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In soil, iron (Fe) solubility depends on complex interactions between Fe minerals and organic matter, but very little is known about plant availability of Fe present in Fe oxides associated with humic substances. For this purpose, this study investigates the effect of Fe mineral crystallinity in the presence of humic acids (HA) on Fe availability to plants. Four Fe–HA mineral coprecipitates were prepared, either in the presence or absence of oxygen, i.e., two goethite (G)‐HA samples containing large amounts of Fe as nanocrystalline goethite and ferrihydrite mixed phases, and two magnetite (M)‐HA samples containing crystalline magnetite. Bioavailability studies were conducted in hydroponic systems on cucumber plants (Cucumis sativus L.) grown under Fe deficient conditions and supplied with the Fe–HA coprecipitates containing goethite or magnetite. Results showed that plants grown in the presence of Fe–HA coprecipitates exhibited a complete recovery from Fe deficiency, albeit less efficiently than plants resupplied with Fe‐chelate fertilizer used as control (Fe‐diethylene triamine penta acetic acid, Fe‐DTPA). However, the supply with either G‐ or M–HA coprecipitates produced different effects on plants: G–HA‐treated plants showed a higher Fe content in leaves, while M–HA‐treated plants displayed a higher leaf biomass and SPAD (Soil–Plant Analysis Development) index recovery, as compared to Fe‐DTPA. The distribution of macronutrients in the leaves, as imaged by micro X‐ray fluorescence (µXRF) spectroscopy, was different in G–HA and M–HA‐treated plants. In particular, plants supplied with the poorly crystalline G–HA coprecipitate with a lower Fe/HA ratio showed features more similar to those of fully recovered plants (supplied with Fe‐DTPA). These results highlight the importance of mineral crystallinity of Fe–HA coprecipitates on Fe bioavailability and Fe uptake in hydroponic experiments. In addition, the present data demonstrate that cucumber plants can efficiently mobilize Fe, even from goethite and ferrihydrite mixed phases and magnetite, which are usually considered unavailable for plant nutrition.

Background CriPec technology enables the generation of drug-entrapped biodegradable core-crosslinked polymeric micelles (CCPM) with high drug loading capacity, tailorable size, and drug release kinetics. Docetaxel (DTX)-entrapped CCPM, also referred to as CPC634, have demonstrated favorable pharmacokinetics, tolerability, and enhanced tumor uptake in patients. Clinical efficacy evaluation is ongoing. CPC634 is currently stored (shelf life > 5 years) and shipped as a frozen aqueous dispersion at temperatures below -60°C, in order to prevent premature release of DTX and hydrolysis of the core-crosslinks. Consequently, like other aqueous nanomedicine formulations, CPC634 relies on cold chain supply, which is unfavorable for commercialization. Lyophilization can help to bypass this issue. Methods and results Freeze-drying methodology for CCPM was developed by employing CPC634 as a model formulation, and sucrose and trehalose as cryoprotectants. We studied the residual moisture content and reconstitution behavior of the CPC634 freeze-dried cake, as well as the size, polydispersity index, morphology, drug retention, and release kinetics of reconstituted CPC634. Subsequently, the freeze-drying methodology was validated in an industrial setting, yielding a CPC634 freeze-dried cake with a moisture content of less than 0.1 wt%. It was found that trehalose-cryoprotected CPC634 could be rapidly reconstituted in less than 5 min at room temperature. Critical quality attributes such as size, morphology, drug retention, and release kinetics of trehalose-cryoprotected freeze-dried CPC634 upon reconstitution were identical to those of non-freeze-dried CPC634. Conclusion Our findings provide proof-of-concept for the lyophilization of drug-containing CCPM and our methodology is readily translatable to large-scale manufacturing for future commercialization.

Lenticular, ellipsoidal and flat tubular hematite particles were precipitated from ferric nitrate solutions in presence of minor amounts of Al, Si, Mg and organic acids (oxalic, citric and tartaric). Particle shape identification was performed using Atomic Force Microscopy (AFM) and Transmission Electron Microscopy (TEM). Arsenate adsorption onto hematite with different morphologies was studied in batch experiments and through vibrational spectroscopy. Three bands assigned to As(V)–O–Fe at, respectively, 920, 895 and 820 cm−1 were in agreement with sorption data indicating inner-sphere complexes. As(V) adsorption kinetics was well described by a general model for diffusion into microporous surface sites showing large difference among the studied hematite samples. The maximum As(V) adsorption occurred near pH 4.0 while at alkaline pH there was a significant decrease of adsorption as confirmed by the shift of infrared As–O stretching bands of arsenate group. A change from tetrahedral Td symmetry to more stable symmetric groups such as C3v (monodentate complex), C2v (bidentate binuclear) or C1v (edge-sharing, bidentate binuclear) was deduced for As(V) sorbed on hematite. Fast arsenate adsorption was higher on ellipsoidal hematite particle with a dominant non basal (1 1 0) face. On the contrary, electrostatic attraction interaction could explain the fast As(V) adsorption on platy morphology characterized by basal face (0 0 1). Despite the discrepancy between theoretical considerations and experimental observations, the present contribution could lead to better understanding of the role played by hematite morphology on surface complexation model to describe arsenic adsorption behavior. Diffusional mass transport models applied to As sorption systems can explain such divergence due to: (i) external mass transport across the boundary layer surrounding the particle; (ii) diffusional mass transfer within the internal structure of the adsorbent particle by a nanopore, (iii) heterogeneity of the surface site. These findings are relevant to understanding the rates of interfacial processes involving arsenate sorption that can be take into account in mass transport models used for the removal of arsenic from contaminated water or wastewaters.

In marginal rural areas, intensification and mechanization of agriculture have determined changes in farming systems, which can increase soil erosion and reduce soil quality and carbon stock. Low input farming systems are alternative to conventional ones. The study aims to gain some insights in the composition of TOC in calcaric soils (Leptic Calcisols) and (Luvic Phaezem) using Vis-NIR reflectance spectroscopy in combination with partial least squares regression (PLSR). Secondary objectives were defining the most appropriate pre-processing techniques of Vis-NIR reflectance spectra, and predicting TOC in calcaric soils. The study area was located at Montecorvino Rovella (Salerno, southwestern Italy), characterized by an olive grove. Univariate PLSR analyses were performed using as response variables either TOC or total carbonate content and as predictors pH, electrical conductivity (EC) and absorbance spectra. The best results were obtained using as spectral data pre-treatments standard normal variate and Savitzky-Golay polynomials with the first derivative. Variable Importance for Prediction (VIP) statistics showed to be a good tool to gain insights in TOC composition also when its content is low and influenced by carbonate.

