Daisuke Teshima

Nasal glucagon delivery using microcrystalline cellulose in healthy volunteers

We developed an intranasal powder form of glucagon to improve metabolic status and fatty liver in patients with pancreatectomy. Microcrystalline cellulose, which is commonly used in commercial preparations for allergic rhinitis was used as an absorption enhancer. We compared the intranasal powder form with some spray solutions of glucagon with regard to glucagon absorption, concentration of blood glucose, stability and nasal irritation. The absorption of glucagon from the spray solution including 1.5% sodium glycocholate or 1% sodium caprate was 1.3- and 2.6-fold higher than that from the powder form mixed with microcrystalline cellulose at a ratio of 1:69, respectively. The C(max) values of plasma glucose were 2.18, 3.39 and 1.56 mmol l(-1) in the spray solutions including sodium glycocholate and sodium caprate and in the powder form, respectively. However, glucagon in spray solutions was unstable, but that in the powder form was stable at 5 and 25 degrees C for at least 84 days. The spray solution caused strong irritation, but the powder form did not. These results suggested usefulness of the powder form of glucagon for treatment of pancreatectomized patients.

Clonal propagation of Cephaelis ipecacuanha.

Shoot cultures of Cephaelis ipecacuanha A. Richard were established by using shoot tips as initial explants. Multiple shoots were obtained from node segments upon culture on B5 medium supplemented with NAA-BA (0.01–3, 5 mg/l). These shoots were rooted on B5 and 1/2 MS media containing IAA or NAA, and the regenerated plants were transferred to soil and grown in a greenhouse. The emetic alkaloids of the regenerated plants, mother plants and leaves of shoot cultures were analyzed by TLC and HPLC. Seven months of growth under greenhouse condition, the contents of the emetic alkaloids in the regenerated plants were comparable to those of the mother plants.

Production of emetic alkaloid by in vitro culture of cephaelis ipecacuanha A. Richard

Callus and adventitious roots were induced on leaf segments from shoot culture of Cephaelis ipecacuanha A. Richard on Murashige-Skoog medium containing 2,4-dichlorophenoxyacetic acid, indole-3-acetic acid, 1-naphthaleneacetic acid and kinetin. The contents of emetic alkaloids in calli, roots and root suspension cultures were quantified by HPLC. Roots cultured in solid and liquid Murashige-Skoog media yielded emetine and cephaeline. The amount of the two alkaloids in the root suspension culture was very similar to that of roots from ipecac mother plant grown in a greenhouse. In contrast, calli subcultured on Murashige-Skoog media containing combinations of 2,4-dichlorophenoxyacetic acid and kinetin produced only trace amounts of emetic alkaloids.

A rapid and simultaneous determination of several analgesic antiinflammatory agents by capillary zone electrophoresis.

&NA; A rapid and simultaneous determination of several analgesic antiinflammatory agents—ibuprofen, acetaminophen, indomethacin, and salicylic acid—in human serum was developed by using capillary zone electrophoresis (CZE) coupled with diode‐array ultraviolet detection. After precipitation of serum protein with acetonitrile containing 3‐isobutyl‐1‐methylxanthine as the internal standard, an aliquot of deproteinized samples was applied directly to the CZE system. It enabled us to measure all of these four agents within 6 min, and there were no peaks interfering with the assay of these agents or 3‐isobutyl‐1‐methylxanthine. Both the separation and quantification of these agents in human serum were reproducible after repeated analysis within a day or day‐to‐day analysis. In addition, there was a good correlation for each drug (r = 0.997‐0.999) between the values in serum determined by CZE analysis and those measured either by high‐performance liquid chromatography with ultraviolet detection (ibuprofen and indomethacin) or by fluorescence polarization immunoassay (acetaminophen and salicylic acid). Therefore, the present CZE analysis could provide a simple, rapid, and efficient method for the identification as well as monitoring of analgesic antiinflammatory agents, particularly in serum of patients suffering from intoxication by overdosage of these agents.

Microanalysis of propofol in human serum by semi-microcolumn high-performance liquid chromatography with UV detection and solid-phase extraction.

Objective: To develop a simple analytical method for monitoring the low serum levels of propofol found when administered for the sedation of patients in the intensive care unit (ICU).

High-performance liquid chromatographic method for mycophenolic acid and its glucuronide in serum and urine

Objective:  To develop a simple analytical method for monitoring serum and urine concentrations of mycophenolic acid (MPA), an active metabolic constituent of the immunosuppressive pro‐drug mycophenolate mofetil, and its glucuronide.

Simple determination of mycophenolic acid in human serum by column-switching high-performance liquid chromatography

A column-switching high-performance liquid chromatographic analysis was established to monitor the serum concentration of mycophenolic acid, the active metabolite from mycophenolate mofetil administered for the prophylaxis of acute organ rejection in renal transplantation. The system consisted of two pumps for solvent delivery, a column-switching valve, a precolumn, and a reversed-phase analytical column. The present method enabled us to determine MPA by injecting serum samples directly into HPLC without any pretreatment. The mobile phases with different amounts of organic solvent were delivered to the precolumn and analytical column by separate lines, and samples were applied to the precolumn. The column switching valves were switched automatically following the processes for the elimination of protein and the drug analysis. The peak heights of MPA were linearly related to the concentrations (r=0.999) in the range of 0.1-20 micro g/ml, and the limit of quantification was 0.1 micro g/ml (S/N ratio=3). This method was accurate and reproducible on the basis of the results of recovery (94.0-98.0%) and small coefficient of variations of intra and inter-assay (less than 8.3%).

Usefulness of forced diuresis for acute boric acid poisoning in an adult

Background: Boric acid is generally not recognized as a poisonous substance. However, boric acid has potentially fatal actions such as hypotension, metabolic acidosis and oliguria. Death may result from circulation collapse and shock.

Sulphasalazine-induced leucopenia in a patient with renal dysfunction

Background: Sulphasalazine is used for the long‐term maintenance therapy of ulcerative colitis to prevent the relapse of symptoms. However, its clinical use is often restricted by its serious adverse effects.

Simple and simultaneous determination of sulphapyridine and acetylsulphapyridine in human serum by column-switching high-performance liquid chromatography

Objective:  A high‐performance liquid chromatography (HPLC) with an automated on‐line column‐switching system was used for the simultaneous determination of sulphapyridine and acetylsulphapyridine, two major active metabolites related to the adverse effects of sulphasalazine, in human serum.