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Multiple Administrations (multiple + administration)
Selected AbstractsEnamel matrix derivative enhances tissue formation around scaffolds used for tissue engineering of ligamentsJOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, Issue 2 2010Michael P. Messenger Abstract The following in vitro translational study investigated whether enamel matrix derivative (EMD), an approved biomimetic treatment for periodontal disease (Emdogain®) and hard-to-heal wounds (Xelma®), enhanced synovial cell colonization and protein synthesis around a scaffold used clinically for in situ tissue engineering of the torn anterior cruciate ligament (ACL). Synovial cells were enzymatically extracted from bovine synovium and dynamically seeded onto polyethylene terephthalate (PET) scaffolds. The cells were cultured in low-serum medium (0.5% FBS) for 4 weeks with either a single administration of EMD at the start of the 4 week period or multiple administrations of EMD at regular intervals throughout the 4 weeks. Samples were harvested and evaluated using the Hoechst DNA assay, BCA protein assay, cresolphthalein complexone calcium assay, SDS,PAGE, ELISA and electron microscopy. A significant increase in cell number (DNA) (p < 0.01), protein content (p < 0.01) and TGF,1 synthesis (p < 0.01) was observed with multiple administrations of EMD. Additionally, SDS,PAGE showed an increase in high molecular weight proteins, characteristic of the fibril-forming collagens. Electron microscopy supported these findings, showing that scaffolds treated with multiple administrations of EMD were heavily coated with cells and extracellular matrix (ECM) that enveloped the fibres. Multiple administrations of EMD to synovial cell-seeded scaffolds enhanced the formation of tissue in vitro. Additionally, it was shown that EMD enhanced TGF,1 synthesis of synovial cells, suggesting a potential mode of action for EMD's capacity to stimulate tissue regeneration. Copyright © 2009 John Wiley & Sons, Ltd. [source] Comparison of single vs. multiple administrations of the AMPA receptors modulator S 18986 in the object recognition task in ratsFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 4 2007V. Bertaina-Anglade Abstract The present study aimed at defining the best scheme of administration of the , -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-positive modulator (S)-2,3-dihydro-[3,4]-cyclopentano-1,2,4-benzothiadiazine-1,1-dioxide (S 18986) [once daily (o.d.) administration of 1 mg/kg for 3 days vs. three times daily (t.i.d.) administration of 0.3 mg/kg for 3 days] to get an optimal procognitive activity in the object recognition task in rats. Memory performance [Recognition Index (RI)] of rats was significantly improved 1 h (RI = 41%, P < 0.01) and 3 h (RI = 46%, P < 0.001) following oral administration of S 18986 (1 mg/kg, o.d.) when compared with animals receiving the vehicle (RI = 6%). When the interval between administration and testing was increased to 6 h and 9 h, no statistically significant improvement in memory performance was observed (RI = 42% for 6 h and RI = 18% for 9 h vs. 20% for the vehicle group). When S 18986 was administered at 0.3 mg/kg t.i.d., no statistically significant improvement in memory performance was observed (RI = 36%). These findings show a long-lasting efficacy of the AMPA receptor allosteric modulator in the object recognition task despite a short half-life in plasma and in brain (approximately 1 h). Accordingly, multiple administrations of S 18986 are not required to obtain a maximal efficacy in this paradigm, because a o.d. schedule of administration leads to a powerful procognitive activity. [source] Enamel matrix derivative enhances tissue formation around scaffolds used for tissue engineering of ligamentsJOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, Issue 2 2010Michael P. Messenger Abstract The following in vitro translational study investigated whether enamel matrix derivative (EMD), an approved biomimetic treatment for periodontal disease (Emdogain®) and hard-to-heal wounds (Xelma®), enhanced synovial cell colonization and protein synthesis around a scaffold used clinically for in situ tissue engineering of the torn anterior cruciate ligament (ACL). Synovial cells were enzymatically extracted from bovine synovium and dynamically seeded onto polyethylene terephthalate (PET) scaffolds. The cells were cultured in low-serum medium (0.5% FBS) for 4 weeks with either a single administration of EMD at the start of the 4 week period or multiple administrations of EMD at regular intervals throughout the 4 weeks. Samples were harvested and evaluated using the Hoechst DNA assay, BCA protein assay, cresolphthalein