Inhibition of hepatic drug-metabolizing enzymes by thiophosphate insecticides and its drug toxicological implications.
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Biomedical subjects
Publications and source records attributed to K Homma.
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Thiophosphate insecticides, fenitrothion, diazinon and methylparathion, inhibit hepatic drug-metabolizing enzyme activity which was assayed using aminopyrine and aniline as substrates. About 50% inhibition was observed 4 hrs after the injection of fenitrothion into mice in a dose of 25 mg/kg. The addition in vitro of thiophosphates into a reaction mixture of drug metabolizing enzyme also produced an effective inhibition and IC50 was around 10(-5)M for fenitrothion. DDVP and oxygenated metabolite of fenitrothion did not show any inhibiting effect either in vitro or in vivo. The inhibition of thiophosphates in vitro was competitive while the kinetics of in vivo inhibition was shown as non-competitive. The drug metabolism in the rat liver preparation was also inhibited by thiophosphate in vitro, but in vivo treatment to male rats resulted in only slight inhibition. Female rats exhibited the similar response as mice. The administration of fenitrothion to mice prolonged the hexobarbital sleeping time and, consequently, suppressed the oxidative metabolism of parathion in liver preparation. These effects reveal that the biological half life of thiophosphate insecticides could be altered by the mode of administration or by co-existing thiophosphates.
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Because of the long term persistence of free-running circadian rhythms in populations of unicells, several investigators have considered, but not demonstrated, a possible role for intercellular interaction in maintaining synchrony between individual cells. The experiments described here were designed to test more critically the possibility that there is interaction between cells, including those possessing only small phase differences. None was detected; the bioluminescent glow of the mixed cultures matched the algebraic sum of the independent control cultures.
In the first cycle following transfer from a 12 h light-12 h dark cycle (LD12:12) to constant darkness (DD), the standard deviation in circadian phase among individual clocks in populations of Gonyaulax polyedra is approximately 60 min. When a culture is transferred to constant light conditions (LL) from an LD 12:12 cycle, the standard deviation increases in the first 2-3 d, but then remains unchanged, suggesting a lack of observable desynchronization in LL after the transient period. The synchrony in a cell population is preserved even after several cell divisions. The results indicate that variations in period among cells are small, that the period of an individual clock does not fluctuate randomly from day to day, and that the circadian phase of a mother cell is faithfully passed to the clocks of the daughter cells.
Intradermal stitch blepharoplasty is one of the most frequently performed aesthetic surgeries in Japan. The major disadvantage of this method is the general feeling that it is nonpermanent. Mutou and Mutou [1] first published this technique in 1972. From 1957 to 1997, they have performed 20,098 cases of this procedure. The aim of this study was to furnish a retrospective analysis of a failure rate after intradermal double-eyelid operations that had been performed by a single surgeon (Y. Mutou). We evaluated consecutive patients (male 115, female 1,457) from 1986 to 1993 who underwent intradermal blepharoplasty at Sapporo Chuo Keisei Geka Clinic. Fifty patients (male 3, female 47) revisited our clinic complaining of the "disappearance" or loss of the fold. The estimated disappearing rate was 3.43%. Thirty percent of the disappearance occurred within 1 year. Eighty-eight percent of the disappearances occurred within 5 years postoperatively.
Normal skin extensibility in the living body of 94 healthy male subjects ranging in age from 3 months to 73 years was determined quantitatively with the Bio-Skin Tension Meter at 12 sites. In comparison with the age of 20-29 years, the skin extensibility, particularly in the age group of less than 2 years, was significantly high. However, no significant difference from the age groups of 12-14, 15-19, 30-49 and over 50 years was found at any site. Correlation by age was noted at the extremities, excluding the posterior upper arm and at the lower abdomen, with the extensibility of the group less than 1 year as the maximum value, decreasing gradually down to 3-5 or 6-8 years. At the cheek, shoulder, anterior chest, and posterior upper arm, however, no correlation with age was noted.
