels of CP were detected in some WD patients, genetic variation in CP in WD patients was examined by restriction enzyme fragment length polymorphism analysis using CP cDNA. However, no large deletion in the CP gene was detected. Using four types of gene probes for chromosome 13 known to be related to WD, the DNA of WD patients was examined in a similar fashion, but no significant difference was observed between the groups.

Stimulatory Effects of Bombesin on Plasma Trypsin Release and Exocrine Pancreatic Secretion in Dogs

We examined the effect of bombesin on plasma trypsin release and exocrine pancreatic secretion in dogs. Bombesin significantly increased plasma immunoreactive trypsin (IRT). Atropine significantly inhibited the response of plasma IRT to bombesin. Pancreatic trypsin secretion was also increased by bombesin, as well as bicarbonate and protein outputs. Atropine failed to inhibit pancreatic trypsin secretion. In conclusion, bombesin has a stimulatory effect on plasma trypsin release mediated by a cholinergic mechanism and different from pancreatic secretion.

Hemodialysis clearance of iosimenol, a novel iso-osmolar radiographic contrast medium.

Background Iodinated contrast media (CM) have molecular and pharmacokinetic properties likely to make them highly dialyzable. Controlled clinical studies allowing for comparisons of hemodialysis clearance between different test substances and in multiple hemodialysis filters are, however, complex and not always practically feasible. A miniaturized in vitro method was therefore developed to evaluate the dialyzability of a new CM. Purpose To evaluate hemodialysis clearance of iosimenol, a novel iso-osmolar contrast medium (CM), in a select variety of hemodialysis filters and in comparison to commercially available CM. Material and Methods Three different high-flux and one low-flux membrane were used in miniaturized dialyzers to evaluate the in vitro blood clearance of iosimenol. Commercially available CM (iodixanol and iohexol) served as control substances. In vitro dialysis parameters were then used to predict clinical hemodialysis clearances. Residual ratios of endogenous substances (inorganic phosphate, urea nitrogen, creatinine, total bilirubin, and albumin) were used as proof of reliability of the in vitro dialysis system. Results Dialyzable small endogenous molecules were readily eliminated in all membranes. The removal ratios of iosimenol were generally similar to that of iodixanol in all membranes except the high-flux polysulfone but were consistently lower than that of iohexol. The blood clearance of iosimenol during clinical hemodialysis was predicted as, on average, approximately 85 mL/min with the high-flux membranes and 47 mL/min with the low-flux membrane. Conclusion The dialyzability of iosimenol was evaluated using a newly developed in vitro dialysis system, and iosimenol was readily cleared from blood with all four tested membranes. And it is suggested that the dialysis parameters can predict clinical hemodialysis clearance of CM.