complexone calcium assay, SDS,PAGE, ELISA and electron microscopy. A significant increase in cell number (DNA) (p < 0.01), protein content (p < 0.01) and TGF,1 synthesis (p < 0.01) was observed with multiple administrations of EMD. Additionally, SDS,PAGE showed an increase in high molecular weight proteins, characteristic of the fibril-forming collagens. Electron microscopy supported these findings, showing that scaffolds treated with multiple administrations of EMD were heavily coated with cells and extracellular matrix (ECM) that enveloped the fibres. Multiple administrations of EMD to synovial cell-seeded scaffolds enhanced the formation of tissue in vitro. Additionally, it was shown that EMD enhanced TGF,1 synthesis of synovial cells, suggesting a potential mode of action for EMD's capacity to stimulate tissue regeneration. Copyright © 2009 John Wiley & Sons, Ltd. [source] A single versus multiple doses of dexamethasone in infants wheezing for the first timePEDIATRIC PULMONOLOGY, Issue 9 2008Suzanne Schuh MD Abstract Rationale: Corticosteroid therapy is not routinely recommended in true bronchiolitis. However, since bronchiolitis and the first asthma attack are impossible to distinguish, some infants with the first wheezing episode receive corticosteroids. Optimal duration of corticosteroid therapy in this scenario is unknown. This study compared efficacy of multiple administrations and a single dose of dexamethasone in bronchiolitis. Methods: In this randomized double blind trial, previously healthy outpatients 2,23 months of age with bronchiolitis and Respiratory Disease Assessment Instrument (RDAI) score 6 or more received 1 mg/kg of oral dexamethasone in the Emergency Department. Prior to discharge at 4 hr they were randomized to either 4 daily doses of dexamethasone 0.15 mg/kg or placebo equivalent. Primary outcome was the proportion of subsequent hospitalizations or prescribed trials of bronchodilator/corticosteroid therapy for dyspnea by day 6 in the groups. Secondary outcomes were changes in the RDAI to day 6, and proportions with unscheduled visits by days 6 and 28. Results: The rate of primary outcome in the single dose group (SDG, N,=,64) was 9/64 or 14.1% versus 7/61 or 11.5% in the multiple dose group (MDG, N,=,61) [95% CI 0.09; 0.14]. Twelve (18.8%) children in the SDG had unscheduled medical visits by day 6 versus 11 (18.0%) children in the MDG [95% CI 0.13; 0.14]. On day 6 the RDAI decreased from 9.5,±,2.1 to 2.1,±,2.4 in the SDG and from 9.8,±,2.2 to 1.6,±,2.3 in the MDG [95% CI 0.36; 2.06]. Between days 7,28, 24/64 (37.5%) SDG infants returned for care versus 20/61 (32.8%) of the MDG [95% CI 0.12; 0.21]. Conclusions: Our study suggests that, in outpatients with bronchiolitis who receive dexamethasone, continuation of this agent beyond the initial dose does not provide significant benefit. Pediatr Pulmonol. 2008; 43:844,850. © 2008 Wiley-Liss, Inc. [source] Effects of Angelicae tenuissima radix, Angelicae dahuricae radix and Scutellariae radix Extracts on Cytochrome P450 Activities in Healthy VolunteersBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 4 2009SoJeong Yi A total of 24 healthy male volunteers were assigned to one of three parallel herbal treatment groups, each consisting of eight volunteers. A cocktail of probe drugs for CYP enzymes was orally administered before and after multiple administrations of herbal medicines, three times a day for 13 days. Probe drugs used to measure CYP activities were caffeine (CYP1A2), losartan (CYP2C9), omeprazole (CYP2C19), dextromethorphan (CYP2D6), chlorzoxazone (CYP2E1) and midazolam (CYP3A4). The probe drugs and their metabolites were quantified in plasma or urine using HPLC or LC-MS/MS. Changes in each CYP activity was evaluated by metabolic ratio of the probe drug (concentration ratio of metabolite to parent form at reference time point) following the herbal medication period, compared to the baseline values. A. dahuricae radix significantly decreased CYP1A2 activity to 10% of baseline activity (95% CI: 0.05,0.21). S. radix also showed significant changes in CYP2C9 and CYP2E1 activities. Compared to baseline values, the metabolic activities of losartan were decreased to 71% (0.54,0.94). In addition, S. radix showed a 1.42-fold (1.03,1.97) increase in chlorzoxazone metabolic activity. However, CYP activities were not meaningfully influenced by A. tenuissima radix. Changes in certain CYP activities were observed after the administration of S. radix and A. dahuricae radix in healthy volunteers. Therefore, herbal medicines containing S. radix or A. dahuricae radix are candidates for further evaluation of clinically significant CYP-mediated herb-drug interactions in human beings. [source] | ||||||||||