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S Ohdo

Publications and source records attributed to S Ohdo.

At least 55 records · Page 3Linked to original sources
PubMed1995

Chronopharmacological study of acetylsalicylic acid in mice.

Influence of dosing time on pharmacological effects and toxicity of acetylsalicylic acid was investigated in ICR male mice under light-dark (12:12) cycle. Significant circadian rhythms (day-night rhythms) were demonstrated for hypothermal and analgesic effects at 1 h after an injection of acetylsalicylic acid (200 mg/kg, i.p.) (P < 0.01, respectively). The rhythmic patterns of acetylsalicylic acid induced analgesia and hypothermia resembled overall the rhythms occurring in the non-drugged state. Injection of acetylsalicylic acid resulted in a parallel increase in latency to hot plate and a parallel decrease in rectal temperature. The relationship between plasma salicylate concentrations and responses was not clear. There was also a significant circadian rhythm in acetylsalicylic acid (850 mg/kg, i.p.) induced toxicity with the highest mortality at 17:00 and the lowest one at 05:00 (P < 0.05). Dosing time dependent kinetics of salicylate seems to be related to the rhythm of toxicity of the drug. The time in circadian stage at which acetylsalicylic acid is administered is essentially important in the actions of acetylsalicylic acid.

Analgesics↗
PubMed1995

Alteration in circadian rhythm of plasma corticosterone in rats following sociopsychological stress induced by communication box.

The purpose of present study was to investigate the physiological characteristics of sociopsychological stress induced by the communication box method. In this method, the nonfoot shocked rats were used as the psychological stressed experimental group. The stress exposure was loaded for 1 h between 0900 and 1000, daily. The changes in circadian rhythm of plasma corticosterone were studied following the 3-day, 5-day, or 10-day stress exposure, respectively. Plasma corticosterone levels of foot shocked rats and nonfoot shocked rats following the 3-day or 5-day stress exposure were significantly higher than those of control rats. Particularly, the marked elevation of plasma corticosterone was observed at the peak time of circadian rhythm (2100) in the both stress groups. Consequently, the amplitude of 24 h rhythm increased significantly, but the acrophase was not changed. However, the changes of plasma corticosterone levels of both stress groups following the 10-day stress exposure approached those of control group. These results suggest that the repeated exposure of sociopsychological stress can influence the circadian rhythm of plasma corticosterone. The communication box method may be a valuable tool for researching the etiology of human psychiatric disorders with rhythm disturbance.

Animals↗
PubMed1995

Manipulation of the lighting schedule can modify the pharmacological effects of theophylline in chick embryos.

The effect of the lighting schedule on the pharmacological action of theophylline was studied in chick embryos. Fertile eggs of White Leghorns were incubated and investigated, on two occasions, under constant light conditions or under constant dark conditions. A single injection of theophylline 2.14, 4.29, 8.57 and 17.14 mg/egg into the air sac of fertile eggs was carried out on the 16th day of incubation. Electrocardiograms (ECGs) were recorded 0 to 60 min after drug injection. After drug injection, heart rate increased under constant light conditions, but decreased under dark conditions. In addition, arrhythmia was produced by theophylline, 17.14 mg/egg, under constant dark conditions. These results indicate that the manipulation of the lighting schedule may have a marked influence on the pharmacological effects of theophylline in chick embryos.

Animals↗
PubMed1995

Chronopharmacokinetics of valproic acid following constant-rate administration in mice and influence of feeding schedule.

AIM: To study the circadian rhythm in pharmacokinetics of valproic acid (VA) and influence of feeding schedule on the rhythm. METHODS: Sodium valproate was administered by osmotic minipump technique (1.062 mg.h-1) and i.v. (50 mg.kg-1) to ICR mice fed under ad lib or time-restricted schedules to determine the time-dependent changes of VA kinetics. RESULTS: Plasma VA concentration and clearance at steady-state showed circadian rhythms (P < 0.01). Time-restricted feeding influenced the rhythm of VA kinetics, acrophases of rhythms shifted approximately 12 h. CONCLUSION: Timing of dosing is important for VA kinetics and feeding schedule is one of synchronizers in VA kinetics.

