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991.
992.
Chong-Ki Lee Jun-Shik Choi Joon Seok Bang 《The Korean journal of physiology & pharmacology》2013,17(3):245-251
The purpose of this study was to investigate the effects of fluvastatin on the pharmacokinetics of repaglinide in rats. The effect of fluvastatin on P-glycoprotein and CYP3A4 activity was evaluated. The pharmacokinetic parameters and blood glucose concentrations were also determined after oral and intravenous administration of repaglinide to rats in the presence and absence of fluvastatin. Fluvastatin inhibited CYP3A4 activity in a concentration-dependent manner with a 50% inhibition concentration(IC50) of 4.1 µM and P-gp activity. Compared to the oral control group, fluvastatin significantly increased the AUC and the peak plasma level of repaglinide by 45.9% and 22.7%, respectively. Fluvastatin significantly decreased the total body clearance (TBC) of repaglinide compared to the control. Fluvastatin also significantly increased the absolute bioavailability (BA) of repaglinide by 46.1% compared to the control group. Moreover, the relative BA of repaglinide was 1.14- to 1.46-fold greater than that of the control. Compared to the i.v. control, fluvastatin significantly increased the AUC0-∞ of i.v. administered repaglinide. The blood glucose concentrations showed significant differences compared to the oral controls. Fluvastatin enhanced the oral BA of repaglinide, which may be mainly attributable to the inhibition of the CYP3A4-mediated metabolism of repaglinide in the small intestine and/or liver, to the inhibition of the P-gp efflux transporter in the small intestine and/or to the reduction of TBC of repaglinide by fluvastatin. The study has raised the awareness of potential interactions during concomitant use of repaglinide with fluvastatin. Therefore, the concurrent use of repaglinide and fluvastatin may require close monitoring for potential drug interactions. 相似文献
993.
《Pharmaceutical biology》2013,51(9):1073-1078
Context: The pharmaceutical alkaloid huperzine A (HupA), currently used in herbal supplements and medicines worldwide, is predominantly sourced from the Chinese lycopod Huperzia serrata (Thunb. ex Murray) Trev. (Lycopodiaceae), which on average contains only 0.08?mg HupA g?1 dry weight, and is experiencing a rapid decline in China due to over-harvesting.Objective: To find a high-yielding, natural source of HupA and/or the related huperzine B (HupB) that could potentially be used as the starting material in a commercial propagation program.Materials and methods: We surveyed 17 Huperzia species (15 indigenous to Australia and southeast Asia) for their foliar HupA and HupB concentrations. We also studied intra-specific variation for the huperzines in four species that were available in sufficient numbers, and determined tissue-specific accumulation in larger specimens.Results: HupA was detected in 11 Australasian and southeast Asian species, with eight also containing HupB, albeit at much lower concentrations. A H. elmeri (Herter) Holub plant from the Philippines had one of the highest HupA concentrations recorded (1.01?mg g?1 dry wt) and it also had the highest HupB content of all plants surveyed (0.34?mg g?1 dry wt). Intra-specific HupA and HupB concentrations were extremely variable, and at the intra-plant level, reproductive strobili were found to accumulate the highest HupA concentrations.Discussion and conclusion: Select Huperzia species from Australia and southeast Asia have potential as the starting material for establishing commercial HupA plantations, but the high intra-specific variability observed suggests that detailed screening is needed to isolate high huperzine-yielding individuals. 相似文献
994.
Eleutheroside B or E, the main component of Acanthopanax, can relieve fatigue, enhance memory, and improve human cognition. Numerous studies have confirmed that high doses of acetylcholine significantly attenuate clinical symptoms and delay the progression of Alzheimer’s disease. The present study replicated a rat model of aging induced by injecting quinolinic acid into the hippocampal CA1 region. These rats were intraperitoneally injected with low, medium and high doses of eleutheroside B or E (50, 100, 200 mg/kg), and rats injected with Huperzine A or PBS were used as controls. At 4 weeks after administration, behavioral tests showed that the escape latencies and errors in searching for the platform in a Morris water maze were dose-dependently reduced in rats treated with medium and high-dose eleutheroside B or E. Hematoxylin-eosin staining showed that the number of surviving hippocampal neurons was greater and pathological injury was milder in three eleutheroside B or E groups compared with model group. Hippocampal homogenates showed enhanced cholinesterase activity, and dose-dependent increases in acetylcholine content and decreases in choline content following eleutheroside B or E treatment, similar to those seen in the Huperzine A group. These findings indicate that eleutheroside B or E improves learning and memory in aged rats. These effects of eleutheroside B or E may be mediated by activation of cholinesterase or enhanced reuse of choline to accelerate the synthesis of acetylcholine in hippocampal neurons. 相似文献
995.