Minimizing nitrification of fertilizer ammonium (NH4+) can reduce nitrate (NO3−) contamination of groundwater and increase nitrogen (N) use efficiency (NUE). Olive mill wastewater (OMW), hydroalcoholic extracts of Mentha piperita L. (Mp) and Artemisia annua L. (Aa), and synthetic nitrification inhibitor (NI) dicyandiamide (DCD) were investigated. All NIs reduced activity of nitrifying bacteria and NO3− leached and increased efficiency of N metabolism of celery (Apium graveolens L.) during 56 days in a soil mixture fertilized with ammonium sulfate [(NH4)2SO4]. Soil NO3− leaching losses of DCD, OMW, Mp, and Aa treatments were 24%, 26%, 67%, and 78% of the untreated control loss, respectively, at 35 and 56 days after planting (DAP). Decreased nitrification by NIs resulted in greater concentrations of soil NH4+ correlated with less nitrate reductase (NR) activity in roots and leaves and less soil acidification compared to the control. At 35 and 56 DAP, DCD and OMW treatments decreased NR and increased glutamine synthetase activities in leaves and roots, compared to the control. NIs increased leaf and root protein and amino acids. OMW significantly decreased leaching loss of NO3− to 10% of fertilizer N applied to the soil, compared to 38% of applied NH4+-N leached from the control. OMW proved an effective alternative to DCD to improve NUE of NH4+-fertilizers.

Magnetite nanoparticles (NPs) were synthetized by partial oxidation of hot Fe(II) sulfate aqueous solutions upon addition of variable amounts of alkali/nitrate ions in a N2 atmosphere. The resulting NPs were extensively characterized by Scanning Electron Microscopy (SEM), X-Ray Powder Diffraction (XRPD), Dynamic Light Scattering (DLS) and Brunauer-Emmett-Teller (BET) analysis. Depending on the final pH after synthesis, partially oxidized magnetite NPs were obtained with average crystallite size ranging from 29 to 116 nm. The potential of NPs as arsenic adsorbents was investigated through batch adsorption experiments. The analysis of the adsorption isotherms performed on the basis of both Freundlich and Langmuir models, revealed that arsenic adsorption capacity was more efficient for magnetite NPs synthetized at final pH ≤ 6.56, characterized by polydisperse submicrometric aggregates with coarse macro- and mesopore distributions.

The iron (Fe) oxide particles affect a wide range of important environmental processes related to soil fertility and plant growth. They often occur as aggregates, mineral nanoparticles or as nanoscale coatings on other grains in the soil, where they may also control the fate and transport of nutrients such as phosphate, sulfate, molybdate and pollutants (arsenic or chromium). Solubilization of Fe from minerals control iron availability for plant growth; this process is regulated by chemical mechanisms (pH and dissolution-precipitation), sometimes mediated by biological interactions at rhizosphere scale, of both Fe crystalline and poorly ordered Fe oxide minerals. In cold and temperate climate the organic carbon storage and the Fe minerals are highly correlated, possibly because the interactions of nano-size iron oxide particles with humic substances. The aims of this review are to summarize the main findings and the classical iron soil chemistry and to propose chemical and biological relationships with the hope of stimulating new model in soil fertility.

Polymer nanoparticles (NPs) have recently attracted increasing attention and represent one of the main and important novelties in nanomedicine. In particular, they exhibit several advantages like the ability to tailor and sustain the release of hydrophobic drugs, high biocompatibility and degradability, together with the possibility to be highly cell selective. However, the usage of NPs in several diseases can be limited by their route of administration: in fact their diffuse distribution in tissues and organs does not allow to address them specifically in the target situ limiting therapeutic outcome and increasing potential side effects. In this work we studied the self-assembly of opposite charged polymer nanoparticles able to retain aqueous solutions, with the aim of creating self-assembled macrostructures that can release both hydrophobic and hydrophilic compounds. NPs were synthesized with a two-steps process starting from e-caprolactone and hydroxyethyl methacrylate to create biodegradable macromonomers which were then co-polymerized in an emulsion polymerization with methacrylic acid and either a positive charged surfmer (HEMA-Ch + ) or a negative one (HEMA-SO 3 − ). The feasibility to assemble these NPs into macrostructures was studied and the structures of the final products as well as their ability to release mimetic drugs were evaluated.

The production of porous clusters by controlled aggregation of polyacrylonitrile nanoparticles and thermal treatment and their application to CO2 capture were explored. The synthesis of the primary particles by emulsion polymerization showed good reproducibility and easy scale up. The following gelation of the produced latexes (controlled destabilization by salt addition) resulted in the formation of macroporous monoliths of nanoparticles with mean pore diameter of 100 nm. A carefully assessed thermal treatment was then applied to the dried monolith after grinding. The produced porous clusters were processed through three high-temperature steps: oxidation, stabilization and pyrolysis. The latter permits the creation of micropores in the initially non-porous nanoparticles, thus enabling the access to the remaining nitrogen-bearing species present in the pyrolyzed polymer. The relative contributions of the remaining nitrogen-bearing species and of the micropores were elucidated by applying different oxidation temperatures. In particular, the fraction of the pores with diameter smaller than 0.7 nm was decisive to determine the final capture ability. After a treatment including oxidation at 240 °C, stabilization at 350 °C and pyrolysis at 900 °C, the best reported material showed an average CO2 adsorption capacity of 3.56 ± 0.17 mol(CO2)/kg at 0 °C and 1 atm.

The aim of this study was to verify the significance of land use on nitrate availability (NO 3 –N) at landscape scale in two different sites by using multivariate geostatistical methods. NO 3 –N and several other soil properties of Nitrate Vulnerable Zone (NVZ) monitoring network of 71 and 63 top-soils, respectively were measured in Venafro and Campomarino areas of Southern Italy (Molise region). Data analysis was performed firstly with classical descriptive statistics assuming spatial independence of samples; secondly, geostatistical analysis was performed in order to investigate spatial dependence and estimate map soil indices. The result of the distribution of NO 3 –N contents indicates the existence of many hot spots (high kurtosis) with high NO 3 –N concentration in both the study areas. Higher NO 3 –N levels in Venafro were distributed in the central zone that appeared to be correlated with animal manure applied to the fields in the summer strongly associated to high values of soil organic matter (SOM) and total nitrogen (Ntot). In Campomarino, the highest NO 3 –N concentrations occurred in random spots that appeared lesser correlated with high SOM content and low C/N ratio. Factor co-kriging analysis was applied separately to the two data sets to synthesize the complex multivariate variation of the two areas in a restricted number of zones so they could be ranked as at different risks of NO 3 –N leaching. The loading values of the factors indicate that Venafro SOM and clay and, to a lesser extent, Ntot and C/N are the variables that mainly affect the first factor at shorter range. On the other hand, cation exchangeable capacity (CEC) and, to a less extent, silt, SOM, C/N and fine sand content weighed more, but negatively, on the first factor at longer range. For Campomarino, clay content and available water capacity (AWC) and, to a lesser extent, NO 3 –N, weighed more and positively on the first factor at shorter range. The first factor at longer range was quite exclusively dominated by elevation and partially and negatively by pH and CaCO 3 . Soil factor map appears more variable in both the NVZ areas, characterized by many spots indicative of intensive land use and management. The highest NO 3 –N levels were found in intensive land use and in dairy farming located for the most part in Venafro catchment. The maps of the two factors at small scale for Campomarino appear to be quite erratic owing to the small size of the farms with different cropping systems differently managed. The results, of the present research, provide data useful to support land use planning and soil management, to mitigate soil nitrate leaching. Reduction in soil NO 3 –N could be achieved by enhancing useful recommendations in N fertilization and animal manure application to farmers.

