Biological & pharmaceutical bulletin
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The present study was undertaken to elucidate pathophysiological and pharmacological alterations in the right ventricle in monocrotaline-administered (MCT) rats. Examination of tissue weights of the MCT and age-matched control (CON) rats indicated the right ventricular (RV) hypertrophy until 8 weeks after a single subcutaneous administration of 60 mg/kg MCT. Apparent fibrosis in the right ventricle of the MCT rat at the 6th week (6w-MCT) was observed. ⋯ Injection of dobutamine (300 ng) or colforsin daropate (1 microg) into the perfused right ventricle isolated from CON rat at the 6th week resulted in a marked increase in cardiac double product, whereas injection of either agent into the right ventricle from the 6w-MCT rat elicited a small increase in the double product, followed by a sustained decrease in the developed tension. Infusion of acetylcholine (1 microg) into the RV muscle of the 6w-MCT rat resulted in prolongation of the periods for cardiac arrest and for bradycardia of the right ventricle. The results suggest that MCT administration causes the RV hypertrophy and eventually leads to the RV failure, accompanied by abnormal inotropic and chronotropic actions of the RV muscle.
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Randomized Controlled Trial
Effect of a Kampo preparation, byakkokaninjinto, on pharmacokinetics of ciprofloxacin and tetracycline.
The effect on the bioavailability of the antimicrobial agents (ciprofloxacin and tetracycline), which are well known to form chelates with cationic metals such as calcium, was evaluated in 20 healthy male volunteers according to an open, random crossover fashion using a Kampo preparation, byakkokaninjinto (TJ-34) which contains various cationic metals including calcium. Each subject received a single oral dose of tetracycline (250 mg) alone or ciprofloxacin (200 mg) alone along with a single coadministration of one pack (3 g) of the Kampo preparation, at one-week intervals. Concentrations of the drugs in plasma and urine were analyzed by HPLC. ⋯ The Kampo preparation significantly decreased the urinary recovery of tetracycline, but not ciprofloxacin, and it had no effect on the renal clearance of either ciprofloxacin or tetracycline. These results indicate that the Kampo preparation tested in this study reduces the extent of bioavailability of ciprofloxacin and tetracycline, but not renal excretion, by decreasing the gastrointestinal absorption due to the formation of insoluble chelates with calcium. We recommend that the dose timing of the Kampo preparation should be carefully controlled to avoid therapeutic failure especially for patients receiving the treatment with tetracycline.
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micro-Opioid receptor agonists, such as morphine, are widely applied in pain therapy clinical practice. However, the effects exerted by morphine via receptor are influenced by individual specificity. Single nucleotide polymorphisms (SNPs) in micro-opioid receptor gene (OPRM1) have been reported to influence receptor expression and function. ⋯ Moreover, linkage analysis revealed novel linkage between -1748G/A and -172G/T, which was not observed in studies performed in other nations. In contrast, SNPs frequency detected in this study was similar to previously reported results on Asians; however, linkage disequilibrium reports from different nations differed. These results possibly provide useful information for OPRM1 genotyping in the Japanese population.
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We compared the inhibitory action of gabapentin, which is used to treat neuropathic pain, on mechanical allodynia induced by chemotherapeutic agents, paclitaxel, oxaliplatin, and vincristine, in mice. Single injections of paclitaxel, oxaliplatin, and vincristine at the doses corresponding to doses clinically used caused mechanical allodynia of similar intensity. Oral administration of gabapentin (30, 100 mg/kg) produced a dose-dependent inhibition of allodynia caused by paclitaxel and oxaliplatin, but not vincristine. ⋯ Vincristine was without effects on alpha(2)delta-1 subunit mRNA in these regions. These results suggest that the efficacy of gabapentin in the treatment of mechanical allodynia is dependent on chemotherapy agent used. It may be partly due to the distinct effects of chemotherapy agents on the expression of alpha(2)delta-1 subunit of voltage-dependent calcium channel.
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The present study was performed to investigate the effects of histamine H(1)-antagonists on the sleep-awake state in rats placed on a grid suspended over water in comparison with rats placed on sawdust. When rats were placed on the grid suspended over water, significant increases in the awake time and decreases in non-rapid eye movement (non-REM) sleep time were observed compared with in rats on sawdust, even when measured hourly for 6 h. ⋯ Different from these two drugs, promethazine caused a significant decrease in the awake time and increase in non-REM sleep time 1-2 h and 2-3 h after administration even when rats were placed on sawdust at a relatively high dose. These results clearly indicate that histamine H(1)-antagonists had potent effects on decreasing the awake time and increasing non-REM sleep time under the conditions of an activated histaminergic system.