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91.
92.
With the goal of developing soluble epoxide hydrolase (sEH) inhibitors with novel chemical structures, the sEH inhibitory activities of 30 natural compounds were evaluated using both a fluorescent substrate, 3-phenyl-cyano(6-methoxy-2-naphthalenyl)methyl ester- 2-oxiraneacetic acid, and a physiological substrate, 14,15-epoxyeicosatrienoic acid. To evaluate the selectivity of sEH inhibition, the inhibition of microsomal epoxide hydrolase (mEH), which plays a critical role in detoxification of toxic epoxides, was determined using human liver microsomes. Honokiol and β-amyrin acetate, isolated from Magnolia officinalis and Acer mandshuricum, respectively, displayed strong inhibition of sEH activity, with respective IC50 values of 0.57 μM and 3.4 μM determined using the fluorescent substrate, and 1.7 μM and 6.1 μM determined using 14,15-epoxyeicosatrienoic acid. mEH activity was decreased to 49% or 61% of control activity by 25 μM honokiol or β-amyrin acetate, respectively. These results suggest that β-amyrin acetate and honokiol exhibit sEH inhibitory activity, although their sEH selectivity should be improved. 相似文献
93.
BackgroundAbiraterone (ABI) is a major oral agent for the treatment of metastatic castration-resistant prostate cancer (mCRPC) patients but its systemic exposure is subject to a large inter-individual variability. We aimed to explore the relationship between ABI trough plasma concentration and prostate-specific antigen (PSA) response in mCRPC patients and to identify the critical determinants for its activity.Patients and methodsThis is a monocentric prospective observational study in mCRPC patients treated with ABI. The plasmatic concentration of ABI at steady state was measured using liquid chromatography with fluorescence detection. The primary objective was to study the relationship between mean ABI plasma exposure (ABI Cmin) and 3-month PSA response.ResultsFrom 2012 to 2016, 61 mCRPC patients were eligible for pharmacokinetic/pharmacodynamic assessment. Thirty-eight patients experienced PSA response (62%, [confidence interval {CI} 95% 50–78]). In univariate analysis, ABI Cmin was 1.5-fold higher in responders: 12.0 ng/mL (CI 95% 9.4–15.6) versus 8.0 ng/mL (CI 95% 5.8–11.6; P = 0.0015). In multivariate analysis, only ABI Cmin was independently associated with PSA response (odds ratio = 1.12 [CI 95% 1.01–1.25], P = 0.004). By receiver operating characteristic analysis, the optimal threshold for ABI Cmin was 8.4 ng/mL. Progression-free survival (PFS) was significantly higher in patients with ABI Cmin above 8.4 ng/mL (hazard ratio 0.55, [CI 95% 0.31–0.99], 12.2 [CI 95% 9.2–19.5] versus 7.4 [CI 95% 5.5–14.7] months otherwise, P = 0.044).ConclusionsWe showed that ABI trough concentration correlates with PSA response and PFS. Moreover, we could determine a cut-off value of plasmatic concentration for PSA response. Altogether, ABI concentration monitoring appears as a new approach to improve clinical outcome in mCPRC patients. 相似文献
94.
The objective of this work was to develop uniformly distributed poly(ethylene glycol) grafted poly(lactide-co-glycolide) (PEG-PLGA) nanoparticles of mean size range ~100–200 nm using ethyl acetate as the solvent. In the multiple emulsion solvent evaporation method a high pressure microfluidization process was adopted to produce the W/O/W multiple emulsion. Non-toxic ethyl acetate was used to solubilize PEG-PLGA. The mean size of nanoparticles obtained was less than 180 nm. The particle size and size distribution were dependent on the microfluidization conditions applied. Mean particle size steadily increased from 121 nm at three passes to 172 nm at 20 passes of the microfluidizer, indicating that over-processing may be detrimental to PEG-PLGA nanoparticles prepared using this technique. There was no significant alteration of the PEG-PLGA matrix, as evidenced from the differential scanning calorimetric studies. 相似文献
95.