When duodenal content is allowed to reflux into the esophagus of nitrosamine-treated rats, esophageal cancer is induced more rapidly and at higher frequency than after carcinogen treatment alone. The purpose of the present study was to identify the components of the duodenal content that are responsible for enhancing esophageal carcinogenesis. Eight-week-old Sprague-Dawley rats underwent one of four operations as follows: diversion of bile alone, pancreatic juice alone, both bile and pancreatic juice into the esophagus, or a control operation with no induced reflux. Two weeks after surgery, rats were treated with the esophageal carcinogen 2, 6-dimethylnitrosomorpholine (48 mg/kg [0.1 of LD50] intraperitoneally weekly for 20 weeks). The rats were killed at age 30 weeks. The esophagus was removed and full-length strips were examined under a microscope; separate segments were taken for flow cytometric evaluation. The prevalence of DNA aneuploidy and histologic esophageal papillomas or squamous cancer was increased in carcinogen-treated rats with pancreatic juice reflux (P <0.05 vs. control) and the combination of pancreatic and bile reflux (P <0.05 vs. control) but not in rats with bile reflux alone. We conclude that pancreatic juice is the most potent component of the duodenal refluxate in the promotion of esophageal carcinogenesis in rats.
A novel etching method for an optical fibre probe of a scanning near-field optical microscope (SNOM) was developed to fabricate a variety of tip shapes through dynamic movement during etching. By moving the fibre in two-phase fluids of HF solution and organic solvent, the taper length and angle can be varied according to the movement of the position of the meniscus on the optical fibre. This method produces both long (sharp angle) and short (wide angle) tapered tips compared to tips made with stationary etching processes. A bent-type probe for a SNOM/AFM was fabricated by applying this technique and its throughput efficiency was examined. A wide-angle probe with a 50 degrees angle at the tip showed a throughput efficiency of 3.3 x 10(-4) at a resolution of 100 nm.
We have developed a high-speed scanning near-field optical microscope (SNOM)/atomic force microscope (AFM) system including dual feedback controllers. The system includes an additional piezoelectric actuator with fast response in the z direction and a correction circuit to eliminate unnecessary components from the feedback signal. From the measurement of a patterned chromium layer of 2 x 2 microm2 checks on a quartz glass plate, we confirmed that our system had more effective feedback control and faster scanning than current SNOM/AFM systems that use only a piezo-tube. The scanning speed of the present system was estimated to be about five times faster than that of current SNOM/AFM systems.
The vitrification technique was applied to the preservation of human skin. This technique was simple, and no expensive equipment was needed. Split-thickness human skins from 8 patients were immersed in vitrification solution for 10 minutes at room temperature, immediately plunged into a liquid nitrogen tank, and cryopreserved for 3 weeks. The vitrification solution consisted of 40% ethylene glycol (vol/vol) and phosphate buffered saline solution that contained 30% Ficoll 70 (vol/vol; Wako Junyaku, Co, Tokyo, Japan) and 0.5 mol/L sucrose. The viability of vitrified and cryopreserved skin was evaluated with the trypan blue dye exclusion test, the methyl-thiazoldiphenyl-tetrazolium (MTT) colorimetric assay, and a culture test of the keratinocytes obtained from vitrified skin. The results of the trypan blue dye exclusion test showed 87.4% of viable cells, and MTT developed an average 0.817 absorbance. When vitrified skin was compared with 4 degrees C refrigerated skins after 3 weeks of storage, the difference of viability was significant both on the trypan blue dye exclusion test (P < .05) and on the MTT assay (P < .01). However, there was no significant difference in the viability of vitrified skins compared with fresh skin. Furthermore, keratinocytes from vitrified skin grew uneventfully in culture test. We used these vitrified skin allografts for patients with flame burns and electric burns. These allografts took well in both cases and promoted wound healing. We concluded that the vitrification method for skin preservation is simple and reliable, and this method could contribute to skin banking.