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Dose-response Effects (dose-response + effects)
Selected AbstractsDose-response effects of zaleplon as compared with triazolam (0·25 mg) and placebo in chronic primary insomniaHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 8 2000Christopher L Drake Abstract The effects of two nights of treatment with the short-acting benzodiazepine receptor agonist zaleplon, triazolam, or placebo was assessed in chronic primary insomniacs using two concurrent, multi-center, randomized, double-blind, Latin Square crossover studies. Study 1 (n = 47) compared zaleplon (10 and 40 mg) to triazolam (0·25 mg) and placebo. Study 2 (n = 36) compared zaleplon (20 and 60 mg) to triazolam (0·25 mg) and placebo. For each study, polysomnographically recorded sleep parameters and patient reports of sleep quality were collected during baseline and two consecutive nights during the four treatment phases in each study. All doses of zaleplon produced significant decreases in latency to persistent sleep. Although no minimally effective dose could be determined, dose-response effects were apparent. Triazolam 0·25 mg produced a decrease in latency to persistent sleep that was comparable to that of zaleplon 10 mg. Only the triazolam dose and the 60 mg dose of zaleplon produced significant increases in total sleep time over placebo. Zaleplon 40 and 60 mg and triazolam produced decreases in the percentage of REM sleep compared to placebo. Patient reports of efficacy were consistent with objective findings. In addition, all doses of zaleplon tended to increase while triazolam decreased the percentage of stage 3/4 sleep. There was no evidence of residual daytime impairment for any of the zaleplon doses, however, triazolam administration produced significant impairment in performance on a digit copying test. A higher number of adverse events were seen with the 40 and 60 mg doses of zaleplon compared to triazolam (0·25) and placebo. At higher doses, zaleplon is more effective than triazolam at reducing latency to persistent sleep in chronic insomnia and is not associated with the decrease in slow-wave sleep or residual impairment observed with triazolam. However, increases in total sleep time were apparent only at doses which produced concomitant increases in the number of adverse events. In contrast, triazolam (0·25 mg) produced increases in total sleep time (,25 min) and decreases in latency to persistent sleep at a dose of 0·25 mg. Copyright © 2000 John Wiley & Sons, Ltd. [source] The Dose-Response Effects of Ethanol on the Human Fetal Osteoblastic Cell LineJOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2001A. Maran Abstract Alcohol is a risk factor for the development of osteoporosis, especially in men. Chronic alcohol abuse decreases bone mass, which contributes to the increased incidence of fractures. To better understand the mechanism of action of ethanol on bone metabolism, we have studied the dose-response effects of ethanol on conditionally immortalized human fetal osteoblasts (hFOB) in culture. Ethanol treatment had no significant effects on osteoblast number after 1 day or 7 days. Ethanol treatment did not reduce type I collagen protein levels at either time point at any dose but slightly reduced alkaline phosphatase activity after 7 days. The messenger RNA (mRNA) levels for alkaline phosphatase, type I collagen, and osteonectin were unaltered by 24 h of ethanol treatment but a high dose (200 mM) reduced mRNA levels for the two bone matrix proteins after 7 days. Ethanol treatment led to dose-dependent increases in transforming growth factor ,1 (TGF-,1) mRNA levels and decreases in TGF-,2 mRNA levels. The concentration of ethanol in the medium decreased with time because of evaporation but there was little degradation caused by metabolism. These results, which show that cultured osteoblasts are less sensitive than osteoblasts in vivo, suggest that the pronounced inhibitory effects of ethanol on bone formation are not caused by direct cell toxicity. [source] Antimalarial activities of gedunin and 7-methoxygedunin and synergistic activity with dillapiolANNALS OF APPLIED BIOLOGY, Issue 2 2003S OMAR Summary Gedunin from Cedrela odorata (Meliaceae), a potent in vitro antimalarial agent, was investigated for its in vivo efficacy in CD-1 mice infected with Plasmodium berghei. When orally administered at 50 mg kg-1 day-1 for 4 days, gedunin was able to suppress the parasitaemia level by 44%. However, no clear dose-response effects were observed in the 0,100 mg kg-1 day-1 dose range. Preliminary pharmacokinetics in Sprague-Dawley rats showed poor absorption. However, a binary treatment of 50 mg kg-1 day-1 gedunin with 25 mg kg-1 day-1 dillapiol, a cytochrome P450 inhibitor, increased parasitaemia clearance in mice to 75%. A clear dose-response was observed in the 0,50 mg kg-1 day-1 gedunin dose range when administration was combined with 25 mg kg-1 day-1 dillapiol. In addition, 7-methoxygedunin, a semi-synthetic derivative which is more stable to degradation than gedunin, suppressed the level in mice by 67% at 50 mg kg-1 day-1. When administered at this dose in combination with 25 mg kg-1 day-1 dillapiol, clearance increased to 80%. These results demonstrate the potentialefficacy of antimalarial drugs and phytomedicines based on gedunin and the value of the combination therapy. [source] | ||||||||||