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Biomedical subjects

M Mabuchi

Publications and source records attributed to M Mabuchi.

34 records · Page 2Linked to original sources

Rapid determination of a new angiotensin-converting enzyme inhibitor, imidapril, and its active metabolite in human plasma by negative-ion desorption chemical ionization-tandem mass spectrometry (MS/MS).

A very rapid and highly sensitive method using desorption chemical ionization (DCI)-tandem mass spectrometry (MS/MS) with selected reaction monitoring is reported for the simultaneous determination of imidapril and its active metabolite (M1) in human plasma. Imidapril and M1 in plasma were extracted by a C18 solid phase extraction cartridge after deproteinization, and derivatized with pentafluorobenzyl bromide. One microliter of prepared sample was applied to the DCI filament and analyzed by DCI/MS/MS within a few minutes. The limits of determination of imidapril and M1 were 0.2 and 0.5 ng/ml in human plasma, respectively. The features of this method make it appropriate for use in pharmacokinetic studies with human plasma after oral administration of imidapril.

Angiotensin-Converting Enzyme Inhibitors↗

Determination of three metabolites of a new angiotensin-converting enzyme inhibitor, imidapril, in plasma and urine by gas chromatography-mass spectrometry using multiple ion detection.

A specific and sensitive gas chromatographic-mass spectrometric method for the determination of three metabolites of the angiotensin-converting enzyme inhibitor, imidapril, in plasma and urine was developed. The metabolites were isolated from plasma and urine using a Bond Elut C18 solid-phase extraction cartridge. The isolated metabolites were converted to sensitive derivatives by pentafluorobenzyl bromide and heptafluoro-n-butyric acid anhydride. Following derivatization, the sample solutions were analysed by wide-bore column gas chromatography-mass spectrometry with multiple ion detection. The detection limits of the three metabolites were each 1 ng/ml in plasma and 5 ng/ml in urine. Analysis of the spiked plasma and urine samples demonstrated the good accuracy and precision of the method. This method was very useful for use in pharmacokinetic and bioavailability studies of the three metabolites of imidapril in humans.

Angiotensin-Converting Enzyme Inhibitors↗

Assay of nicergoline and three metabolites in human plasma and urine by high-performance liquid chromatography-atmospheric pressure ionization mass spectrometry.

A method for the simultaneous determination of nicergoline and three of its metabolites in human plasma and urine has been developed using high-performance liquid chromatography-atmospheric pressure ionization mass spectrometry. Nicergoline and its metabolites were extracted from the plasma and urine samples with chloroform and separated on a reversed-phase ODS column. The eluents were led to the atmospheric pressure ionization interface and then analysed in the selected-ion monitoring mode. The detection limits of nicergoline and three of its metabolites were ca. 2 ng/ml in plasma and ca. 10 ng/ml in urine, at a signal-to-noise ratio of 4.

Chromatography, High Pressure Liquid↗

Metastatic vulvar Paget's disease responding to combination chemotherapy: case report.

No effective chemotherapy for advanced extramammary Paget's disease has yet been established. A case of vulvar Paget's disease with systemic metastases was treated with a mitomycin C, vincristine and cisplatin combination chemotherapy, by which the vulvar lesion and serum CEA were clearly decreased. After surgery and 5-fluorouracil treatment, a similar combination chemotherapeutic regimen was administered to treat a recurrence, however, the lesions became resistant.

Aged↗

[Fundamental and clinical evaluation of cefodizime in obstetrics and gynecology].

