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Active Dose (active + dose)
Selected AbstractsDifferential time effect profiles of amlodipine, as compared to valsartan, revealed by ambulatory blood pressure monitoring, self blood pressure measurements and dose omission protocolFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 4 2004Anca Radauceanu Abstract Amlodipine and valsartan are once-daily antihypertensive agents. To date, no comparison between these agents given as monotherapies was reported. This study was aimed to evaluate the therapeutic coverage and safety of amlodipine and valsartan in mild-to-moderate hypertensive patients. Multicenter, double-blind, randomized, comparative study. After a 4-week placebo wash-out period, 246 outpatients with office diastolic blood pressure 95 , DBP ,110 mmHg and systolic blood pressure (SBP) < 180 mmHg, in addition to a mean daytime SBP and/or DBP > 135/85 mmHg on 24-h ambulatory blood pressure monitoring (ABPM), were randomly allocated to once-daily amlodipine 5,10 mg or valsartan 40,80 mg, for 12 weeks. In a subgroup of patients, 48-h ABPM were performed at the end of the treatment period. Dose omission was simulated by a single-blind placebo dosing. The primary efficacy end-point was the 24-h trough office BP after 12 weeks of active therapy. The reductions in 24-h trough BP were more pronounced in amlodipine compared with valsartan group as well in office [SBP: ,17.8 ± 10.9 vs. ,14.6 ± 11.2, P = 0.025, DBP: ,12.7 ± 7.2 vs. ,10.9 ± 7.8 mmHg, P = 0.06) as in ambulatory BP (SBP/DBP: ,13.0 ± 13.7/,10.8 ± 9.1 vs. ,7.2 ± 19.4/,4.9 ± 13.4 mmHg, P < 0.05). Forty-eight hours after the last active dose, the slope of the morning BP surge (4,9 h) was less steep with amlodipine vs. valsartan [DBP (P < 0.04), SBP (n.s.)]. Ankle edema were more often reported in amlodipine group. These results suggest a superior BP lowering and a longer duration of action with amlodipine compared with valsartan. [source] Atomistic analysis of B clustering and mobility degradation in highly B-doped junctionsINTERNATIONAL JOURNAL OF NUMERICAL MODELLING: ELECTRONIC NETWORKS, DEVICES AND FIELDS, Issue 4-5 2010Maria Aboy Abstract In this paper we discuss from an atomistic point of view some of the issues involved in the modeling of electrical characteristics evolution in silicon devices as a result of ion implantation and annealing processes in silicon. In particular, evolution of electrically active dose, sheet resistance and hole mobility has been investigated for high B concentration profiles in pre-amorphized Si. For this purpose, Hall measurements combined with atomistic kinetic Monte Carlo atomistic simulations have been performed. An apparent anomalous behavior has been observed for the evolution of the active dose and the sheet resistance, in contrast to opposite trend evolutions reported previously. Our results indicate that this anomalous behavior is due to large variations in hole mobility with active dopant concentration, much larger than that associated to the classical dependence of hole mobility with carrier concentration. Simulations suggest that hole mobility is significantly degraded by the presence of a large concentration of boron-interstitial clusters, indicating the existence of an additional scattering mechanism. Copyright © 2009 John Wiley & Sons, Ltd. [source] Disruptions in Functional Network Connectivity During Alcohol Intoxicated DrivingALCOHOLISM, Issue 3 2010Catherine I. Rzepecki-Smith Background:, Driving while under the influence of alcohol is a major public health problem whose neural basis is not well understood. In a recently published functional magnetic resonance imaging (fMRI) study (Meda et al., 2009), our group identified 5, independent critical driving-associated brain circuits whose inter-regional connectivity was disrupted by alcohol intoxication. However, the functional connectivity between these circuits has not yet been explored in order to determine how these networks communicate with each other during sober and alcohol-intoxicated states. Methods:, In the current study, we explored such differences in connections between the above brain circuits and driving behavior, under the influence of alcohol versus placebo. Forty social drinkers who drove regularly underwent fMRI scans during virtual reality driving simulations following 2 alcohol doses, placebo and an individualized dose producing blood alcohol concentrations (BACs) of 