Heavy metals provoke environmental pollution with potentially toxic effects on human and plants systems. Recently, investigations are conducted on plants that may play a relevant role on pollutants absorption or stabilization, focusing on fast growing tree species in agronomic conditions; little is known on the effects of contaminants on tree species colonizing abandoned fields to be used in restoration ecology. The effects of Cd on photosynthetic performance and metal accumulation were investigated in Quercus pubescens Willd. seedlings grown in pots containing a mixture of sand, clay, turf and Cd-treatments (0, 25 and 75 mg kg-1 dry soil). The studied photosynthetic parameters (Asat= net phytosynthesis; Rday= day respiration; Γcomp= CO2 compensation point; Vcmax= maximum carboxylation rate; Jmax = electron transport rate; TPU = triose phosphate use; Ci/Ca = ratio of intercellular (Ci) to ambient (Ca) [CO2] (Ci/Ca); Jmax/Vcmax = ratio; (gsmax) = maximum stomatal conductance; (lg) = stomatal conductance estimated relative to the photosynthetic rate; (Fv/Fm) = maximum quantum yield of PSII photochemistry; (ΔF/F’m) = effective photochemical efficiency) varied progressively with increasing Cd concentration in the soil, highlighting a negative impact on photosynthetic potential and PSII functioning. Approximately 10% of added Cd was found to be extractable from the substrate, at the maximum concentration applied, with about 12 and 0.75 as bioaccumulation and translocation factors, respectively. Analogously, Cd accumulated up to 34, 30 and 46 mg kg-1 in leaves, stem and roots, respectively. While it is not possible to extrapolate from the present study with seedlings to effects on mature pine trees, there are clear implications for regeneration in soils contaminated with heavy metals, which may lead to ecosystem deterioration.

Background Statins enhance the synthesis of long-chain polyunsaturated fatty acids (LC-PUFAs) from their precursors both in vitro and in vivo. In particular, an increased conversion of linoleic acid (LA) and of alpha-linolenic acid to their derivatives is observed in cultured cells. On the contrary, cigarette smoke (CS) negatively and dose-dependently affects the LC-PUFA production. Aim To evaluate the effects of CS alone or with simvastatin, on [1- 14 C] LA metabolism in THP-1 cells. Results CS inhibits LA conversion; after co-incubation, simvastatin nullifies the effects of CS, maintaining LA conversion comparable to controls. However, at the highest CS concentration, simvastatin is unable to counteract the effects of CS. Changes of LA conversion reflect the modulation of desaturase activities by simvastatin and CS. Conclusion CS decreases PUFA conversion and its effects are modulated by the opposite effect of statins. It can be speculated that statin treatments in smoking patients may provide some beneficial effects on PUFA metabolism in addition to lowering cholesterol levels.

Background and aims Ingestion of alpha linolenic acid (ALA), with the richest source among dry fruits such as walnuts, is associated with cardiovascular prevention. The aim of this study was to selectively evaluate the effects of moderate walnut consumption on the levels of ALA and its metabolic derivatives in human blood. Methods and results After a 2-week run-in period, 10 volunteers consumed 4 walnuts per day (in addition to their habitual diet) for 3 weeks. Fatty acid profiles, with special attention to levels of ALA and long chain polyunsaturated fatty acids (LC-PUFA), were assessed in blood drops collected from fingertips. The data indicate that the administration of a few walnuts a day for 3 weeks significantly increases blood levels, not only of ALA (from 0.23 ± 0.07 SD to 0.47 ± 0.13 SD), but also of its longer chain derivative eicosapentaenoic acids (EPA) (from 0.23 ± 0.37 to 0.82 ± 0.41) with levels remaining elevated over basal values after washout. Conclusion The findings of this pilot study indicate that plant ALA in appropriate food items favourably affects the n-3 LC-PUFA status.

Polymer nanoparticles (NPs) represent a promising way to deliver poorly water-soluble anticancer drugs without the use of unwanted excipients, whose presence can be the cause of severe side effects. In this work, a Cremophor-free formulation for paclitaxel (PTX) has been developed by employing PEGylated polymer nanoparticles (NPs) as drug delivery carriers based on modified poly(Ε-caprolactone) macromonomers and synthesized through free radical emulsion polymerization. Paclitaxel was loaded in the NPs in a postsynthesis process which allowed to obtain a drug concentration suitable for in vivo use. In vivo experiments on drug biodistribution and therapeutic efficacy show comparable behavior between the NPs and the Cremophor formulation, also showing good tolerability of the new formulation proposed.

In this work, ring-opening polymerization and reversible addition-fragmentation chain transfer polymerization (RAFT) have been employed for the production of block copolymers where the backbone is brushed with poly(ethylene glycol) (PEG) and polyester chains. Because of their amphiphilic properties, they are able to self-assemble in water, forming micelles. Molecular dynamics simulations have been accomplished to study the behavior of the copolymer single chain in water, and the self-assembly properties have been characterized and correlated to the copolymer structure in terms of critical micellar concentration and particle size. As a proof of their flexibility, these materials have been employed for the production of polymer–lipid hybrid nanoparticles with tunable dimensions (from 120 to 260 nm) adopted for the controlled release of anticancer compounds (paclitaxel and curcumin). © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43084.

