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Biomedical subjects

H Mizuta

Publications and source records attributed to H Mizuta.

At least 73 records · Page 4Linked to original sources

Effect of small intestinal transit time on gastrointestinal absorption of 2-[3-(3,5-di-tert-butyl-4-hydroxyphenyl)-1H-pyrazolo[3,4-b]pyridin-1-yl ] ethyl acetate, a new non-steroidal anti-inflammatory agent.

The gastrointestinal absorption of 2-[3-(3,5-di-tert-butyl-4-hydroxyphenyl)-1H-pyrazolo[3,4-b]pyridin-1- ly]ethyl acetate (1), a new non-steroidal anti-inflammatory agent was investigated in dogs. A method using acetaminophen and salicylazosulfapyridine as the markers (double-marker method) was applied to trace the gastrointestinal transit of orally dosed 1. The mean absorption time of acetaminophen in plasma was used as an indication of gastric emptying, and the first appearance time of sulfapyridine (a metabolite of salicylazosulfapyridine) in plasma was employed to detect the arrival of the marker to the colon. A remarkable inter-individual variation was observed in the absorption of 1. The extent of bioavailability was little affected by the gastric emptying time, but significantly influenced by the small intestinal transit time. Under a pretreatment with atropine, the transit time was prolonged to result in a significant enhancement of the bioavailability. Consequently, the absorption of 1 is confirmed to take place mainly in the small bowel.

Acetaminophen↗

[Effects of bile and meal on the gastrointestinal absorption of 2-[3-(3,5-di-tert-butyl-4-hydroxyphenyl)-1H-pyrazolo[3,4-b]pyridin- 1-yl]ethyl acetate, a new non-steroidal anti-inflammatory agent].

The effects of bile and meal on the gastrointestinal absorption of 2-[3-(3,5-di-tert-butyl-4-hydroxyphenyl)-1H-pyrazolo[3,4-b]pyridin - 1-yl]ethyl acetate (1), were investigated in rats and dogs. Compound 1 was lipophilic and soluble in bile, but extremely insoluble in water. The important role of bile in the dissolution step in the absorption process of 1 was confirmed on the in situ absorption study with rats. Oral absorption of 1 was insufficient and showed a marked individual difference in fasting dogs. When the same compound was administered after ingestion of a meal, the absorption increased with decreasing scatter. Three kinds of meals had different potencies to enhance the bio-availability of 1 in the order of lard greater than mashed potatoes greater than skimmed milk. The absorption behavior of 1 reflected small intestinal transit time and the stimulated bile output after ingestion of meal.

Animals↗

Molecular cloning and physical mapping of the DNA of Miscanthus streak geminivirus.

Molecular cloning and physical mapping of miscanthus streak virus (MiSV) circular double-stranded (ds) DNA was carried out. The circular dsDNA was isolated from leaves of Miscanthus saccariflorus (Gramineae) infected with MiSV. In addition to the monomeric circular dsDNA form in MiSV-infected leaves, there were minor circular dsDNA populations of twice (dimer) and approximately half genome length. The size of monomeric circular dsDNA was about 2.67 kilobase pairs. The evidence presented suggests that the genome of MiSV consists of one component.

Cloning, Molecular↗

Gastric pH profile and its control in fasting beagle dogs.

The gastric pH of fasting beagle dogs was measured by using an ion-selective field effect transistor pH sensor. In addition, a novel procedure to control the gastric pH in fasting beagle dogs was investigated. Inter- and intra-day variations in the gastric pH of the dogs were observed. The gastric pH of the dogs could be controlled by a single intravenous administration of omeprazole, an H+, K+-adenosine triphosphatase (ATPase) inhibitor (1 mg/0.25 ml/kg). The pH in the stomach was 6.6 +/- 0.2 (mean +/- S.D., n = 6) at 1 h after the omeprazole treatment, and this level of pH was maintained for a period of at least 3 h. Beagle dogs in which the gastric pH has been controlled by omeprazole are considered to be useful as an animal model to be used for the pharmaceutical evaluation of drugs in subjects with a low acidity level.

Animals↗

Effect of gastric acidity on bioavailability of N,N-dimethylcarbamoylmethylalpha, 2-dimethyl-5H-[1]benzopyrano[2,3-b]pyridine-7-acetate, a new prodrug-type anti-inflammatory agent.