0.10%. Results:, At the active dose, we found specific disruptions of functional network connectivity between the frontal-temporal-basal ganglia and the cerebellar circuits. The temporal connectivity between these 2 circuits was found to be less correlated (p < 0.05) when driving under the influence of alcohol. This disconnection was also associated with an abnormal driving behavior (unstable motor vehicle steering). Conclusions:, Connections between frontal-temporal-basal ganglia and cerebellum have recently been explored; these may be responsible in part for maintaining normal motor behavior by integrating their overlapping motor control functions. These connections appear to be disrupted by alcohol intoxication, in turn associated with an explicit type of impaired driving behavior. [source] Cooperative antitumor effects of vitamin D3 derivatives and rosemary preparations in a mouse model of myeloid leukemiaINTERNATIONAL JOURNAL OF CANCER, Issue 12 2006Hagar Sharabani Abstract 1,,25-dihydroxyvitamin D3 (1,25D3) is a powerful differentiation agent, which has potential for treatment of myeloid leukemias and other types of cancer, but the calcemia produced by pharmacologically active doses precludes the use of this agent in the clinic. We have shown that carnosic acid, the major rosemary polyphenol, enhances the differentiating and antiproliferative effects of low concentrations of 1,25D3 in human myeloid leukemia cell lines (HL60, U937). Here we translated these findings to in vivo conditions using a syngeneic mouse leukemia tumor model. To this end, we first demonstrated that as in HL60 cells, differentiation of WEHI-3B D, murine myelomonocytic leukemia cells induced by 1 nM 1,25D3 or its low-calcemic analog, 1,25-dihydroxy-16-ene-5,6-trans-cholecalciferol (Ro25-4020), can be synergistically potentiated by carnosic acid (10 ,M) or the carnosic acid-rich ethanolic extract of rosemary leaves. This effect was accompanied by cell cycle arrest in G0+G1 phase and a marked inhibition of cell growth. In the in vivo studies, i.p. injections of 2 ,g Ro25-4020 in Balb/c mice bearing WEHI-3B D, tumors produced a significant delay in tumor appearance and reduction in tumor size, without significant toxicity. Another analog, 1,25-dihydroxy-16,23Z-diene-20-epi-26,27-hexafluoro-19-nor-cholecalciferol (Ro26-3884) administered at the same dose was less effective than Ro25-4020 and profoundly toxic. Importantly, combined treatment with 1% dry rosemary extract (mixed with food) and 1 ,g Ro25-4020 resulted in a strong cooperative antitumor effect, without inducing hypercalcemia. These results indicate for the first time that a plant polyphenolic preparation and a vitamin D derivative can cooperate not only in inducing leukemia cell differentiation in vitro, but also in the antileukemic activity in vivo. These data may suggest novel protocols for chemoprevention or differentiation therapy of myeloid leukemia. © 2006 Wiley-Liss, Inc. [source] Chronic Administration of Ketamine Elicits Antidepressant-Like Effects in Rats without Affecting Hippocampal Brain-Derived Neurotrophic Factor Protein LevelsBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 6 2008Lęda S. Garcia The present study was aimed to evaluate behavioural and molecular effects of the chronic treatment with ketamine and imipramine in rats. To this aim, rats were 14 days treated once a day with ketamine (5, 10 and 15 mg/kg) and imipramine (10, 20 and 30 mg/kg) and then subjected to the forced swimming and open-field tests. Ketamine and imipramine, at the all doses tested, reduced immobility time, and increased both climbing and swimming time of rats compared to the saline group, without affecting spontaneous locomotor activity. Brain-derived neurotrophic factor (BDNF) hippocampal levels were assessed in imipramine- and ketamine-treated rats by ELISA sandwich assay. Chronic administration of both drugs, ketamine and imipramine, did not modify BDNF protein levels in the rat hippocampus. In conclusion, our findings demonstrate for the first time that chronic administration of acute inactive doses of ketamine (5 mg/kg) becomes active after chronic treatment, while no signs of tolerance to the behavioural effects of ketamine were observed after chronic administration of acute active doses (10 and 15 mg/kg). Finally, these findings further support the hypothesis that NMDA receptor could be a new pharmacological target for the treatment of mood disorders. [source] | ||||||||||