In THP-1 cells, simvastatin decreases, in a concentration-dependent manner, cholesterol synthesis and increases linoleic acid (LA) conversion to its long-chain derivatives, in particular to arachidonic acid, activating delta6 and delta5 fatty acid (FA) desaturases. The intermediates in cholesterol synthesis, mevalonate and geranylgeraniol, partially reverse the effects of simvastatin on the LA conversion. The aims of this work were to evaluate: (i) the correlation between cholesterol synthesis and desaturase activity and (ii) the possible involvement of protein isoprenylation in desaturase activity, assessed through pharmacological treatments. THP-1 cells were incubated with [1-14C]LA or with [1-14C]di-homo-gamma-linolenic acid (DHGLA) and treated with simvastatin or with curcumin and nicardipine, inhibitors of desaturases. Curcumin was more active than nicardipine in inhibiting LA and DHGLA conversion: 20 microM curcumin, alone or with simvastatin, totally inhibited delta6 and delta5 desaturation steps; 10 microM nicardipine only partially inhibited the enzymes, being more active on delta5 desaturase. Simvastatin treatment decreased the incorporation of acetate in cholesterol (-93.8%) and cholesterol esters (-70.2%), as expected. Curcumin and nicardipine also decreased cholesterol synthesis and potentiated simvastatin. Finally, the isoprenylation inhibitors (perillic acid and GGTI-286) neither affected the conversion of LA nor inhibited the delta5 desaturase activity. In conclusion, our results indicate that there is no direct relationship between cholesterol synthesis and desaturase activity. In fact, simvastatin decreased cholesterol synthesis and enhanced LA conversion (mainly delta5 desaturation), whereas curcumin and nicardipin decreased delta5 desaturation, with a limited effect on cholesterol synthesis.

Goethite and lepidocrocite are considered the stable species of Fe oxyhydroxides formed from Fe2 + oxidation in mildly acidic soil environments, while maghemite is formed in mildly alkaline conditions. Complexing ligands, especially humic acid (HA), can change the pathway formation of these iron oxyhydroxides from Fe2 + oxidation. This research aimed to assess the influence of HA on Fe2 + oxidation and its effect on crystalline Fe mineral products. Ferrous iron was added to HA at increasing initial COOH/Fe(II) charge ratios (R) at pHs of 5.0 and 8.0 and aged at 70 °C for 1 month and up to 8 years at room temperature. The precipitated products after aging were analysed using XRD, FT-IR, TEM and AFM. The results indicate that oxidation of Fe2 + at pH 5.0, in the presence of large amounts of HA (R = 0.1) promoted the formation of goethite together with ferrihydrite. Oxidation of Fe2 + in slightly alkaline conditions (pH 8.0) yielded maghemite with small amounts of goethite. Further, long-term aging of HA coprecipitated with Fe2 + perturbed the stacking of the Fe hydroxyl sheets at pH 5.0, favouring the formation of ferrihydrite. At pH 8.0 the presence of humic acid does not influence the crystallinity of the precipitation products and maghemite was still stable after 8 years of aging. This research confirms that the oxidation of Fe2 + in soil and its subsequent hydrolysis is a very common process of Fe hydroxides/oxide formation in acidic soil environments. The type of Fe oxide formed depends strictly on the pH and secondly on the rate of oxidation, especially on the presence and amount of organic compounds that inhibit crystal growth. Humic acid are the main organic molecules in soils, particularly in cool, humid weathering environments where they lead to a decrease in crystalline perfection and promote the formation of ferrihydrite instead of goethite or lepidocrocite. These results provide significant insights into the effect of the mobility of HA in association with Fe minerals.

One of the major drawbacks that limits the clinical application of nanoparticles is the lack of preliminary investigations related to their biocompatibility, biodegradability and biodistribution. In this work, biodegradable PEGylated polymer nanoparticles (NPs) have been synthesized by using macromonomers based on poly(ε-caprolaconte) oligomers. More in detail, NPs have been produced by adopting a surfactant-free semibatch emulsion polymerization process using PEG chains as a stabilizing agent. The NPs were also labeled with rhodamine B covalently bound to the NPs to quantitatively study their biodistribution in vivo. NPs were investigated in both in vitro and in vivo preclinical systems to study their biodistribution in mice bearing B16/F10 melanoma, as well as their biocompatibility and biodegradability. The NP concentration was evaluated in different tissues at several times after intravenous injection. The disappearance of the NPs from the plasma was biphasic, with distribution and elimination half-lives of 30 min and 15 h, respectively. NPs were retained in tumors and in filter organs for a long time, were still detectable after 7 d and maintained a steady concentration in the tumor for 120 h. 48 h after injection, 70± 15% of the inoculated NPs were excreted in the feces. The favorable tumor uptake, fast excretion and absence of cytotoxicity foster the further development of produced NPs as drug delivery carriers. © 2014 IOP Publishing Ltd.

A study was carried out to examine the competition in adsorption of sulfate (SO4) and oxalate (OX) on goethite as affected by pH, concentration of the ligands, order of anion addition, and the presence of phosphate (PO4). The purpose was to obtain useful information about the factors that influence

Hepatic lipid metabolism is extremely modified by excessive ethanol consumption, but the cellular mechanisms of such alterations are still largely unexplored. S-Adenosyl-L-methionine (SAMe) is known as an important methylating agent and as a precursor of glutathione and it has been shown to prevent some of the toxic effects of ethanol in the liver. We therefore studied the effects of ethanol on cholesterol synthesis in a human hepatomal cell line (HepG2), the kinetics of SAMe, and its putative protective effects on the alterations of lipid metabolism induced by toxic concentrations of alcohol. Incubation of HepG2 cells with [3H]SAMe resulted in a progressive increase in the labelling of phosphatidylcholine and of its two intermediates during synthesis starting from phosphatidylethanolamine. This process is enzymatic, since it does not take place in heat-inactivated cells. Also, ethanol induced an increase in cholesterol and triglycerides syntheses and a decrease in phospholipid labelling. These alterations were not prevented by SAMe 10(-4) M, indicating that the protective effects of the drug are related to other mechanisms of action such as reduced formation of collagen, restoration of glutathione levels, and normalization of membrane functions.

In this work a large number of polymer nanoparticles (NPs) with different features have been synthesized through emulsion polymerization-based methods. Poly(methyl methacrylate) (PMMA), poly-ɛ-caprolactone (PCL), and poly(lactic acid) (PLA) based NPs with different size, hydrophobicity, surface charge, PEGylation degree, type of emulsifier and ζ potential have been produced and characterized. All the different NPs have been adopted for cellular uptake studies, leading to a precise quantification of the number of internalized NPs into a selected tumor cell line. The experiments summarize, emphasize and improve the comprehension of the influence of NPs features on the uptake efficiency. In detail, a linear relationship between uptake and both size and NP concentration independently upon other NP characteristics was found. Moreover, it was confirmed that cells are able to internalize and retain for a long time preferentially positively charged NPs. Finally, by coupling results of uptake studies with cell viability measurements, an easy and fast check to control the effectiveness of a selected polymer as drug carrier has been proposed. In particular, we observed that biodegradable PLA-based NPs with high molecular weight, non-PEGylated and positively charged PCL NPs are the better choice to maximize the uptake and minimize side effect against cells.

