Amifostine, a radioprotectant agent, protects rat brain tissue lipids against ionizing radiation induced damage: an FTIR microspectroscopic imaging study

The ABC proteins are a family of membrane transporters that mediates the extrusion from cells of a wide variety of structurally unrelated substrates. The current review focuses on the role of these efflux pumps located in the intestine on the low oral bioavailability of trans-resveratrol. The enterocytes hold in the apical membrane three transporters, namely, P-glycoprotein (P-gp), multidrug resistance associated protein 2 (MRP2) and breast cancer resistance protein (BCRP), whereas the basolateral membrane contains multidrug resistance associated protein 3 (MRP3). The use of different specific inhibitors of these transporters as well as knockout mice enabled us to conclude that MRP2 and BCRP are involved in the extrusion of trans-resveratrol glucuronide and sulfate to the intestinal lumen without the participation of P-gp. The role of these transporters as a bottleneck in the absorption of trans-resveratrol cannot be undervalued affecting not only the bioavailability of its glucuronide and sulfate but also their distribution in the different organs.     

Estimation of carotenoid bioavailability from fresh stir-fried vegetables using an in vitro digestion/Caco-2 cell culture model

We previously developed an in vitro model to estimate the relative bioavailability of carotenoids from a meal prepared using commercial baby foods. The general applicability of this model was tested using a stir-fried meal consisting of fresh spinach, fresh carrots, tomato paste, and vegetable oil. After in vitro digestion of the cooked meal, the aqueous fraction was separated from residual oil droplet and solids by centrifugation to quantify micellarized carotenoids. The percentages of lutein, lycopene, α-carotene, and β-carotene transferred from the meal to the micellar fraction were 29.0 ± 0.6, 3.2 ± 0.1, 14.7 ± 0.3, and 16.0 ± 0.4, respectively. Carotenoid transfer from the meal to the aqueous fraction was inhibited when bile extract was omitted from the intestinal phase of digestion. The bioavailability of the micellarized carotenoids was validated using differentiated cultures of Caco-2 human intestinal cells. All four carotenoids were accumulated in a linear manner throughout a 6-hr incubation period. Metabolic integrity was not compromised by exposure of cultures to the diluted aqueous fraction from the digested meal. The addition of 500 μmol/L α-tocopherol to test medium significantly improved the stability of the micellar carotenoids within the tissue culture environment. These results support the utility of the in vitro digestion procedure for estimating the bioavailability of carotenoids from foods and meals.     

Phytostabilization of Amended Soils Polluted with Trace Elements Using the Mediterranean Shrub: Rosmarinus Officinalis

We evaluate the mid-term effects of two amendments and the establishment of R. officinalis on chemical and biochemical properties in a trace element contaminated soil by a mine spill and the possible use of this plant for stabilization purposes. The experiment was carried out using containers filled with trace element polluted soil, where four treatments were established: organic treatment (biosolid compost, OAR), inorganic treatment (sugar beet lime, IAR), control with plant (NAR) and control without plant (NA). Amendment addition and plant establishment contributed to restore soil chemical (pH, total organic carbon, and water soluble carbon) and biochemical properties (microbial biomass carbon and the enzymatic activities: aryl-sulphatase and protease). The presence of rosemary did not affect soluble (0.01 M CaCl₂) Cd and Zn and decreased trace element EDTA extractability in amended soils. There were no negative effects found on plant growth and nutrient content on polluted soils (NAR, OAR, and IAR). Trace element contents were within normal levels in plants. Therefore, rosemary might be a reliable option for successful phytostablization of moderate trace element contaminated soils.     

Enhancement of Oral Bioavailability of Cilostazol by Forming its Inclusion Complexes

The study was designed to investigate the effect of cyclodextrins (CDs) on the solubility, dissolution rate, and bioavailability of cilostazol by forming inclusion complexes. Natural CDs like β-CD, γ-CD, and the hydrophilic β-CD derivatives, DM-β-CD and HP-β-CD, were used to prepare inclusion complexes with cilostazol. Phase solubility study was carried out and the stability constants were calculated assuming a 1:1 stoichiometry. Solid cilostazol complexes were prepared by coprecipitation and kneading methods and compared with physical mixtures of cilostazol and cyclodextrins. Prepared inclusion complexes were characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry (DSC), and X-ray diffraction (XRD) studies. In vitro dissolution study was performed using phosphate buffer pH 6.4, distilled water, and HCl buffer pH 1.2 as dissolution medium. The optimized inclusion complex was studied for its bioavailability in rabbit and the results were compared with those of pure cilostazol and Pletoz-50. Phase solubility study showed dramatic improvement in the solubility of drug by formation of complexes, which was further increased by pH adjustment. The dissolution rate of cilostazol was markedly augmented by the complexation with DM-β-CD. DSC and XRD curves showed sharp endothermic peaks indicating the reduction in the microcrystallinity of cilostazol. Selected inclusion complex was also stable at ambient temperature up to 6 months. The in vivo study revealed that DM-β-CD increased the bioavailability of cilostazol with low variability in the absorption. Among all cilostazol–cyclodextrins complexes, cilostazol–DM-β-CD inclusion complex (1:3) prepared by coprecipitation method showed 1.53-fold and 4.11-fold increase in absorption along with 2.1-fold and 2.97-fold increase in dissolution rate in comparison with Pletoz-50 and pure cilostazol, respectively.     

