[Comparison of circadian variation of serum theophylline concentration and bioavailability between Theo-dur tablet and a new sustained-release theophylline formulation (E-0686 granule)].
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Biomedical subjects
Publications and source records attributed to T Uekusa.
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To date, no reliable report on the regeneration of the intrahepatic bile duct epithelium following damage to the duct has been published. In this study, a direct instillation of paraquat dichloride into the intrahepatic bile ducts of rats was carried out, and the livers were examined under light and electron microscopy. One hour after treatment, the biliary epithelia showed degeneration and necrosis, and these changes remained for a considerable period in a large majority of the ducts examined. Three weeks after instillation, low columnar epithelium consisting of hyperchromatic nuclei and eosinophilic cytoplasm was present in a medium-sized bile duct, which was collared by marked periductal fibrosis. Electron microscopically, the eosinophilic epithelium showed a marked increase in the number of rough endoplasmic reticula, ribosomes, mitochondria, and filamentous structures, suggesting an active viability of the cell. Subsequently, the eosinophilic cells were replaced by normal-appearing epithelium, not associated with the periductal fibrosis. The data suggest that an epithelial regeneration occurred in the intrahepatic duct following injury and that this activity may be similar to that of the extrahepatic bile duct epithelium.
Fundamental and clinical evaluation on ceftriaxone (Ro 13-9904, CTRX) was performed. CTRX was compared with CEZ, CMZ, CTX and LMOX in the antibacterial activity against the clinical isolates such as S. aureus, E. coli, P. mirabilis, K. pneumoniae and S. marcescens. Against S. aureus, the MIC of CTRX ranged from 0.2 to greater than 100 micrograms/ml with a peak of 3.13 micrograms/ml, showing that CTRX was almost equal to CTX in activity, slightly superior to LMOX and much inferior to CMZ and CEZ, although some strains were not susceptible to CEZ. Against the intestinal strains of E. coli, K. pneumoniae and P. mirabilis, the MIC distribution of CTRX was similar to that of CTX and LMOX while CTRX showed the MIC as high as 3.13 micrograms/ml or above against 44% of all strains including the beta-lactamase producing strains of E. coli and K. pneumoniae, indicating a slight tendency of their becoming resistant. The MIC peaks against E. coli, K. pneumoniae and P. mirabilis were less than or equal to 0.1, 0.39 and less than or equal to 0.1 microgram/ml, respectively. As to S. marcescens which is drawing attention as a causative agent for infections inside of hospitals or those among young infants, CTRX inhibited 84% of the strains at 3.13 micrograms/ml, showing a definite superiority to CEZ and CMZ and a slight superiority to CTX and LMOX. The serum concentration after a single intravenous injection with 40 mg/kg reached a mean peak of 168.8 micrograms/ml at the first blood sampling (at 30 minutes) and gradually decreased to 137.5 micrograms/ml at 1 hour, 30.9 micrograms/ml at 6 hours, 12.6 micrograms/ml at 12 hours and 3.8 micrograms/ml at 24 hours, while the half-life time was 6.0 hours. The comparison of the serum level by 1 hour intravenous drip infusion between the dosage groups of 20 mg/kg and 40 mg/kg revealed that the former group reached a peak of 85.4 micrograms/ml at the termination of drip while the latter's peak was 176.6 micrograms/ml observed during the drip (30 minutes after the initiation of drip). The respective levels of the 2 groups were 15.4 and 32.1 micrograms/ml at 6 hours, 5.1 and 15.0 micrograms/ml at 12 hours, and 1.6 and 4.1 micrograms/ml at 24 hours, indicating a distinct dose-response 2 hours after the initiation of drip administration. The half-life times were 4.9 and 6.2 hours, respectively, which are the longest among the cephalosporins presently being developed.(ABSTRACT TRUNCATED AT 400 WORDS)
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Five children with allergic rhinitis sensitive to house dust mite as documented by skin test, radioallergosorbent test, score and nasal provocation were studied. Patients were subjected to nasal challenge with 3.125, 6.25, 12.5, and 25 protein nitrogen micrograms per disc of house dust mite antigens and nasal secretions were collected by the filter paper method. Neutrophil chemotactic activity (NCA) and histamine content of the nasal secretions were measured. NCA and histamine were released in a dose- and time-dependent manner, and no significant correlation between NCA and histamine was revealed in each subject. Pretreatment with 5.2 mg of nasal disodium cromoglycate or 0.5 micrograms of nasal adrenaline 5 minutes before provocation totally inhibited mediator release upon nasal challenge with 12.5 micrograms of house dust mite. A dose of 100 micrograms of nasal beclomethasone dipropionate 5 minutes before challenge neither inhibited clinical symptoms nor mediator release; 100 micrograms x 3 times per day of nasal beclomethasone dipropionate for 3 days, however, significantly inhibited clinical symptoms and release of both NCA (p less than 0.05) and histamine (p less than 0.05). NCA eluted as a single peak with an estimated molecular weight of 600,000. These results suggest that high molecular weight-NCA may be involved in the pathogenesis of allergic rhinitis.