Humic acids (HA) have a colloidal character whose size and negative charge are strictly dependent on surface functional groups. They are able to complex large amount of poorly ordered iron (hydr)oxides in soil as a function of pH and other environmental conditions. Accordingly, with the present study we intend to assess the colloidal properties of Fe(II) coprecipitated with humic acids (HA) and their effect on Fe hydroxide crystallinity under abiotic oxidation and order of addition of both Fe(II) and HA. TEM, XRD and DRS experiments showed that Fe-HA consisted of Ferrihydrite with important structural variations. DLS data of Fe-HA at acidic pH showed a bimodal size distribution, while at very low pH a slow aggregation process was observed. Electrophoretic zeta-potential measurements revealed a negative surface charge for Fe-HA macromolecules, providing a strong electrostatic barrier against aggregation. Under alkaline conditions HA chains swelled, which resulted in an enhanced stabilization of the colloid particles. The increasing of zeta potential and size of the Fe-HA macromolecules, reflects a linear dependence of both with pH. The increase in the size and negative charge of the Fe-HA precipitate seems to be more affected by the ionization of the phenolic acid groups, than by the carboxylic acid groups. The main cause of negative charge generation of Fe/HA is due to increased dissociation of phenolic groups in more expanded structure. The increased net negative surface potential induced by coprecipitation with Ferrihydrite and the correspondent changes in configuration of the HA could trigger the inter-particle aggregation with the formation of new negative surface. The Fe-HA coprecipitation can reduce electrosteric repulsive forces, which in turn may inhibit the aggregation process at different pH. Therefore, coprecipitation of Ferrihydrite would be expected to play an important role in the carbon stabilization and persistence not only in organic soils, but also in waters containing dissolved organic matter.

In the monocytic THP-1 cells, the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor simvastatin (5 microM) enhances the conversion of exogenous linoleic (18:2 n-6) and eicosapentaenoic (20:5 n-3) acids to their long-chain polyunsaturated fatty acid (LC-PUFA) derivatives, and this effect is associated with changes in the desaturation steps. In addition, formation of monounsaturated fatty acids from endogenously synthesized precursors is increased. These metabolic changes lead to elevated LC-PUFA and fatty acid (FA) unsaturation in cells. The effects of simvastatin on FA metabolism are associated with increased synthesis of triglycerides from glycerol. The dose-effect relationships for the activity of simvastatin on total linoleic acid (LA) conversion and cholesterol synthesis reveal that enhancement of PUFA metabolism is already maximal at 0.5 microM simvastatin, whereas cholesterol synthesis is further inhibited by concentrations of simvastatin up to 5 microM. The effects of 5 microM simvastatin on PUFA metabolism are partially prevented by mevalonate (1 mM) and geranylgeraniol (5 microM) but not by farnesol (10 microM). These data indicate that HMG-CoA inhibitors have profound effects on PUFA metabolism, and that the pathways for cholesterol and PUFA synthesis are mutually modulated.

Mixed hydroxy Al-Fe-montmorillonite complexes (5 mmol of Al+Fe per g of clay) were prepared at pH 5.0 by mixing different amounts of Al(NO3)3 and Fe(NO3)3 to give initial Fe/Al molar ratios (R) of 0, 0.1, 0.25, 0.5, 1.0, 4.0, 10.0 or ∞. The effect of ageing on the interlayering, mineralogy, chemical composition, CEC and external surface area of the complexes was studied. The degree of interlayering of freshly prepared and aged complexes (up to 120 days at 50°C) was always greater in the samples with R ranging from 0.5 to 4. Gibbsite and hematite (with traces of goethite) formed in the samples with R ⩽ 1 and R∞, respectively. No crystalline Fe oxide was detected by XRD analyses in the complexes with R ranging from 0.1 to 10, whereas no crystalline Al and Fe oxides were formed in the complexes at R = 4–10. However, some evidence suggests the possible formation of a microcrystalline Fe oxide/oxyhydroxide undetectable by XRD analyses in the complexes richer in Fe. The CEC and the surface area of the freshly prepared mixed hydroxy Al-Fe-montmorillonite complexes increased with increasing R. Large quantities of Al+Fe were solubilized by oxalate in the complexes with R ⩾ 0.5, even after ageing for 120 days at 50°C, indicating that interlayering of Al-Fe species at certain Fe/Al molar ratios was particularly stable.

We studied the influence of time ageing (up to 120 d at 50°C or 30d at 95°C) on the mineralogical and chemical composition of hydrolytic species of mixed aluminum and iron samples formed at pH 5.0 and initial Fe/Al molar ratio (Ri) ranging from 0.1 to 10. The partitioning distribution of Fe and Al in soluble or solid phases of different sizes ( 0.2 μm) depended on Ri and time. The ratio of Fe to Al of the 0.2 μm sizes. Gibbsite, without the presence of well-crystallized Fe-oxides was formed in the samples at Ri ≤ 0.5 after 7–120 d at 50°C. In the samples at Ri ≥ 1 low-crystalline ferrihydrite was observed after ≥60 d. Only after 120 d did gibbsite or hematite start to form in the samples at Ri = 1–10. However, even after prolonged ageing at 95°C, low-crystalline ferrihydrite was still present at Ri ≤ 4. The Fe-Al samples at Ri ≥ 1 aged 32 d at 50°C dissolved almost completely by acid ammonium-oxalate (82–93%), but the samples at Ri ≤ 0.5 were only partially solubilized (13–60%). After further 30 d at 95°C, the percentages of Fe + Al solubilized by oxalate from the samples at R ≥ 0.5 was still relatively high (22–39%).

A delivery system based on polymer nanoparticles (NPs) is developed and tested in relevant biological conditions for breast cancer treatment. ɛ-Caprolactone (CL) and polyethylene glycol (PEG) copolymers have been used for the one pot synthesis of surfactant free PEGylated NPs which are monodispersed, stable in physiological conditions and have size in the range 90-250 nm. The degradation behavior of these NPs has been investigated in cell medium and a relation between degradation time and molecular weight of the starting CL-based material has been established. This allows producing NPs with controlled degradation kinetics. Finally, selected NPs have been tested in 4T1 breast cancer cells to check their toxicity and to investigate the uptake process, in order to validate their use as targeted vectors for breast cancer treatment.

