Possible involvement of organic anion transporter 2 on the interaction of theophylline with erythromycin in the human liver.

Organic anion transporter 2 (Oat2 [SLC22A7]) is a multispecific organic anion transporter. Although several substrates of human Oat2 (hOat2) have been elucidated, a possible involvement of hOat2 in drug interaction is less defined. The purpose of this study was to investigate the interaction of theophylline with erythromycin mediated by hOat2 using a Xenopus laevis oocyte expression system. When expressed in Xenopus oocytes, hOat2 mediated the transport of theophylline and erythromycin. The finding indicates that the two compounds are novel substrates for hOat2. The apparent K(m) values for the uptake of hOat2 that mediated the transport of theophylline and erythromycin were 12.6 muM and 18.5 muM, respectively. The hOat2-mediated uptake of [(14)C]theophylline and [(14)C]erythromycin was cis-inhibited by adding erythromycin and theophylline, respectively. Our present findings suggest that hOat2 may, at least in part, be involved in the theophylline-erythromycin interaction in the human liver.     

Studies on the metabolic fate of 14C-rokitamycin. III. Transmigration to fetus or milk

Transmigration of 14C-radioactivity to fetus or milk were studied in 17-18 day-pregnant rats and mother rats on the 14th day after parturition after a single oral administration of 14C-rokitamycin (TMS-19-Q) at a dose of 200 mg/kg. The blood concentration of the drug in the mother reached a maximum level of 22.8 micrograms/ml at 2 hours after administration. Maximum concentrations of TMS-19-Q in placenta, ovary and uterus were attained in 2 hours, and were 28.9, 26.0 and 26.2 micrograms/g, respectively. The distribution to these tissues were considered good. The maximum concentration of TMS-19-Q in the amniotic fluid was attained in 2 hours, at a level of 5.4 micrograms/ml. The transmigration to the amniotic fluid was considered poor. The maximum concentration of the drug in the fetus was achieved in 2 hours at a level of 13.7 micrograms/g. Maximum concentrations of the drug in fetal liver and brain were attained in 4 hours, and were 32.8 and 11.4 micrograms/g, respectively. Whole body autoradiography was done when the radioactivity in maternal blood reached peak concentration. It was found that radioactivities in placenta and fetal membrane were similar to the radioactivity in maternal blood, while the radioactivity in fetal brain was considerably lower than that in maternal blood. Maximum concentrations were found at 1 hour in the blood and at 4 hours in the milk, and were 14.8 and 21.5 micrograms/ml, respectively. Transmigration to the milk was good.     

Thyroplasty Type I with Ceramic Shim

Abstract: To prevent side effects from a silicone shim in Isshiki thyroplasty type I, we used a ceramic shim in 10 patients with unilateral recurrent laryngeal nerve paralysis. No published reports have described the use of ceramic in this type of surgery. According to the degree of glottic insufficiency, ceramic shims of various heights were inserted into the fenestration made in the thyroid ala. All patients experienced subjective improvement of voice postoperatively. Laryngoscopies in most cases showed that glottic insufficiency improved postoperatively. In the postoperative examination, the maximum phonation time improved an average of 3.7 s, and the mean flow rate improved an average of 331 ml/s. We have analyzed the relationship of these improvements to the degree of glottic insufficiency and have compared our results with those of other investigators.     

Measurement of airway resistance in anesthetized and paralyzed subjects: Proposal for evaluation of K1 values

The effects of lung volume and respiratory airflow on airway resistance were studied in five anesthetized and paralyzed patients. Airway resistance measured during the inspiratory phase with intermittent constant airflow inflatoins decreased in inverse correlationship to increases in lung volume. Airway resistance measured during the expiratory phase with an airway interruption technique, on the other hand, increased with a linear relationship to the expiratory airflow as expressed by a function of Y = K₁ + K₂X. K₁, calculated from the values of airway resistance corresponding to three different airflows, was unaffected by intentional expiratory resistance loading. Thus, simultaneously with the measurement of airway resistance by this method, expiratory gas sampling with a Douglas bag can be done if necessary. Since the K₂ value of the endotracheal tube used in this study (Portex^® I.D. 8mm, length 26cm) was quite high (5.0cmH₂O·1^–2·sec²), depending on the airflow, the presence of the endotracheal tube strongly affected the measurement of airway resistance during general anesthesia. K₁ measured by the above method, however, may be considered as the best way to evaluate the lower airway resistance independent of either lung volume or expiratory airflow.(Sakai T, Yoshida H, Yano H et al.: Measurement of airway resistance in anesthetized and paralyzed subjects: proposal for evaluation of K₁ values. J Anesth 2: 139–145, 1988)     

Studies on the enhanced effect of acupuncture analgesia and acupuncture anesthesia by D-phenylalanine (first report)--effect on pain threshold and inhibition by naloxone

It has been claimed that the mechanism of acupuncture analgesia can be explained in part by endogenous opioids. If so, it might be possible to enhance the analgesic effect of acupuncture by the administration of endorphins. If D-phenylalanine (DPA), an inhibitor of the endorphin degrading enzyme, is administered, the analgesic effect of acupuncture should be prolonged due to the increased level of endorphins. From the changes of the pain threshold (PT), we investigated whether or not the pre-administration of DPA can enhance the analgesic effect of acupuncture in humans. In addition, we examined the inhibitory effect of naloxone. 1) In all five subjects whose PT was raised after acupuncture anesthesia (respondents), the rise in PT was significantly prolonged by DPA. 2) Out of 10 subjects whose PT remained almost unchanged after acupuncture anesthesia (non-respondents), the PT was increased by DPA in 5 cases. 3) The rise in PT was most prominent when DPA was administered 30 minutes before the start of acupuncture anesthesia. 4) In all 4 respondents in whom the rise in PT persisted after DPA and acupuncture anesthesia, their raised PT dropped after the intravenous injection of naloxone (10 mg). 5) These findings show that DPA enhances the analgesic effect of acupuncture by the "endorphin mechanism."     

"My hand" sign associated with tactile extinction in two patients with callosal lesion

Two patients with "my hand" sign in association with tactile extinction from callosal lesion, one due to left anterior cerebral artery occlusion, the other due to right anterior cerebral artery aneurysm rupture, were reported. The examination of "my hand" sign was performed with the methods proposed by Brion et al. Our patients correctly responded when they grasped their own or the examiner's thumb with their left hand. But they replied "my finger"when they grasped not only their own but also the examiner's thumb with their right hand. Left tactile extinction was observed after a routine extinction test in one patient, and it was observed in the other after the following method: both patient's index fingers were disposed in his midline position. In these methods of extinction test, they made errors in saying "right" when both fingers were touched simultaneously. However, they said "both" when their right index finger alone was touched (synchiria) during an extinction test using the following method: both index fingers of patients were approached by examiner to touch each other or for one of them to touch the examiner's finger. When they were asked whose finger they touched in this method (whose finger test), they made the same errors as seen in "my hand" sign test. These test results suggest that there is a common underlying mechanism in the "my hand" sign and extinction, because the sense of double stimulations felt when only one stimulation is given (synchiria), is a possible explanation for the "my hand" sign and the pathogenesis of synchiria appears to be related to extinction.(ABSTRACT TRUNCATED AT 250 WORDS)