Iron bioavailability from fortified fluid milk and petit suisse cheese determined by the prophylactic-preventive method

In this research, we measure the iron bioavailability of micronized ferric orthophosphate when it is used to fortify low-fat fluid milk enriched with calcium and petit suisse cheese using the prophylactic-preventive method in rats. Four groups of male weaned rats received a basal diet (control diet; 6.5 ppm Fe), a reference standard diet (SO₄Fe; 18.2 ppm Fe), a basal diet using iron-fortified fluid milk as the iron source (milk diet; Fe ppm 17.9), and a basal diet using iron-fortified petit suisse cheese as the iron source (cheese diet; 18.0 ppm Fe) for 22 d. The iron bioavailability of the different sources was calculated as the ratio between the mass of iron incorporated into hemoglobin during the experiment and the total iron intake per animal. The relative biological values with regard to the reference standard (RBV%) were 61% and 69% for the milk and cheese diet, respectively. These results show that according to this method, the iron bioavailability in both fortified foods can be considered as medium bioavailability rates.     

Effect of phytate on element bioavailability in the second generation of rats

In this paper the relation between long term consumption of a high dose of sodium phytate and the mineral status of the organism is evaluated in rats. For this purpose, element concentrations (Ca, Mg, Fe, Zn, Mn) were determined in liver, heart, testicle, bone and urine of a second generation of Wistar rats, treated with a phytate free diet (AIN-76A) and with the same diet plus 1% phytate as sodium salt. The most significant differences were observed between bone zinc contents of male and female rats. The zinc content of rats fed a 1% phytate as sodium salt diet resulted clearly lower than that found in no-phytate treated rats. Hence, it is concluded that when up to 1% of phytate as sodium salt is consumed together with an equilibrated purified diet (free of phytate), no decrease in mineral bioavailability is observed in second generation rats, except for an indication of lower zinc availability by lower zinc concentrations in some organs, mainly bone. However, using this purified diet, the zinc concentration in bone resulted around 10 times higher than found in rats fed with a common non purified rat chow.     

Formulation, Release Characteristics and Bioavailability Study of Oral Monolithic Matrix Tablets Containing Carbamazepine

This study examined the release of carbamazepine (CBZ) from hydrophobic (Compritol 888 ATO) and hydrophilic-hydrophobic matrix combination (Compritol 888 ATO-hydroxpropyl methylcellulose, HPMC). Hydrophobic matrix tablets were prepared by hot fusion technique, while hydrophilic-hydrophobic matrix tablets were prepared by wet granulation technique. The properties of the compressed matrix tablets were determined according to the US Pharmacopoeia. Both matrix formulations displayed a controlled-release profile when compared to the reference formulation (Tegretol CR 200). The bioavailability of CBZ formulations and Tegretol CR 200 were evaluated in beagle dogs. Carbamazepine presented a significant higher bioavailability from matrix tablets containing hydrophilic polymer (HPMC) than that obtained from Tegretol CR200. The average inter-subject plasma concentration variability CV% was the least with tablet containing hydrophilic polymer (HPMC) and was the highest with Tegretol CR 200 (33.8 and 54.1, respectively). Analysis of variance applied to log AUC(0-alpha) and log C(max) showed statistical significant differences among the three formulations (P < 0.05). Plotting the fraction of CBZ released in vitro and fraction absorbed showed a statistically significant relationship (R(2) = 0.935-0.975) for the three matrix tablets examined.     

Nanocrystal technology, drug delivery and clinical applications

Nanotechnology will affect our lives tremendously over the next decade in very different fields, including medicine and pharmacy. Transfer of materials into the nanodimension changes their physical properties which were used in pharmaceutics to develop a new innovative formulation principle for poorly soluble drugs: the drug nanocrystals. The drug nanocrystals do not belong to the future; the first products are already on the market. The industrially relevant production technologies, pearl milling and high pressure homogenization, are reviewed. The physics behind the drug nanocrystals and changes of their physical properties are discussed. The marketed products are presented and the special physical effects ofnanocrystals explained which are utilized in each market product. Examples of products in the development pipelines (clinical phases) are presented and the benefits for in vivo administration of drug nanocrystals are summarized in an overview.     

Does the accumulation of trace metals in crustaceans affect their ecology—the amphipod example?

Crustaceans, like all aquatic invertebrates, take up and accumulate metals from a wide range of sources and the trace metal concentrations within their tissues and bodies show great variability. Trace metal uptake in crustaceans occurs from the water and food, either of which may be affected by the physico-chemical properties of the sediment. Accumulated metal concentrations in amphipods are contrasted with those of other crustaceans and examples are given to show how external and internal factors affect bioaccumulation. One of the major pathways for the uptake of trace metals is from solution directly through permeable surfaces including the gills. Changes in salinity and oxygen tension can modify the uptake characteristics from solution particularly in the case of interstitial water within sediments. Infaunal amphipods have direct contact with the sediment and the bioavailabilities of trace metals depend on the strength of the metal binding which is determined by a combination of properties including grain size, organic content, the presence of metals such as lead and iron as well as other ambient environmental conditions. Metal concentrations within amphipod bodies reflect the bioavailabilities of trace metals in their habitat. Body size is one of the major factors contributing to individual variability in trace metal concentrations within species. For some amphipod species, there are differences in trace metal accumulation with gender, breeding and developmental stage. In amphipods, accumulated body metal concentrations are the best biomarkers for environmental metal availabilities. Metal accumulation affects the ecology of crustaceans as a consequence of the energy costs associated with excreting and/or detoxifying the incoming metals. If the costs are significant, then this may result in reduced growth and reproduction. The effects of accumulated metals on communities have yet to be determined. Accumulated metals in crustacean prey species may be transferred along the food chain, but biomagnification in fish appears unlikely. One of the main ecological challenges is the need to link molecular biomarkers with ecologically relevant life history characteristics including growth, survival, reproduction and recruitment.