Summary: in this work the cytotoxicity of PMMA-based nanoparticles against mouse mammary cancer cells (4T1) has been investigated. NPs have been synthesized using either monomer starved semi-batch emulsion polymerization (MSSEP) or standard batch emulsion polymerization (BEP) processes adopting potassium persulfate (KPS) as initiator and two different emulsifiers: sodium dodecyl sulfate (SDS) and Tween 80. The toxicity of NPs produced using SDS has been confirmed in in vitro experiments while it has been found that NPs stabilized with Tween 80 show a good biocompatibility. Moreover, the absence of toxicity of NPs in which the SDS is substituted with Tween 80 adopting ion exchange resins (IER) has been proved. Finally the biocompatibility of the sulfate chain end groups coming from the adopted initiator has been assessed.

In vivo studies of LDL oxidation following consumption of natural phenolic compounds have yielded mixed results. It is reported that the amphiphilic hydroxytyrosol, after addition to human plasma, does not accumulate in LDL but protects plasma lipids, which are extracted together with hydroxytyrosol, from chemically-induced oxidation. Thus, a novel methodology was proposed, which does not rely on LDL separation and subsequent oxidation but is based on the oxidation of total lipids - simultaneously extracted from plasma with antioxidants - to evaluate the effects of micronutrients that do not partition into LDL, after in vivo supplementation.

The effects of different concentrations of exogenous platelet-activating factor (PAF) on the formation of arachidonic acid-cyclooxygenase metabolites and on the production of inositol phosphates have been investigated in a primary culture of rat astroglial cells. The cells were used at confluence and the purity was checked by immunostaining of the culture with specific antibodies against glial fibrillary acidic protein. Incubation of the cells with PAF (range 10(-9) to 10(-6) M) resulted in maximal accumulation of total inositol phosphate (620 +/- 60% increment over basal values, P0.001) at the concentration of 10(-8) M, after 1 min of stimulation. Smaller inositol phosphate accumulation occurred at higher concentrations of the agonist and at longer stimulation time. After 1 min of stimulation with PAF, the accumulation of the cyclooxygenase metabolites, thromboxane B2 (630 +/- 58 vs 20 +/- 2 pg/mg protein in non-stimulated samples) and 6-keto-prostaglandin F1 alpha (132 +/- 15 vs 55 +/- 7 pg/mg protein in non-stimulated samples) was also maximal at 10(-8) M concentration of the agonist. When the cultures were stimulated with PAF or Ca(2+)-ionophore after preincubation with equimolar concentration of the PAF inhibitor BN 52021, a significant inhibition in the synthesis of both inositol phosphates and cyclooxygenase metabolites occurred only in the PAF-stimulated cells.

Soil spectra, either from bi-directional reflectance (BDRS) and diffuse reflectance spectroscopy (DRS), enable the detection of small amount of hematite and goethite across the VIS-NIR region that provides information regarding the iron oxide minerals content. Good relations between the spectral parameter useful in understanding in iron oxides contents was observed with bi-directional reflectance (BDRS) and diffuse reflectance spectroscopy (DRS) of strongly and moderate weathered soils. Studied soils were Terra Rossa from Mediterranean area derived from karstic dolomitic calcareous environment and a large variety of Oxisols derived from different parent materials ranging from lateritic sediments to basaltic and calcareous rocks from Brazil. The spectra of soil samples were recorded in the laboratory on air-dried-sieved soils. The two different spectra were parameterized by using the amplitude of selected bands in the second derivative of the spectrum of the Kubelka–Munk function and by calculating the Munsell color attributes. Hematite and goethite shown very clearly band positions and second-derivative is more sensitive in detecting these two Fe oxides than Munsell color attributes. Significant correlations were found between the spectral and color parameters calculated from the two different spectra. Irrespective of the method, soil goethite and hematite contents were significantly correlated with the amplitudes of the characteristic second-derivative spectral bands at ∼ 420 and ∼ 535 nm, respectively. The hematite content was correlated with some of the Munsell color parameters, whereas the goethite content was not. Our results suggest that laboratory bi-directional reflectance spectroscopy is as useful as diffuse reflectance spectroscopy to characterize soil Fe oxides. Future work can potentially involve the execution of field-level studies employing a portable spectroradiometer to estimate soil Fe oxides composition. This result supports also the utilization of a sensitive airborne hyperspectral sensor to rapidly and quantitatively evaluate spatial soil information concerning iron oxides content.

Summary Thirteen samples from six Terra Rossa profiles of southern Italy were studied to determine the influence of Fe oxides in aggregation. Removal of all the Fe oxides by the citrate-bicarbonate-dithionite treatment resulted, in all samples, in a decrease in the proportion of the silt plus sand fraction and an increase in the clay fraction. The change in the particle size distribution (PSD) was highly correlated with the total Fe oxide content and with the hematite content but not so well correlated with the goethite content. When the samples were treated with acid NH4-oxalate to remove the poorly crystalline Fe oxides, there was a decrease in the proportion of the sand fraction and, in general, an increase in the proportion of silt and little or no increase in the proportion of clay; the change in PSD was better correlated with the ratio oxalate-extractable Si/oxalate-extractable Fe than with any other single property. This indicates that silica may contribute to aggregation, probably by forming bridges between Fe oxides and other soil particles.

Phosphate sorption and desorption in soils are markedly influenced by iron oxides, although little is known on how the common iron oxides differ in their behaviour towards added phosphate. In this study, we investigated phosphate sorption and desorption in the clay fractions of 12 Terre Rosse that ranged widely in Fe oxide content, had very low contents of oxalate-extractable Fe oxides and different hematite/goethite ratios. Phosphate sorption at an equilibrium concentration of 1 mg P 1−1 was correlated with the goethite but not with the hematite content of the clay fractions. When phosphate was desorbed by electro-ultrafiltration, the difference in desorption half-time between untreated and deferrified clays was positively correlated with the goethite but not with the hematite content. These results suggest that goethite is more active than hematite in phosphate sorption and retention by soils. Einflus von Goethit und Hamatit auf die Phosphat-Sorption und -Desorption in Terre Rosse In Boden werden Phosphat-Sorption und -Desorption von den Eisenoxiden beeinflust; der spezifische Einflus der verschiedenen Eisenoxide ist jedoch kaum bekannt. Es wurden P-Sorption und -Desorption der Tonfraktionen von 12 Terre Rosse mit sehr verschiedenen Gehalten an Goethit und Hamatit und geringem oxalat-loslichen Fe untersucht. Bei einer Gleichgewichtskonzentration von 1 mg P 1−1 war die P-Sorption mit dem Goethitgehalt, nicht dagegen mit dem Hamatitgehalt, korreliert. Die Zeit bei der durch Elektro-Ultrafiltration die Halfte des sorbierten P desorbiert wurde, war ebenfalls mit dem Goethitgehalt korreliert. Es wird gefolgert, das Goethit die P-Sorption und -Desorption dieser Boden starker beeinflust als Hamatit.