Animals↗
PubMed1995

[Lithium carbonate].

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Antidepressive Agents↗
PubMed1994

[The normal body temperature lowering effect of aspirin in mice and its circadian rhythm].

It is generally believed that the effectiveness of salicylates, such as aspirin (ASP), is restricted to the lowering of the body temperature (BT) previously elevated by pyrogens and that salicylates have no effect on normal BT. We present here evidences which demonstrate that ASP does lower the normal BT of mice kept in a 24 degrees C environment. Male ICR mice, housed under a light-dark cycle (LD 12:12h) at a room temperature of 24 +/- 1 degree C and a humidity of 60 +/- 10% with food and water ad libitum, received intraperitoneal injections of ASP 25, 100 and 200 mg.kg-1. The animals showed a significant decline in their rectal temperature and the BT returned to the values that prevailed before drug administration within 4 h. There was an orderly, progressive dose-dependent decrease in BT. A significant circadian rhythm was demonstrated for ASP-induced hypothermal effect in mice. Although a significant circadian rhythm was also demonstrated for the plasma salicylate concentrations at 1 h after dosing, there seems to be no positive relationship between plasma drug concentrations and the drug response. The results suggest that ASP does affect normal BT regulation in mice and that the circadian rhythm change in ASP-induced hypothermal effect may be mainly due to the rhythms in the sensitivity of mice to the drug.

Animals↗
PubMed1993

Sodium valproate-induced cardiovascular abnormalities in the Jcl:ICR mouse fetus: peak sensitivity of gestational day and dose-dependent effect.

Sodium valproate was administered to Jcl:ICR mice in order to determine its effect on cardiovascular development. A single dose of 600 mg/kg of sodium valproate was injected intraperitoneally on gestational days 6, 7, 8, or 9. In same animals, a single dose of 300, 400, 500, or 700 mg/kg was injected on gestational day 7. On day 18 of gestation, dams were laparotomized to observe number of live, dead and resorbed fetuses. In addition, live fetuses were examined for cardiovascular abnormalities. Although cardiovascular abnormalities were noted in 3% of live fetuses and in 26% of litters in the group treated on day 6 (600 mg/kg), there was no significant difference from the control group, suggests that there may have been a biologically significant increase, although not a statistically significant increase. Cardiovascular abnormalities were found in 30%, 11%, and 8% of live fetuses in the groups treated with 600 mg/kg on days 7, 8, and 9, respectively. These represented a statistically significant increase in effects as opposed to the control groups. Among the varying dosages administered on day 7 of gestation, cardiovascular abnormalities occurred in 2%, 6%, 16%, and 36% of live fetuses in groups treated with 300, 400, 500, and 700 mg/kg, respectively, showing a significant dose-dependent increase. These cardiovascular abnormalities observed were divided into the following groups: ventricular septal defect, endocardial cushion defect, transposition of the great arteries, double outlet right ventricle, tricuspid atresia, and hypoplastic left heart syndrome. Maternal death did not occur at any treatment level.

Animals↗
PubMed1993

Chronotoxicity and chronopharmacokinetics of methotrexate in mice: modification by feeding schedule.

The circadian rhythms of the toxicity and the pharmacokinetics of methotrexate (MTX), as well as the effects of manipulation of feeding schedule on the rhythms, were investigated in mice. Male ICR mice were housed under a standardized light-dark cycle (12:12) with food and water ad libitum (ALF) or under the time-restricted feeding (TRF) schedule (8 hr during the light phase) for 1 day or 14 days before the drug administration. The animals received MTX (100 mg/kg, i.p.) once daily for 7 days in the toxicity studies and a single dose of MTX (100 mg/kg, i.p.) for the kinetic studies. Under the ALF, a significant dosing time dependency was demonstrated for the toxicity of MTX with a longer survival time for the middark dosing and a shorter one for the midlight dosing. The MTX kinetics also showed a significant rhythm, with the highest clearance at middark and the lowest one at midlight. The rhythm in MTX kinetics well coincided with that in the toxicity of the drug. The TRF had a marked influence on the rhythms of MTX kinetics and toxicity. Thus, the timing of dosing is important in the kinetics and the toxicity of MTX in mice, and the manipulation of feeding schedule can modify the rhythm of the toxicity by changing that of the MTX kinetics.

