This study presents a new two compartmental model and its application to the evaluation of diclofenac pharmacokinetics in a small number of healthy adults, during a bioequivalence trial. In the model the integer order derivatives are replaced by derivatives of real order often called fractional order derivatives. Physically that means that a history (memory) of a biological process, realized as a transfer from one compartment to another one with the mass balance conservation, is taken into account. This kind of investigations in pharmacokinetics is founded by Dokoumetzidis and Macheras through the one compartmental models while our contribution is the analysis of multi-dimensional compartmental models with the applications of the two compartmental model in evaluation of diclofenac pharmacokinetics. Two experiments were preformed with 12 healthy volunteers with two slow release 100 mg diclofenac tablet formulations. The agreement of the values predicted by the proposed model with the values obtained through experiments is shown to be good. Thus, pharmacokinetics of slow release diclofenac can be described well by a specific two compartmental model with fractional derivatives of the same order. Parameters in the model are determined by the least-squares method and the Particle Swarm Optimization (PSO) numerical procedure is used. The results show that the fractional order two compartmental model for diclofenac is superior in comparison to the classical two compartmental model. Actually this is true in general case since the classical one is a special case of the fractional one.
Resveratrol (trans-3,5,4'-trihydroxystilbene) is a phytoalexin produced by grapevines in response to fungal infection, particularly to Botrytis cinerea. It has been shown that it possess various biological effects such as prevention of cardiovascular diseases and anti-inflammatory and anticancerogenic properties. Red wines are a primary source of resveratrol. Although a number of investigations have focused on the determination of resveratrol in wines of different countries, there is no similar study about the wines produced in Serbia. As authors are aware, the only study concerning resveratrol content in wine in the Balkan region was conducted in Greece. In this study, the trans- and cis-resveratrol content in samples obtained from 18 commercial Serbian wines (10 red, 7 white, and 1 rose) were analyzed. Analyses were performed after solid-phase extraction by high-performance liquid chromatography with a diode array detection system using an RP-C(18) column with gradient elution [solvent A: acetonitrile-acetic acid-water (20:2:78 v/v), solvent B: acetonitrile-acetic acid-water (90:2:8 v/v)]. Detection of trans- and cis-resveratrol was performed on 306 and 286 nm, respectively. It was clearly established that there was a presence of trans-resveratrol isomers in all analyzed wines (0.11-1.69 mg/L) except in one white wine. Cis-resveratrol was present in 12 from 18 samples in different amounts (0.12-1.49 mg/L).
Twenty soybean cultivars, originating from the United States, Russia, Serbia, and China, were analyzed for their isoflavone composition, total polyphenolic content, and antioxidant activity. Isoflavones were extracted by aqueous methanol (80%) and analyzed by high-performance liquid chromatography=diode array detection. Precision and linearity of the applied method were within the standard limits of validation. The highest and the lowest total isoflavone contents were 4.59 and 1.45 mg=g of dried soybean weight, respectively. A significant difference (P < .05) was found in isoflavone concentration among the different cultivars, but it was observed that origin is not a significant factor that could influence isoflavone content in soybeans. Total polyphenolic content varied between 2.13 and 3.45 mg of gallic acid equivalents=g of dried soybean weight. The free radical scavenging activity of soybean extracts assayed by 2,2-diphenyl-1-picrylhydrazyl in terms of 50% inhibitory concentration (IC 50 ) ranged from 1.40 to 3.35 mg=mL. Negative correlation between total polyphenolic content and IC 50 was observed, but there was no correlation between total isoflavone content and IC 50 . On the basis of this study, soybean cultivars with larger potency for biological activity could be recognized.KEY WORDS: 2,2-diphenyl-1-picrylhydrazyl assay high-performance liquid chromatography analysis soybean phytoestrogens
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