Infants in developing countries require early dietary interventions to prevent nutritional deficiencies, above all protein, energy, iron and zinc. To what extent these interventions may affect the fatty acid (FA) status is still unknown.To examine and compare the effects of 2 micronutrient "sprinkles" supplementations (iron 12.5 mg + folic acid 150 microg, iron/folate and iron 12.5 mg + folic acid 150 microg + zinc 5 mg + vitamins A, C and D3, mineral/micronutrient [MMN]) versus placebo on the FA status of Cambodian infants.A total of 204 infants age 6 mo and living in Kompong Chhnang Province, Cambodia, were randomly assigned to receive daily supplementation of MMN (n = 68) and iron/folate (n = 68) or placebo (n = 68) for a 12-mo period in powder form as sprinkles. At the end of the intervention period, FAs in the range of 16 to 24 C were determined in blood drops absorbed on a strip collected from 182 subjects, and values among the 3 intervention subgroups and those of 21 Italian 18-mo-old, normal-growing infants as the reference group were compared.At the end of the supplementation trial, higher levels of the 2 essential FAs (EFAs) (linoleic acid, 18:2n-6, and alpha-linolenic acid, 18:3n-3) were found in the MMN group. No differences occurred for the major longer chain derivatives of both EFAs arachidonic acid (20:4n-6) and docosahexaenoic acid (22:6n-3). In MMN supplemented Cambodians, blood levels of linoleic acid approached those of Italian infants, and in addition their alpha-linolenic acid levels were improved. Cambodian infants, mostly still breast-fed through the second year of life, showed significantly higher levels of long-chain derivatives of both the n-6 and the n-3 series compared with Italians.Supplementation with iron, folic acid, zinc and vitamins was associated with an increase of linoleic acid and alpha-linolenic acid levels in Cambodian infants versus placebo, without significant changes in the concentrations of their longer chain derivatives, resulting in a FA status closer to Italian counterparts for the essential polyunsaturated FA levels. The iron/folate-treated infants showed no differences compared with the other 2 groups. Studies are needed to differentiate the potential effects of the supplemented micronutrients on the FA status.

The equilibrium adsorption and binding of DNA from Bacillus subtilis on complexes of montmorillonite-humic acids Al or Fe hydroxypolymers (Al-M-HA or Fe-M-HA) at different M/HA ratios, the desorption of DNA, the capacity of bound DNA to transform competent cells of B. subtilis in vitro, and the protection of bound DNA from degradation by free and organomineral-bound DNase I are reported. Adsorption was rapid (maximal after 2 h), occurred from pH 3 to 10, and was higher on Al-M-HA than on Fe-M-HA. Saturation of the sites on the surface or between the layers of Al- or Fe-M-HA occurred with only some complexes, depending on how the complexes were prepared. Essentially no desorption under stringent conditions was observed. Bound DNA transformed auxotrophic competent cells of B. subtilis, although at a lower frequency than free DNA. Bound DNA was protected more than free DNA against degradation by DNase I, and differences in resistance to degradation between free and bound DNA were more evident when DNase was also bound on the organomineral complexes.

The aim of this work was to study the influence of tannate concentration (tannic acid/Al molar ratio [R] of 0.01–0.1), pH (5.0 and 8.0), order of aluminum, hydroxyl, and tannate addition, and prolonged ageing at different temperatures (10 months at 50°C and 5 y at room temperature and further ageing for 3–15 days at 140°C) on the nature and crystallinity of synthetic boehmite. Tannate facilitated the formation of boehmite relative to Al(OH)3 polymorphs when coprecipitated with Al and also when added to Al(OH)x phases already formed at pH 4.5 or 8.0. However, the organic ligand was more effective in preventing or perturbing the growth of the crystals of boehmite when coprecipitated with Al than when added to soluble Al(OH)x species or preformed Al precipitates. Boehmite aged at temperatures ⩽50°C typically showed a fibrous morphology. Crystals with a rhombic habit were observed in some treatments after ageing at 140°C. Significant amounts (15–30% C) of tannate were present in the precipitates after prolonged ageing. This tannate was only partly (

The morphological properties, the mineralogy, and the chemical composition of Mn-Fe nodules, collected from an Alfisol in Southern China (Wuhan), were studied by optical microscopy (OM), transmission electron microscopy (TEM), and scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), total and sequential dissolution chemical analyses and differential x-ray diffraction (DXRD). This information is needed to gain a further understanding of nodule formation in soil environments and the influence of Mn and Fe oxides on the phyto-availability of both nutrients and toxic trace metals. Element quantification and mapping showed that Si, Al, Fe, Mn, Ca, K, and Ti were the main elements present in the nodules. Nodules were found to be highly variable in composition and in degree of banding of Fe and Mn. In spherical nodules, Fe and Mn were distributed mainly in concentric bands. With few exceptions, heavy metals were concentrated in the finest fraction (

Background —Oxidative stress is involved in the onset of several degenerative disorders, and epidemiological studies indicate that a high intake of dietary antioxidants, as in the case of the Mediterranean basin, is protective. Olive mill waste waters (OMWWs) are a byproduct of olive oil production rich in phenolic antioxidants, such as hydroxytyrosol. We tested the effects of a low dose of an OMWW extract in a model of sidestream smoke–induced oxidative stress in rats by evaluating the urinary excretion of 8-iso-prostaglandin (PG) F 2α (iPF 2α -III). Methods and Results —An OMWW extract (5 mg/kg, providing 414 μg/kg of hydroxytyrosol) was administered to rats daily for 4 days, during which time the animals were exposed to sidestream smoke for 20 minutes once a day. Daily urines were collected, and the urinary excretion of 8-iso-PGF 2α was evaluated as an index of oxidative stress–induced in vivo lipid peroxidation. The exposure of rats to passive smoking increased the urinary excretion of 8-iso-PGF 2α by 44±4.2% at 48 hours and by 55±10% at 96 hours. Treatment with the OMWW extract was able to completely prevent the increase at 48 hours and resulted in lower increments (34±18% versus 55±10%) of 8-iso-PGF 2α excretion at 96 hours. Conclusions —A low dose of hydroxytyrosol, administered through OMWW, reduces the consequences of sidestream smoke–induced oxidative stress in rats.

