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Tested Doses (tested + dose)
Selected AbstractsPharmacokinetic,pharmacodynamic study of apomorphine's effect on growth hormone secretion in healthy subjectsFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 4 2003Guy Aymard Abstract Apomorphine (APO) stimulates growth hormone (GH) release via dopamine D2 receptors (DRD2). There is no specific study assessing the relationship between APO pharmacokinetic (PK) and the pharmacodynamic (PD) response e.g. GH release. The objective of the study is the PK,PD modelling of APO in healthy subjects. This is a randomized crossover study with s.c. administration of 5, 10, and 20 ,g/kg of APO in 18 healthy subjects. APO concentrations were modelled according to both a bi-compartmental model with zero-order absorption and a bi-compartmental model with first-order absorption. PK,PD relationship was modelled in accordance with the Emax Hill equation using plasma concentrations of APO calculated according to the bi-compartmental model with zero-order absorption. Modelled parameters were very similar to the experimental parameters. PK of APO was linear and there was no significant difference between the tested doses for AUC0,, and Cmax (normalised to the dose 1 ,g/kg), t1/2, and t1/2,. These parameters expressed as mean (CV%: SD/mean) were: 17.2 (26.9) ng/mL·min, 0.26 (33.3) ng/mL, 17.1 (54.2) and 45.2 (20.6) min, respectively (n = 53). An anticlockwise hysteresis loop (effect function of APO plasma concentration) appeared for each dose and each subject. The predicted and measured GH concentrations for all subjects and times were similar whatever the dose (P > 0.27). Emax values were 246 (121), 180 (107), 205 (139) ng/mL, respectively, and EC50 were 0.98 (48.1), 1.70 (62.3), 3.67 (65.2) ng/mL, respectively at dose 5, 10, and 20 ,g/kg (P < 10,4). APO and GH concentrations were predicted with good accuracy using bi-compartmental with zero-order absorption PK model and sigmoid Emax PD model, respectively. [source] (11Z)-hexadec-11-enal enhances the attractiveness of Diatraea saccharalis main pheromone component in wind tunnel experimentsJOURNAL OF APPLIED ENTOMOLOGY, Issue 2 2005B. Kalinová Abstract:, GC-EAD and GC-MS analysis of pheromone gland extracts of sugarcane borer, Diatraea saccharalis, revealed two antennally active compounds, (9Z,11E)-hexadeca-9,1-dienal and (11Z)-hexadec-11-enal, in approximately 10 : 1 ratio. Various doses of identified compounds were investigated in wind tunnel experiments individually and in a 10 : 1 ratio. At all tested doses (9Z,11E)-hexadeca-9,1-dienal alone elicited upwind orientation and source location only in a minority of tested males. An admixture of (11Z)-hex-11-enal enhanced the attractiveness of (9Z,11E)-hexadeca-9,11-dienal significantly. This two-component blend (100 pg) was as attractive as natural pheromone extracted from three female pheromone glands. The data suggest that (11Z)-hexadec-11-enal is a part of the D. saccharalis sex pheromone. [source] Dichloroacetate- and trichloroacetate-induced oxidative stress in the hepatic tissues of mice after long-term exposureJOURNAL OF APPLIED TOXICOLOGY, Issue 5 2010Ezdihar A. Hassoun Abstract Dichoroacetate (DCA) and trichloroacetate (TCA) were found to be hepatotoxic and hepatocarcinogenic in rodents. To investigate the role of oxidative stress in the long-term hepatotoxicity of the compounds, groups of mice were administered 7.7, 77, 154 and 410,mg,kg,1 per day, of either DCA or TCA, by gavage, for 4 weeks (4-W) and 13 weeks (13-W), and superoxide anion (SA), lipid peroxidation (LP) and DNA-single strand breaks (SSBs) were determined in the hepatic tissues. Significant increases in all of the biomarkers were observed in response to the tested doses of both compounds in the two test periods, with significantly greater increases observed in the 13-W, as compared with the 4-W, period. Hepatomegaly was only observed with a DCA dose of 410,mg,kg,1 per day in the 13-W treatment period, and that was associated with significant declines in the biomarkers, when compared with the immediately lower dose. With the exception of LP production in the 13-W treatment period that was similarly induced by the two compounds, the DCA-induced increases in all of the biomarkers were significantly greater than those of TCA. Since those biomarkers were significantly induced by the compounds' doses that were shown to be carcinogenic but at earlier periods than those demonstrating hepatotoxicity/haptocarcinogencity, they can be considered as initial events that may lead to later production of those long-term effects. The results also suggest LP to be a more significant contributing mechanism than SA and DNA damage to the long-term hepatotoxicity of TCA. Copyright © 2010 John Wiley & Sons, Ltd. [source] Effect of Sequential Treatment of Warm Water Dip and Low-dose Gamma Irradiation on the Quality of Fresh-cut Green OnionsJOURNAL