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Biomedical subjects

M Matsuoka

Publications and source records attributed to M Matsuoka.

At least 19 recordsLinked to original sources

Studies on pyridonecarboxylic acids. 1. Synthesis and antibacterial evaluation of 7-substituted-6-halo-4-oxo-4H-[1,3]thiazeto[3,2-a]quinoline-3- carboxylic acids.

A series of [1,3]thiazeto[3,2-a]quinoline-3-carboxylic acids and their esters were prepared and evaluated for antibacterial activity. The derivatives with a hydrogen or methyl group at C-1, fluorine at C-6, and piperazinyl or 4-methyl-1-piperazinyl group at C-7 showed superior in vitro antibacterial activity, and the derivatives with 4-methyl-1-piperazinyl group at C-7 had potent in vivo activity. Compound 29a (NM394) showed excellent in vitro antibacterial activity and low toxicity but poor absorption from the gastrointestinal tract. Compound 29ee (NM441), an N-[(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl] derivative of 29a, was found to possess a favorable pharmacokinetic profile and oral activity superior to that of ciprofloxacin in experimental animals.

Administration, Oral

[Pregnancy in Cushing's syndrome].

Pregnancy in cases of Cushing's syndrome is rare. A pregnant patient with Cushing's syndrome due to an adrenal adenoma who was diagnosed in the third trimester is described. She underwent conservative treatment for Cushing's syndrome and delivered a normal infant by Caesarean section. Currently, 121 pregnancies in 97 patients have been reported, but a principle for the treatment of the mother and fetus has not yet been established. We reviewed pregnancy in Cushing's syndrome based on the world literature and evaluated the choice of treatment to take. In the first trimester of pregnancy, therapeutic abortion or surgical treatment, such as adrenalectomy or resection of the pituitary tumor in Cushing's syndrome, is recommended for patients with severe hypercorticism (plasma cortisol > or = 30 micrograms/dl, urinary 17-OHCS > or = 15 mg/day, urinary free cortisol > or = 1000 micrograms/day), while conservative treatment is recommended for patients with mild hypercorticism (plasma cortisol < 30 micrograms/dl, urinary 17-OHCS < 15 mg/day, urinary free cortisol < 1000 micrograms/day). In the second trimester of pregnancy, surgical treatment is recommended for patients with severe hypercorticism, while conservative treatment is recommended for patients with mild hypercorticism. In the third trimester of pregnancy, Caesarean section is recommended for most cases. Drug treatments such as with metyrapone should be limited to patients showing severe hypercorticism or a maternal high risk who have contraindications to surgical treatment.

Adenoma

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

Preservation of energy metabolites by carnitine in the mouse brain under ischemia.

Ischemia (decapitation) caused marked changes of energy metabolites in the mouse brain. However, the changes were clearly less severe, when the mouse was pre-treated with L-carnitine. This suggests that L-carnitine may protect the brain from the ischemic attack. Since D-carnitine showed a similar effect, the effects may be due to mechanism(s) other than the 'classical' function of carnitine.

Animals

[Effects of methylmercury chloride on creatine kinase activity in the rat brain].

The effects of methylmercury chloride (MMC) on creatine kinase (CK) activity in the rat brain were studied. Male Wistar rats were injected subcutaneously with 10 mg MMC/kg body weight/day for 7 consecutive days, and sacrificed on the 15th day when all rats showed a crossing phenomenon of the hind limbs. CK activity was mildly inhibited in the anterior, mid and posterior cerebral cortex. Aspartate aminotransferase and lactate dehydrogenase activities were also inhibited in some parts of the cerebral cortex, almost to the same extent as the CK activity. No definite inhibition of the enzyme activity was found in the striatum and the cerebellum. From this study we concluded that the mild inhibition of CK activity does not seem to play an important role in the genesis of neurotoxicity of MMC.

Animals

Immunoglobulin V gene replacement is caused by the intramolecular DNA deletion mechanism.

Circular DNA resulting from V gene replacement was studied with an A-MuLV transformed cell line containing ablts. This cell line undergoes V gene replacement at elevated temperatures in the immunoglobulin (Ig) heavy chain (H) gene. Examination of circular DNA revealed that a heptamer-related sequence (TACTGTG) within the coding region of VDJ was joined to the recombination signal sequence (RSS) of a germline VH segment. This provides direct evidence for a intramolecular DNA deletion mechanism for V gene replacement. In the pre-B cell line as well as in in vivo lymphocytes, unusual circular DNAs were found which were structurally similar to the V gene replacement circles. They represented excision products of the deletion type recombination between one complete RSS and a heptamer-like sequence in the Ig H region.

Animals

Calculous pyelonephritis.

The authors report on 48 patients with calculous pyelonephritis. Urinary obstruction was caused by renal calculi in 21 patients and ureteral calculi in 27. Urine cultures were positive in 87.5% and bacteremia was seen in 70%. The common organisms in urine and blood culture were E. coli, Proteus and Klebsiella. Septic shock occurred in 10 (20.8%) out of 48 patients. Calculous pyelonephritis with urinary obstruction is a very serious condition.

Female

Spontaneous peripelvic extravasation of urine.