We studied the formation of OH–Al–humate–montmorillonite complexes as affected by the nature of the humic acid and the sequence of addition of montmorillonite, humic acid and hydrolytic species of Al. Complexes were prepared at pH 7.0 by different addition sequences of montmorillonite, 3 or 6 mmol Al and 5, 10 or 20 mg of humic acid per g of clay. d-spacings of samples ranged from 14.50 to 19.00 A vs. 11.70 A of montmorillonite. Interlayering of humic acids was promoted when preformed OH–Al–humate complexes were added to montmorillonite and partially impeded when the complexes were synthesized by neutralizing Al ions in the presence of montmorillonite. Humic acids were not interlayered in the absence of OH–Al-species, indicating that the hydrolytic products of Al play a vital role in the formation of organo–mineral complexes in natural environment.

It is well established that the adsorption of proteins on clay minerals is influenced by many factors.

Free radicals attack lipid molecules and initiate a chain of reactions that may trigger several diseases such as atherosclerosis and cancer. Several markers of oxidative stress have been proposed, including measurements of lipid peroxides and short-chain aldehydes levels and evaluation of conjugated diene formation. Although it is generally assumed that fatty acid oxidizability is directly proportional to their degree of unsaturation, little is known about the contribution of individual fatty acids to each of these markers. We investigated such contributions in a model of AAPH-mediated peroxidation of individual fatty acid micelles by assessing several indices of oxidative stress. The results suggest that the generation of oxidation products by individual fatty acids is not directly related to their degree of unsaturation and indicate that the differential contribution of individual fatty acids should be taken into account and more than one marker of lipid peroxidation should be included inin vivostudies of oxidative stress.

Phosphate adsorption and desorption by iron hydr(oxides) are geochemically important processes affecting water quality and soil fertility. Relatively little is known, however, about the interaction between phosphate and hematite, which after goethite is the most abundant iron hydr(oxide) in nature. To study the effect of morphology and other crystal properties of hematite on phosphorous adsorption and desorption, thirty hematites synthesized by different methods and differing widely in properties were used. Phosphate adsorption curves 1 and 124 days after P addition were adequately described by the Freundlich equation. The P adsorbed at an equilibrium concentration of 1 mg P/L (32 μM) at 1 and 124 days ( A 1 , A 124 ) ranged between 0.31 and 2.07 ( X = 1.03; SD = 0.53) μmol/m 2 , and between 0.54 and 2.72 ( X = 1.59; SD = 0.65) μmol/m 2 , respectively. The values of A decreased when the crystals and the X-ray coherently scattering domains became more platy in the c with respect to the a direction, supporting the hypothesis that the P-adsorbing faces are the nonbasal ones. Exponent b of the Freundlich equation, which gives a measure of the relative affinity of the adsorption sites, increased when domains and crystals became more platy, i.e., the more platy the crystal, the lower the proportion of high-affinity sites. The ratio between slow (1–124 days) and total (124 days) adsorption increased with decreasing affinity (higher b values) and was not related to microporosity. In comparison to goethite, the present results show that hematite has more variability in P-adsorption capacity, adsorbs on average less P per unit surface area, has less affinity for phosphate, and exhibits a more important slow adsorption component. The proportion of the adsorbed phosphate that could be desorbed by an anion-exchange resin or by electroultrafiltration was affected by those hematite properties affecting diffusion (e.g., microporosity). Isotopically exchangeable P did not depend on morphological or crystalline properties. Irrespective of the method, desorbability, i.e., the proportion of adsorbed phosphate that was desorbable or isotopically exchangeable, was positively correlated to parameter b , suggesting that more desorption occurs in samples having a higher proportion of low-affinity sites. Desorbability was also positively correlated to the ratio between slow and total adsorption. It appears, therefore, that slow adsorption and desorption take place preferentially at low-affinity sites.

The human monocytic leukemia cell line THP-1 is depleted of the long-chain n − 6, AA, when compared to human monocytes. This reflects the low availability of this FA in the growth medium generally used for cultured cells. The effects of AA, as well as EPA, supplementation of THP-1 cells on the incorporation of these FA in cell PL, especially in PC and PE, was investigated. In addition the incorporation of labeled AA in PL from THP-1 cells was compared to that in human monocytes. Measurements were done through HPLC separation of PL, detected by UV absorption and radioactivity, FA analysis by GC and characterization of PC subclasses by FAB-MS. Marked differences were observed in the incorporation of the two FA in cell PL, particularly two PC subclasses, and in the accumulation in individual PL after supplementation of THP-1 cells. Accumulation of AA and EPA in THP-1 cells appeared to be mutually independent. The incorporation of AA was also quite differeat in THP-1 from that in monocytes. Thus, characterization of the FA content in lipids of cultured cells is an essential requirement for optimal utilization of these cells.

The administration to male rats of 5 en % fish oil (FO) as supplement to a diet containing 5 en % corn oil (CO), selectively and markedly decreased arterial parameters (6-keto-PGF1 alpha formation and platelet antiaggregatory activity) assessed in isolated aortic segments perfused with autologous platelet rich plasma (PRP). Platelet parameters (ADP-induced aggregation, TxB2 formation in thrombin-stimulated PRP and sensitivity to exogenous PGI2) were instead minimally affected. Eicosapentaenoic acid (EPA, 20:5 n-3) did not accumulate in plasma, platelet and aorta lipids and arachidonic acid (AA, 20:4 n-6) levels declined markedly only in the plasma compartment. When FO was given alone at the same 5 en % level, both arterial and platelet parameters were similarly affected. EPA accumulated in plasma cholesterol esters and was present in appreciable concentrations also in platelets and aortic walls. AA levels declined markedly in plasma lipids and appreciably also in platelet and aorta lipids. It is concluded that a) arterial and platelet parameters are differentially affected by FO administration depending upon the presence of n-6 polyunsaturated fatty acids in the diet, b) 6-keto-PGF1 alpha production by arterial tissue does not seem to be related to changes of PG precursor fatty acid levels in the phospholipid fraction.

Summary The coumarin derivative AD6 was administered i.v. at the dose of 3 mg/kg/day to hypercholesterolaemic rabbits for a period of three weeks, while continuing the hypercholesterolaemic treatment (HC + AD6). A second group of hypercholesterolaemic (HC) rabbits was injected with saline and a third group of animals was composed of normal rabbits (N). Platelet aggregatory responses to arachidonic acid (AA) and collagen, thromboxane B2 (TxB2) formation after stimulation with collagen, 6 keto PGF1α formation following perfusion of isolated aortas with platelet-rich plasmas (PRP) and sensitivity of PRP to the inhibitory activity of exogenous prostacyclin (PGI2) were studied. Platelets of the HC rabbits were hyperactive to AA, were less sensitive to PGI2, produced less TxB2 after collagen stimulation, and perfused aortas of the same HC group produced more 6 keto PGF1α in respect to the N animals. Administration of AD6 to the HC animals normalized TxB2 production in stimulated PRP, platelet sensitivity to PGI2 and 6 keto PGF1α production in perfused aortas.