Animals↗
PubMed1993

Influence of feeding schedule on chronopharmacological aspects of gentamicin in mice.

The effects of the time of day of drug administration on the subchronic toxicity and pharmacokinetics of gentamicin, as well as the role of feeding schedule on circadian rhythms, were investigated in mice. ICR male mice were housed in a light-dark (LD) cycle (12:12) with food and water ad libitum (ALF) or under a time-restricted feeding (TRF) schedule (feeding time: 8 h during the light phase) for 1 day or 14 days before drug administration. The animals were given a single subcutaneous dose of gentamicin 180 mg/kg for the kinetic studies and subcutaneous doses of gentamicin 180 mg/kg/day for 14 days or 220 mg/kg/day for 18 days for the subchronic toxicity studies. A significant dosing-time dependency was shown for mortality and body weight loss, with higher values at midlight and lower ones at the middark (p < 0.05). A significant circadian rhythm was also found for gentamicin kinetics in ALF mice, with the highest clearance at middark and the lowest one at midlight (p < 0.01). The kinetic rhythm of gentamicin coincided well with the toxicity rhythm of the drug. The TRF schedule had a marked influence on the rhythms of gentamicin kinetics and toxicity, showing lowest clearance and higher toxicity at middark. The rhythm of subchronic toxicity of gentamicin seems to be due, at least in part, to the rhythm in kinetics and is strongly influenced by the feeding schedule. Thus, the timing of dosing is an important factor in the kinetics and the subchronic toxicity of gentamicin administration in mice, and the manipulation of feeding schedule can modify the rhythm of the toxicity by changing the rhythm of gentamicin kinetics.

Animals↗
PubMed1993

[Chronopharmacology and DDS (drug delivery system)].

Rhythmic variations, including circadian and circannual ones, have been demonstrated in the pharmacokinetics and pharmacodynamics of many drugs. These suggest that the consideration of the timing of drug administration will improve rational drug therapy, increasing drug efficacy and safety. A drug delivery system (DDS) enabling a constant-rate administration is attractive from the clinical point of view, namely, such a system could minimize the peak and trough variation in plasma drug concentration after dosing so as to avoid toxicity associated with drug levels exceeding the upper limit of therapeutic range and lack of effect with drug levels dropping below the lower limit of the range. However, pulsatile administration is preferred for peptide and hormone pharmacotherapy. For chronopharmacotherapy, a pattern of input at different release rates is also preferred to that at a constant rate. These findings emphasize the need to consider chronopharmacology in DDS design.

Adult↗
PubMed1992

Circadian changes of valproate kinetics depending on meal condition in humans.

The objective of this study was to examine the effect of meal condition on circadian changes in valproic acid (VPA) kinetics. Two experiments were performed in 16 healthy men that were synchronized with diurnal activity and nocturnal rest as their routine life. In both experiments, four 200-mg tablets of VPA were given orally on two occasions in the morning (8:30 AM) or in the evening (8:30 PM). In each study, a randomized, single-dose, two-way crossover design was used, and 2 weeks elapsed between morning and evening trials. In experiment 1, eight subjects took a light meal as breakfast between 8:00 and 8:15 AM and a heavy meal as dinner between 6:00 and 6:30 PM to fit the subject's usual food amount. The mean peak plasma concentration (Cmax) was significantly higher (P less than .01), the time to peak concentration (tmax) was shorter (P less than .05), and the absorption rate (Ka) was larger (P less than .05) after the morning dose than after the evening dose. In experiment 2, the size and contents of meal in breakfast and dinner were prepared in the same manner as the standard breakfast for the subjects. Namely, eight subjects took the same light meal between 8:00 and 8:15 AM in the morning and between 8:00 and 8:15 PM in the evening. There was no significant circadian change in VPA kinetics under this same meal condition. These results suggest that the differences of meal condition between morning and evening in our daily life play a major role in the mechanism underlying the circadian changes of VPA absorption in man.