OF FOOD SCIENCE, Issue 3 2005Hyun Jung Kim ABSTRACT: The effect of warm water dip in combination with irradiation on quality of fresh-cut green onions was studied. Fresh-cut green onions were treated with and without warm water (50°C for 20 s) and packaged prior to irradiation at 0, 0.5, 1.0, and 1.5 kGy, then stored at 4°C for 14 d. Color, texture, decay percentage, electrolyte leakage, sensory qualities, and total aerobic count (TAC) were measured at 1,4,8, and 14 d of storage. The warm water treatment reduced the TAC by 0.9 log initially but the beneficial effect disappeared during storage. With the test conditions used in this study, the warm water treatment did not provide added benefits for quality improvements. Irradiation at all tested doses reduced TAC and the development of decay and off-odor, improved visual quality, and preserved green color. [source] Does an Energy Drink Modify the Effects of Alcohol in a Maximal Effort Test?ALCOHOLISM, Issue 9 2004Sionaldo Eduardo Ferreira Background: There are popular reports on the combined use of alcohol and energy drinks (such as Red Bull® and similar beverages, which contain caffeine, taurine, carbohydrates, etc.) to reduce the depressant effects of alcohol on central nervous system, but no controlled studies have been performed. The main purpose of this study was to verify the effects of alcohol, and alcohol combined with energy drink, on the performance of volunteers in a maximal effort test (cycle ergometer) and also on physiological indicators (oxygen uptake, ventilatory threshold, respiratory exchange rate, heart rate, and blood pressure), biochemical variables (glucose, lactate, insulin, cortisol, ACTH, dopamine, noradrenaline, and adrenaline), and blood alcohol levels. Methods: Fourteen healthy subjects completed a double-blind protocol made up of four sessions: control (water), alcohol (1.0 g/kg), energy drink (3.57 ml/kg Red Bull®), and alcohol + energy drink, each 1 week apart. The effort test began 60 min after drug or control ingestion, and the dependent variables were measured until 60 min after the test. Results: Heart rate at the ventilatory threshold was higher in the alcohol and alcohol + energy drink sessions in comparison with control and energy drink sessions. Although in comparison to the control session, the peak oxygen uptake was 5.0% smaller after alcohol ingestion, 1.4% smaller after energy drink, and 2.7% smaller after the combined ingestion, no significant differences were detected. Lactate levels (30 min after drug ingestion, 30 and 60 min after the effort test) and noradrenaline levels (30 min after the effort test) were higher in the alcohol and alcohol + energy drink sessions compared with the control session. Conclusions: The performance in the maximal effort test observed after alcohol + energy drink ingestion was similar to that observed after alcohol only. No significant differences between alcohol and alcohol + energy drink were detected in the physiological and biochemical parameters analyzed. Our findings suggest that energy drinks, at least in the tested doses, did not improve performance or reduce alterations induced by acute alcohol ingestion. [source] Activity of NADPH-Cytochrome P-450 Reductase of the Human Heart, Liver and Lungs in the Presence of (-)-Epigallocatechin Gallate, Quercetin and Resveratrol: An in vitro StudyBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 2 2005Jaroslaw Dudka The enzyme is also involved in the toxicity of some clinically important antitumour drugs (doxorubicin) and pesticides (paraquat). P-450 reductase activates them to their more toxic metabolites via one electron reduction which triggers free radical cascade. In some cases however, such transformation is essential to produce therapeutic effect in anticancer drugs. The main purpose of the paper was to evaluate the effect of three natural compounds found in human diet: (-)-epigallocatechin gallate (EGCG), quercetin and resveratrol on P-450 reductase activity. The activity of the enzyme was determined spectrophotometrically by measurement of the rate of cytochrome c reduction at 550 nm, in vitro, using human heart, liver and lung microsomes. It was found that quercetin increased the P-450 reductase activity in human organs at all tested doses. The activity of microcosms in all organs was enhanced according to the concentrations of quercetin, which increased the activity in the order lung>heart>liver. Addition of EGCG to the reaction mixture enhanced the P-450 reductase activity in the following order: liver>heart>lung. However, no significant effect of resveratrol on P-450 reductase activity was observed. It seems that the presence of quercetin and EGCG in the diet may increase P-450 reductase activity during doxorubicin therapy with subsequent increased risk of toxicity. A beneficial effect may be obtained in anticancer therapy with bioreductive agents like tirapazamine. [source] | |||||||||||||