Cefodizime (CDZM, THR-221), a newly developed injectable cephem antibiotic agent, was evaluated for its distribution in intrapelvic genital organ tissues, penetration into exudate of retroperitoneal space and breast milk and therapeutical effects on some infections in obstetrics and gynecology. The results obtained are summarized as follows. 1. When 1 g of CDZM was administered by drip infusion over a 60 minutes period, its serum concentration reached 53.51 micrograms/ml at the completion of drip infusion, then declined rapidly. Peak concentrations of CDZM in intrapelvic genital organ tissues were higher than 20 micrograms/g at different times. CDZM was transferred to the exudate of retroperitoneal space and its concentration reached a peak of 7.01 micrograms/ml at 2.67 hours after initiation of 60 minutes drip infusion at a dose of 1 g, then declined slowly but stood at 4.93 micrograms/ml even at 8 hours. The transfer of CDZM to breast milk was similar to other cephem antibiotic agents and peak levels of CDZM in milk were 0.13-0.36 microgram/ml at 2 or 3 hours after administration of a dose of 1 g. 2. In the clinical study, CDZM was administered by drip infusion over 60 minutes to 6 patients with obstetrical and gynecological infections at a daily dose of 2-6 g. Clinical results were good in 5, poor in 1, and the efficacy rate was 83.3%. No side effects nor abnormal laboratory test results were observed.

Adult↗

Malignant thymoma associated with liposarcoma of the mediastinum--a case report.

Malignant thymoma occurring concurrently with mediastinal liposarcoma in a 49-year-old man is described. The patient underwent an incomplete resection of the mediastinal mass followed by irradiation therapy and additional chemotherapy. He died about 9 months after the detection of a mediastinal mass on chest X-ray films and the immediate cause of death was superior vena cava syndrome. The incidence of primary liposarcoma of the mediastinum alone is extremely rare. Only a few more than 20 with such a lesion have been documented in Japan. A review of the literature of patients with mediastinal liposarcoma and thymoma associated with malignancies revealed no case of an association of thymoma and liposarcoma.

Humans↗

Sequential hepatic changes during sterigmatocystin-induced carcinogenesis in the rat.

The effect of protein deficiency on the hepatotoxicity and carcinogenicity of sterigmatocystin was studied in rats. Sterigmatocystin, 500 ppm/day, fed in a regular diet induced marked toxic effects and there was a high incidence of hepatocellular carcinoma and hyperplastic nodules. The same dosage fed in a protein-deficient diet produced toxic signs followed by a high incidence of death within 27 weeks. Surviving animals showed dysplastic liver cell changes but no tumors were noted. The incidence of hepatocellular carcinoma was 87% in rats receiving 15 ppm of the substance per day for 200 days in a protein-deficient diet. Sequential histologic and histochemical studies revealed that hyperplastic and preneoplastic liver lesions appeared at 28--32 weeks after inseption of the sterigmatocystin-supplemented diet. No cirrhotic changes and only transient fibrosis were noted. The morphogenesis of the sterigmatocystin-induced lesions was compared with that of aflatoxin B1-induced lesions.

Animals↗

Induction of bone loss by bile duct ligation in rats.

Metabolic bone loss is the most common complication of chronic liver disease. However, there is little information available about bone loss in rats with a ligated bile duct, a biliary-type of experimental cirrhosis model. Therefore, in this study, the effect of bile duct ligation (BDL) on bone mineral density (BMD) and plasma insulin-like growth factor-I (IGF-I) levels was examined in rats. Two weeks after BDL operation, the rats with a ligated bile duct showed a pronounced and significant decrease in both trabecular and cortical BMD of the femur. In these rats, decreases in food intake and plasma IGF-I levels plus elevated levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and bilirubin were also observed. When the effect of dietary restriction (30% or 50%) over 2 weeks was then investigated in normal rats, 50% food restriction resulted in a significant decrease in femoral trabecular bone density although BMD was unchanged by 30% dietary restriction. The plasma levels of IGF-I were also decreased in food-restricted rats. Thus, the decrease in femoral bone density in 50% food-restricted rats was less potent compared with BDL rats; nevertheless, the decrease in plasma levels of IGF-I was almost equally potent in both BDL and food-restricted rats. Overall, this study showed that BDL operation resulted in a pronounced bone loss in rats, but also that this bone loss might not be merely due to the decreases in food intake and plasma IGF-I levels. These results suggest that BDL in rats is a useful experimental cirrhosis model for evaluating the bone loss associated with chronic liver disease.

Animals↗