The effect of gastric acidity on the bioavailability of N,N-dimethylcarbamoylmethyl alpha,2-dimethyl-5H-[1]benzopyrano[2,3-b] pyridine-7-acetate (1), a new anti-inflammatory agent, was investigated in gastric acidity-controlled beagle dogs. The dissolution rates of this compound in media of pH 1.2 and 3.0 were greater than those in media of pH 5.0 and 6.8. Reflecting these dissolution characteristics, the peak plasma concentration (Cmax) and the area under the plasma concentration-time curve (AUC0-12h) were reduced by shifting the gastric acidity to low levels (more than pH 6) with omeprazole treatment. In designing dosage forms of 1, it is necessary to develop pharmaceutical preparations whose bioavailability is not affected by the gastric acidity.

Animals↗

[Determination of small intestinal transit time in beagle dogs using salicylazosulfapyridine].

The method for the assessment of small intestinal transit time (SITT) in beagle dogs was investigated by using the time for the first appearance of sulfapyridine in the plasma (TFA) after oral administration of salicylazosulfapyridine (SASP). After administration of SASP into the small intestine or the cecum of anesthetized dogs, sulfapyridine (SP) was detected in the plasma only in the latter case. These results indicate that TFA could be an index of arrival time in the cecum, an index of SITT in dogs. A remarkable inter-individual variation of TFA was observed after oral administration of SASP to fasting dogs, and the mean value of TFA was about 3 h. As for intra-individual variation of TFA, both variable and less variable dogs were observed. TFA was prolonged significantly by atropine (0.1 mg/kg, i.v.) and shortened significantly by metoclopramide (0.5 mg/kg, i.v.). As the pharmacological modification of gastrointestinal motility was thus mirrored by TFA, SASP method is considered to be useful for the assessment of SITT in beagle dogs.

Animals↗

Avulsion of the hamstring muscles from the ischial tuberosity. A report of two cases.

In two rare cases with avulsion of the hamstring muscles from the ischial tuberosity without fracture of the ischium, the clinical features were: (1) sudden onset of pain in the buttock; (2) difficulty on standing after trauma; (3) a palpable defect and tenderness on the area distal from the ischial tuberosity; and (4) weakness of flexion of the knee with a loss of normal outline of the hamstring muscles on the dorsal aspect of the knee. There was no roentgenologic evidence of fracture of the ischium. Surgical repair with reattachment of avulsed muscles to the ischium and proximal tendinous sheaths of the muscles restored function or corrected deformity.

Adolescent↗

[A mild form of brain stem encephalitis due to herpes simplex virus].

A 10-year-old boy had gait and speech disturbances 17 days after the initial symptoms of a fever, headache and cough. Four days later he was admitted to a hospital with mild disturbances of gait, speech, writing, visual acuity, left facial nerve, nystagmus and consciousness. Impairments of cranial nerves (II, III and VII), pyramidal sign and cerebellar sign were noticed. EEG showed generalized slow waves. Auditory brain stem response showed prolongation of the interval between I and V waves and poor differentiation between them. Brain CT could not find any abnormalities. Brain stem encephalitis was diagnosed. Clinical signs and symptoms continued for two weeks when steroid therapy was started and it was effective to improve the disease. He was discharged from the hospital without sequelae. Herpes simplex virus (HSV) type 1 was detected from cells in CSF on admission by fluorescence antibody method. HSV antibody titers in sera changed from 1/8 to 1/64 during three months by complement fixation test. Specific IgG and IgA by enzyme linked immunosorbent assay (ELISA) was high in CSF. Specific antibody in CSF/total antibody in CSF: specific antibody in serum/total antibody in serum for IgG and IgA classes were more than 1. Reports of mild type of HSV brain stem encephalitis seemed to be rare. Our case which was followed for several months carefully would be important to discuss.

Antibodies, Viral↗

Dystrophic axons in the nucleus gracilis of the normal rat containing cholecystokinin-like immunoreactivity. Light- and electron-microscopic observations.

Cholecystokinin immunoreactive (CCKI) axons in the nucleus gracilis of the normal rat were studied by light and electron microscopy using the peroxidase-antiperoxidase (PAP) immunocytochemical method. Immunoreactivity was found in both normal and dystrophic axons at various ages. Slightly enlarged CCKI varicosities were first observed in 2-month-old rats, gradually increased in number (max. at 21 months) and in diameter (up to 20 micron at 21 months), and then decreased (at 27 and 36 months). Dilatated CCKI fibers continuous with dystrophic varicosities also tended to increase proportionally in diameter. The dystrophic CCKI axonal profiles, first identified at the light-microscopic level and then observed under electron microscopy, had consistently characteristic features. In addition, numerous dystrophic nonreactive axonal profiles had morphological features differing from those of dystrophic reactive ones at advanced ages. These findings suggest that CCK may be partly involved in the formation of dystrophic axons in the nucleus gracilis.