Rubabe S. Saharan MSc 《The journal of spinal cord medicine》2013,36(5):520-526
AbstractBackground/Objective: Adenosine A1 receptors localized in the phrenic motoneurons (PMNs), where the axons of the descending bulbospinal respiratory make synaptic contacts, may be involved in theophylline- induced respiratory-related activity in rats. The objective of this study was to characterize the biochemical profiles of adenosine A., receptors in 2 groups of rats: (a) naive and (b) theophylline-treated (3-day oral administration).Methods: Biochemical binding characteristics of adenosine A1 receptors in the C3 to C5 (PMN) of adult rats were assessed in naive (n = 6) and theophylline-treated animals (n = 6) using [3H]-DPCPX (10 pmol/L to 30 nmol/L), the specific adenosine A1 receptor antagonist in saturation-binding assays. Competition assays used theophylline as the competing ligand (20 mmol/L to 20 pmol/L), and protein concentration was determined with the Bradford assay using a range of standards (0.016-1.0 mg/mL).Results: In saturation-binding assays in naive animals, the A1 receptor was characterized by a single binding site with Smax and Kd values of 256.00 ± 32.13 fmoi/mg protein and 2.89 ± 0.45 nmol/L, respectively. Analysis of the isotherm in theophylline-treated animals showed 1 site with Smax and Kd values of 219.00 ± 26.3 fmol/mg protein and 0.60 ± 0.21 nmol/L, respectively, and a second site characterized by Smax and Kd values of 492.6 ± 3.15 fmol/mg protein and 14.09 ± 2.06 n mol/L, respectively.Conclusions: Theophylline administration revealed 2 binding sites on receptors (characterized by the specific adenosine A1 antagonist, [3H]-DPCPX) located in the vicinity of phrenic motoneurons (C3-C5). Alteration of the receptor profiles after theophylline may underlie the respiratory-related actions of the drug. 相似文献
996.
997.
《Gut microbes》2013,4(6):392-397
Intestinal immunity is subject to complex and fine-tuned regulation dictated by interactions of the resident microbial community and their gene products with host innate cells. Deterioration of this delicate process may result in devastating autoinflammatory diseases, including inflammatory bowel disease (IBD), which primarily comprises Crohn's disease (CD) and ulcerative colitis (UC). Efficacious interventions to regulate proinflammatory signals, which play critical roles in IBD, require further scientific investigation. We recently demonstrated that rebalancing intestinal immunity via the surface layer protein A (SlpA) from Lactobacillus acidophilus NCFM potentially represents a feasible therapeutic approach to restore intestinal homeostasis. To expand on these findings, we established a new method of purifying bacterial SlpA, a new SlpA-specific monoclonal antibody, and found no SlpA-associated toxicity in mice. Thus, these data may assist in our efforts to determine the immune regulatory efficacy of SlpA in humans. 相似文献
998.
999.
1000.
Tomáš Radil MD DSc 《Medicine, conflict, and survival》2013,29(2):161-162
Science and Conscience In the Shadow of the Bomb: Oppenheimer, Bethe, and the Moral Responsibility of the Scientist By Silvan S. Schweber Princeton University Press, Princeton NJ, 2000, 260 pp., £15.95, ISBN 0–691–04989–0. Sanctions Iraq Under Siege: The Deadly Impact of Sanctions and War Edited by Anthony Amove Pluto, London, 2000, 224 pp., £10.99 pbk. ISBN 0–7453–16S9‐X, £35.00 hbk, ISBN 0–7453–1660–3. Nurses at War Nurses at War: Women on the Frontline 1939–45 By Penny Starns Sutton, Stroud, 2000, xvii + 174 pp., £19.99 hbk, ISBN 0–7509–23873. Peace Education Saying No to Violence — Children and Peace: Activities for a Peaceful World By Jan Melichar and Margaret Melicharova Peace Pledge Union, London, 2000, 58 pp., £9.99, ISBN 0–902680–46–3. 相似文献