Absorption↗
PubMed1992

Cardiovascular anomalies in chick embryos produced by bis-diamine in dimethylsulfoxide.

N,N'-bis(dichloroacetyl)-1,8-octamethylenediamine(bis-diamin e) (100 micrograms) dissolved in dimethylsulfoxide (DMSO) was administered to early developing chick embryos (Hamburger-Hamilton stage 9-21) in order to clarify the teratogenic effects on the cardiovascular system and to determine whether bis-diamine interferes with the migration of neural crest cells. Of 346 cases, 154 (44.5%) survived. The incidence of cardiovascular anomalies was 149 out of 154 cases (96.8%). Infundibular ventricular septal defect, double outlet right ventricle, and persistent truncus arteriosus were the primary cardiac anomalies observed in this study. A high percentage of these anomalies were accompanied by hypoplasia of the right 6th aortic arch artery and persistent left 4th aortic arch artery. Particularly, administration of bis-diamine to chick embryos at stage 13 resulted in a high incidence of persistent truncus arteriosus (64.3%). Bis-diamine has been suspected to inhibiting the migration of neural crest cells. However, neural crest cells were observed in the tunica media of the great arteries and the truncal valves of persistent truncus arteriosus produced by bis-diamine in chimeric embryos at stage 13. Morphological changes such as cell death were not observed.

Abnormalities, Drug-Induced↗
PubMed1992

Light-dark variations in ocular timolol concentrations following topical solution instillation in the pigmented rabbit.

The objective of this study was to determine whether ocular absorption of topically applied timolol in the pigmented rabbit varied with the time of drop instillation. Twenty-five microliters of a 0.65% timolol maleate solution were instilled in the pigmented rabbit eye at 0600, 0900, 1200, 1500, 1800, 2100, 2400, or 0300 hr. Timolol concentrations in the conjunctiva, sclera, corneal epithelium, corneal stroma, aqueous humor, and iris-ciliary body at 15 and 30 min post-dosing were monitored using reversed phase HPLC. Ocular timolol concentrations were higher when the drug was administered during the light period (0900-1800 hr) than when it was administered during the dark period (1800-0600 hr). There exist, therefore, light-dark variations in the ocular absorption of topically applied timolol.

Absorption↗
PubMed1992

Plasma corticosterone response of rats with sociopsychological stress in the communication box.

The purpose of present study was to investigate the physiological characteristics of sociopsychological stress induced by the communication box method. In this method, the nonfoot shocked rats were used as the psychologically stressed experimental group. In acute stress experiments, nonfoot shocked rats were exposed to emotional responses from foot shocked rats for 6 h in the light (0900-1500) or in the dark phase (2100-0300). In the light phase, the induced increase in plasma corticosterone levels of nonfoot shocked and foot shocked rats returned to corresponding control levels 6 h following the initiation of stress session, whereas those in the dark phase were significantly higher. Although there were some differences in corticosterone responses between both phases, the acute effect of sociopsychological stress was unclear. Chronic stress experiment with daily exposure for 1 h to sociopsychological stress caused the plasma corticosterone levels of nonfoot shocked rats to increase significantly not only in the postexposure level (just after stress exposure) but also in the preexposure level (before stress exposure) when naive rats were used daily as foot shocked animals. These results suggest that the repeated exposure of sociopsychological stress can induce physiological changes, and stressful situation can be established with only emotional responses from foot shocked rats.

Animals↗
PubMed1992

Etiologic and pathogenetic study of mental retardation with multiple congenital anomalies.

Etiology and pathogenesis of MCA/MR in 1,023 patients (618 male; 405 female) with mental retardation were studied. Of 1,023 patients, there were 563 cases (317 male; 246 female) with MCA (55%). Among the MCA patients, there were 303 (156 male; 147 female) whose primary etiology was clarified (53.8%). Among the 260 patients with MCA/MR of unknown etiology, there were 23 with recognizable syndromes of unknown etiology and 7 previously reported by us as possibly having a new malformation syndrome. We had 569 patients with mental retardation of unknown etiology including 263 (41.5%) who were involved with MCA.

Brain↗