Aging↗

Enzyme immunoassay of free thyroxin in dried blood samples on filter paper.

We describe a double-antibody enzyme immunoassay for determination of free thyroxin (FT4) in dried blood samples on filter paper, with use of a T4-beta-D-galactosidase complex. The measurable range of FT4 concentration in two 3-mm blood discs, each of which contained about 2.7 microL of blood, was 1.9 to 93 ng/L, as determined by comparison with concentrations of FT4 in known serum standards. FT4 in blood samples dried on filter paper was stable for at least four weeks when kept dry at -20 degrees C, room temperature, or 37 degrees C. The mean coefficients of variation were 7.6% (within assay) and 6.4% (between assays). Results for FT4 by this method correlated well with those for serum determined by radioimmunoassay (r = 0.98). The proposed method can be used to differentiate persons with hyper- and hypothyroidism from normal subjects and those with abnormal concentrations of thyroxin-binding globulin. The procedure seems suited for screening studies.

Adult↗

HLA-A and -B antigens in Japanese patients with congenital hypothyroidism and their parents.

The frequency of HLA-A and B antigens were studied in 32 Japanese patients with congenital hypothyroidism due to thyroid dysgenesis, and in their parents. The incidence of the Aw24 antigen was significantly higher in 27 mothers of patients with ectopic thyroid (91.3%, corrected P less than 0.037) and it seemed to be slightly higher in patients (77.7%) than in controls (56.8%). The Aw24 antigen was also found in 4 patients with thyroid hypoplasia and their mothers. No difference was found in the incidences of the antigen in the fathers of patients and in controls. The haplotype frequencies were not significantly different in controls, patients and their parents. These findings suggest that the gene for susceptibility to congenital hypothyroidism due to thyroid dysgenesis is closely linked to the gene for the HLA-A locus of the patients' mothers.

Adolescent↗

Semiautomated enzyme immunoassay of thyrotropin as a mass screening test for neonatal hypothyroidism.

A sensitive, simple, and rapid semiautomated sandwich enzyme immunoassay (EIA) was developed for measuring thyrotropin in dried blood samples on filter paper for use in screening for neonatal hypothyroidism. Good correlation was found between values for thyrotropin determined by this method and those determined by radioimmunoassay (RIA) (r=0.94). In pilot tests on 17,160 newborn infants in the general population, five cases of primary hypothyroidism were detected by both EIA and RIA. The recall rate was slightly highter in EIA than in RIA.

Autoanalysis↗

Enzyme immunoassay of free thyroxin in serum.

We describe a double-antibody enzyme immunoassay for free thyroxin (FT4) in serum with use of beta-D-galactosidase conjugated to thyroxin. The method is uninfluenced by thyroxin-binding globulin or albumin. Values for FT4 so determined correlated well with those determined by radioimmunoassay (r = 0.98) and equilibrium dialysis (r = 0.89). The mean variability (CV) within and between assays was 7.4% and 7.6%, respectively. The measurable range of FT4 in serum was 2.8 to 109 ng/L. The FT4 concentrations in serum as determined by this method were 8.4 to 15.5 ng/L for 26 normal adult subjects; 26 to greater than 109 ng/L for 10 patients with hyperthyroidism; less than 2.8 to 8.0 ng/L for seven patients with hypothyroidism; 7.3 to 15.8 ng/L for eight pregnant women; and 12.2 and 13.5 ng/L for two patients with low concentrations of thyroxin-binding globulin.

Adult↗

Nuclear magnetic resonance studies on experimental malignant bone tumors.

The relaxation times of water protons were studied by nuclear magnetic resonance (NMR) method in two kinds of experimental malignant bone tumors, intramedullary transplanted VX2 carcinoma and Gardner osteosarcoma 519. The relaxation times for malignant tumor tissues were significantly elevated than those for normal bone tissues. Bone marrow sample, where VX2 carcinoma was transplanted 1 week before and included only a few scattered malignant tumor cells, showed the elevation in the relaxation times compared with that of normal bone marrow. In addition, analyses of the electrolytes and the water content of each tissue suggest that the elevation of the relaxation times is not necessarily attributable to the factor of the water content.

Animals↗