Progestin‐primed ovarian stimulation with or without clomiphene citrate supplementation in normal ovulatory women undergoing in vitro fertilization/intracytoplasmic sperm injection: A prospective randomized controlled trial 下载免费PDF全文
96.
97.
《Journal of drug targeting》2013,21(6):487-492
AbstractThe effects of concentration, amperage and duration on the antidiuretic response induced by iontophoretic delivery of desmopressin acetate (DDAVP) were examined using a diabetes insipidus model in rats. A higher current density brought about a larger and longer antidiuretic response. Prolonged iontophoretic duration caused an overdose. Repeated short iontophoretic treatments with lower current density maintained a constant response with a short lag time and a rapid disappearance of pharmacological response immediately after cessation of the final treatment. This type of iontophoresis substantially reduced the inter-subject variability of response as compared to the response using an intranasal route of administration. 相似文献
98.
《Artificial organs》2017,41(6):509-518
Hemodialysis patients can acquire buffer base (i.e., bicarbonate and buffer base equivalents of certain organic anions) from the acid and base concentrates of a three‐stream, dual‐concentrate, bicarbonate‐based, dialysis solution delivery machine. The differences between dialysis fluid concentrate systems containing acetic acid versus sodium diacetate in the amount of potential buffering power were reviewed. Any organic anion such as acetate, citrate, or lactate (unless when combined with hydrogen) delivered to the body has the potential of being converted to bicarbonate. The prescribing physician aware of the role that organic anions in the concentrates can play in providing buffering power to the final dialysis fluid, will have a better knowledge of the amount of bicarbonate and bicarbonate precursors delivered to the patient. 相似文献
99.
《药学学报(英文版)》2020,10(2):327-343
Our recent studies demonstrated that the natural product nobiletin (NOB) served as a promising multidrug resistance (MDR) reversal agent and improved the effectiveness of cancer chemotherapy in vitro. However, low aqueous solubility and difficulty in total synthesis limited its application as a therapeutic agent. To tackle these challenges, NOB was synthesized in a high yield by a concise route of six steps and fourteen derivatives were synthesized with remarkable solubility and efficacy. All the compounds showed improved sensitivity to paclitaxel (PTX) in P-glycoprotein (P-gp) overexpressing MDR cancer cells. Among them, compound 29d exhibited water solubility 280-fold higher than NOB. A drug-resistance A549/T xenograft model showed that 29d, at a dose of 50 mg/kg co-administered with PTX (15 mg/kg), inhibited tumor growth more effective than NOB and remarkably increased PTX concentration in the tumors via P-gp inhibition. Moreover, Western blot experiments revealed that 29d inhibited expression of NRF2, phosphorylated ERK and AKT in MDR cancer cells, thus implying 29d of multiple mechanisms to reverse MDR in lung cancer. 相似文献
100.
Paola L. Minciullo Gioacchino Calapai Sebastiano Gangemi 《Allergy, asthma & immunology research》2014,6(5):467-469
Glatiramer acetate (GA) is a synthetic amino acid polymer, used for relapsing-remitting multiple sclerosis. The most common adverse effect of GA is a skin reaction at the injection site with a probable IgE-mediated mechanism. We report a case of a 45-year-old woman with multiple sclerosis and urticaria to interferon-β1a, who underwent a challenge test to GA. She presented itching wheals at the intradermal sites. A month later the patient repeated the test and presented the same reactions of the first test. The next day she continued the test with subcutaneous injections. One hour later she presented a flare up of the reactions appeared during the previous 2 tests. No reactions appeared at the subcutaneous injection sites. The patient also presented dyspnea. Flare-up reactions are characterized by the reactivation of previously positive reactions to intradermal or skin tests triggered by patch testing and after systemic provocation with an allergen. The phenomenon is not common to drugs. The mechanisms involved in this reaction seem to be heterogeneous and are not completely understood. To our knowledge this is the first case of allergic reaction to GA manifested as a flare-up reaction during challenge test. 相似文献