Characterization of equine cytochrome P450: role of CYP3A in the metabolism of diazepam.

Research on drug metabolism and pharmacokinetics in large animal species including the horse is scarce because of the challenges in conducting in vivo studies. The metabolic reactions catalyzed by cytochrome P450s (CYPs) are central to drug pharmacokinetics. This study elucidated the characteristics of equine CYPs using diazepam (DZP) as a model compound as this drug is widely used as an anesthetic and sedative in horses, and is principally metabolized by CYPs. Diazepam metabolic activities were measured in vitro using horse and rat liver microsomes to clarify the species differences in enzyme kinetic parameters of each metabolite (temazepam [TMZ], nordiazepam [NDZ], p-hydroxydiazepam [p-OH-DZP], and oxazepam [OXZ]). In both species microsomes, TMZ was the major metabolite, but the formation rate of p-OH-DZP was significantly less in the horse. Inhibition assays with a CYP-specific inhibitors and antibody suggested that CYP3A was the main enzyme responsible for DZP metabolism in horse. Four recombinant equine CYP3A isoforms expressed in Cos-7 cells showed that CYP3A96, CYP3A94, and CYP3A89 were important for TMZ formation, whereas CYP3A97 exhibited more limited activity. Phylogenetic analysis suggested diversification of CYP3As in each mammalian order. Further study is needed to elucidate functional characteristics of each equine CYP3A isoform for effective use of diazepam in horses.

A method for evaluating the entrance surface dose from the measurement of exposure and half value layer in intraoral radiography using a radiophotoluminescent dosemeter.

A method for measuring entrance surface dose in intraoral radiography for nationwide survey for the determination of guidance levels was developed using a commercially available radiophotoluminescent dosemeter (RPLD) system. From the ratio of the readings of the RPLD detectors. with and without a 1 mm thick aluminium filter, half value layer (HVL) and the energy dependency correction factor were derived. HVL and exposure for intraoral radiography were obtained with uncertainties of +/- 0.11 mmAl (SD) and +/- 2.1% (CV), respectively. This has been achieved by calibration at various beam qualities used in intraoral radiography. The HVLs and outputs of intraoral radiography units were measured by means of the mailed RPLD holders and also by ionisation chambers in 19 dental schools in Japan. Results obtained from the two methods of measurement agreed well for both HVLs and outputs.

Reductions in recruitment force thresholds in human single motor units by successive voluntary contractions.

Recruitment force thresholds of biceps brachii single motor units were studied in 4 male subjects before and after an isometric muscle contraction, passive muscle stretch, or following successive muscle contractions, muscle stretches or during alternations between muscle stretches and muscle contractions. Isometric muscle contractions of 5 s duration decreased subsequent single motor unit force thresholds. These force thresholds could usually be reset at or near precontraction force threshold values by passive muscle stretch induced by elbow extension. Single motor units showing reduced force thresholds following contraction were momentarily derecruited during and/or after muscle stretch. Successive muscle stretches alone did not significantly alter single motor unit force thresholds. In contrast, single motor unit recruitment force thresholds during successive weaker contractions were progressively lowered. Intercontraction muscle stretches maintained the single motor unit force thresholds at or near the initial force threshold level. The mechanism(s) underlying a muscle contraction-induced lowering of single motor unit force thresholds may reside in stretch reflex pathways.

[Anesthesia for patients receiving hemodialysis--a report of 122 cases].

A hundred and twenty-two cases of anesthesia for patients receiving hemo-dialysis were reported and peri-operative management of them was analyzed, retrospectively. For the past ten years, most of the patients were anesthetized with neurolept-anesthesia and post-operative mechanical ventilation was continued until the patients regained stable hemodynamics and complete awareness. The procedures of pre-operative hemo-dialysis and intraoperative management were almost compatible with previous reports. In the cases of emergency operation, pre-operative control was not enough and intra-operative water intake was larger than that of scheduled cases. The detailed analysis of peri-operative management of water which affects the pathophysiological state of each patient will be the problem in future.

[Anesthesia in patients undergoing valvular replacement and coronary artery bypass grafting].

We investigated the intraoperative hemodynamic changes in patients who underwent combined valvular replacement (VR) and coronary artery bypass grafting (CABG). The data of 8 patients who under went VR + CABG were compared with those of 50 patients who underwent VR during the same period (1986). Heart rate before the institution of cardiopulmonary bypass (CPB) was not different between these two group, but blood pressure of VR + CABG cases was significantly higher than that of VR cases. This required a higher dosage of fentanyl in VR + CABG cases.

[Accuracy of the dose distribution].

The purpose of physical treatment planning is to deliver the absorbed dose to the target volume within +/- 5% of the prescribed dose. The greatest accuracy is required for the target volume adjacent to the critical tissues. Accuracy of the dose distribution in the patient is affected by the calculation errors of the dose and the set-up errors of the patient for daily treatments. In order to reduce the errors, quality assurance programme shall be carried out. Quality assurance programmes include acceptance tests and periodic performance tests of the dosimeter, the treatment unit and accessories. The importance of the calibration system of ionization chamber, computerized set-up system and quality assurance programmes is emphasized.

The integral dose in panoramic intraoral x-ray tube radiography.

A Monte Carlo computer program was developed to estimate the integral dose to the head and thyroid for panoramic intraoral x-ray tube radiography. The advantage of this computer simulation is that it is able to avoid many of the difficulties associated with low-energy and low-dose x-ray dosimetry. The calculations were made for maxillary and mandibular projections separately, using 10 kv. increments between 40 and 60 kv. The results obtained were presented in terms of the integral dose per milliampere second. Typical integral doses for a routine examination of the head are 2.1 mJ. and 8.5 microJ for the thyroid during mandibular radiography and 1.7 microJ for the thyroid during radiography of the maxilla using 55 kv. and 0.5 mAs.

[The demography of Japan during the Tokugawa period]. / La demographie du Japon a l'epoque des Tokugawa

PIP: A review of available population data for Japan in the Tokugawa period, which lasted from the seventeenth to the nineteenth century, is presented. The work being done in the area of family reconstitution studies at Tokyo University using these data is discussed. (summary in ENG)^ieng

Class differences in marriage and fertility among Tokugawa villagers in Mino province.

"This paper uses family reconstitution to derive indices of marriage and birth rates from observation of class differences in six villages on the Nobi plain (near Nagoya), [Japan]." The study covers the Tokugawa period, which lasted from 1603 to 1868.