Spontaneous peripelvic extravasation of urine is relatively uncommon. We experienced 11 cases of spontaneous peripelvic extravasation. Urinary obstruction was caused by calculi in 9 cases, invasion by sigmoid carcinoma in 1 case and ureteral tumour (transitional cell carcinoma) in 1. Six patients presented with signs of peritonitis and 4 out of 9 with calculus did not develop microhaematuria. It is important to differentiate peripelvic extravasation from other acute abdominal conditions. We must pay special attention to patients with signs of peritonitis and normal urinalysis.

Female

Brain energy metabolites in mice intoxicated with acrylamide: effects of ischemia.

Concentrations of phosphocreatine, creatine, ATP, ADP, AMP, glucose and lactate in the whole brain did not differ between the mice intoxicated with acrylamide and the controls. When the brain was made ischemic, these concentrations changed to the same extent in both groups. The only difference was the lower pyruvate in acrylamide-intoxicated mice under the ischemia. Thus, as far as the whole brain is concerned, acrylamide does not cause gross alterations of energy metabolites, even under ischemia.

Acrylamide

Inducible resistance to a 16-membered macrolide, mycinamicin, in Staphylococcus aureus resistant to 14-membered macrolides and streptogramin B antibiotics.

Staphylococcus aureus 8325(pEP2104), a transductant derived from S. aureus PM2104 isolated clinically in Hungary (L. Janosi, and E. Ban, Acta Microbiol. Acad. Sci. Hung., 29: 187-200, 1982), exhibited an inducible resistance to the 14-membered macrolides [erythromycin (EM) and oleandomycin (OL)] and streptogramin B (MKM-B) antibiotics, but not to the 16-membered macrolides and lincosamides. This resistance was referred to as PMS-resistance phenotype (L. Jánosi, Y. Nakajima, and H. Hashimoto, Microbiol. Immunol., 34: 723-735, 1990). In addition to EM, OL, and MKM-B, however, the strain was recently and first observed to have inducible resistance to mycinamicin, a 16-membered ring macrolide. Thereby, we propose that the reference stated just above as PMS-resistance has to be extended to such 16-membered macrolides as mycinamicin. An optimum concentration of erythromycin or oleandomycin for induction of PMS-resistance was 1.35 mu g/ml in the strain 8325(pEP2104). The concentration was about 30 times as great as that (0.05 mu g/ml) required for induction of well-known co-resistance to macrolide-lincosamide-streptogramin B antibiotics in S. aureus ISP447.

Anti-Bacterial Agents

[Elucidation on abnormal behavior of glycyrrhizin salts in high performance liquid chromatography determination for quasi-drug products].

Glycyrrhizinates such as monoammonium and dipotassium glycyrrhizinates which are extracted from licorice, converted to easily water-soluble salts and refined have been formulated in many quasi-drug products as an anti-inflammatory agent. A quantitative analysis of glycyrrhizinates in quasi-drug products has usually and successfully been carried out by high performance liquid chromatography (HPLC). However, a slightly higher value than the actual content has sometimes been observed in daily analysis. As the result of our various studies to investigate these phenomena, we finally found that a minor constituent in commercial glycyrrhizinates, which was identified as monomethyl glycyrrhizinate, was hydrolyzed after they were formulated in quasi-drug products and converted to glycyrrhizin which in turn was determined by HPLC as a higher value.

Chromatography, High Pressure Liquid

Blood levels and urinary excretion of thiamin and riboflavin during oral administration of multivitamin tablets to healthy adults.

1. The baseline blood thiamin concentration increased gradually during the long-term administration of TTFD, and the blood concentration was dose-dependent. The cumulative urinary thiamin excretion showed the same dose-dependence as the blood concentration. 2. The baseline blood riboflavin concentration also increased steadily during the administration period, but the increase was less than that of thiamin. Dose-dependence of the cumulative urinary excretion of riboflavin was noted. 3. No side effect were observed.

Administration, Oral

[A case of aortitis syndrome treated by simultaneous procedure of Bentall's operation and aortic arch replacement].

The case is a 22-year-old man, in whom chest X-P pointed out aortic and cardiac shadow enlargements. Aortography revealed extensive aortic aneurysm involving the ascending, arch, and proximal descending portions of the aorta, accompanied with annulo-aortic ectasia, aortic regurgitation, and stenosis of the left common carotid and left subclavian arteries, suggesting lesions due to aortitis syndrome. For this case, Bentall's operation and replacement of the aortic arch and the proximal descending aorta were performed simultaneously, using hypothermic selective cerebral perfusion. Favorable postoperative course and absent neurological abnormality enabled the patient to return to his former social work. Steroid therapy has been continued up to the present, 5 years postoperatively, with neither recurrence of inflammation nor occurrence of cardiac murmur.

Adult

Suppression of neurotoxicity of ammonia by L-carnitine.

Administration of ammonium acetate to mice caused seizures and alterations of brain energy metabolites. Pretreatment of animals with L-carnitine suppressed the frequency of the seizures and prolonged the latency to the first fit. When examined using the 'freeze clamp' method, brain energy metabolites were well preserved and the elevation of ammonia was less marked on administration of L-carnitine. Thus, L-carnitine suppresses ammonia-induced seizures and biochemical alterations of the brain in mice.

Ammonia