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Comparison between several reactors with Trametes versicolor immobilized on lignocellulosic support for the continuous treatments of hospital wastewater

J.Torána. P.Blánqueza and G.Caminal

Bioresource Technology 243, 966-974, 2017

Hospital wastewater is a major source of pharmaceutically active compounds (PhACs), which are not all removed in conventional wastewater treatment plants. White rot fungi can degrade PhACs, but their application has been limited to non-sterile conditions due to the competition with other microorganisms for growth. In this study, immobilization of Trametes versicolor on different lignocellulosic supports was studied as strategy to ensure fungal survival under continuous treatment conditions. A fluidized bed reactor and a trickling packed-bed reactor with T. versicolor immobilized on pallet wood were employed for the removal of ibuprofen, ketoprofen and naproxen. Best results were obtained with the trickling packed-bed reactor, which operated for 49 days with high removal values in real hospital wastewater.
 

Structural study of a new HIV-1 entry inhibitor and interaction with the HIV-1 fusion peptide in dodecylphosphocholine micelles

Yolanda Pérez, María José Gómara, Eloísa Yuste, Patricia Gómez-Gutierrez, Juan Jesús Pérez, and Isabel Haro

Chem. Eur. J. 10.1002/chem.201702531

Previous studies support the hypothesis that the envelope GB virus C E1 protein interferes HIV-1 entry and a peptide, derived from the region (139-156) of this protein, has defined as a novel HIV-1 entry inhibitor. In this work, we firstly focus on the characterization of the peptide structural features which are determinant for its anti-HIV-1 activity and secondly, on the study of its interaction of with the proposed viral target (the HIV-1 fusion peptide). We report the peptide structure determined by NMR spectroscopy in DPC micelles solved using restrained molecular dynamics calculations. The acquisition of different NMR experiments in DPC micelles (peptide-peptide titration, diffusion NMR and addition of paramagnetic relaxation agents) allows the proposal of an inhibition mechanism. We conclude that an 18-mer peptide from nonpathogenic E1 GBV-C protein, with a helix-turn-helix structure, inhibits HIV-1 by binding to the HIV-1 fusion peptide at membrane level interfering with those domains in HIV-1 that are critical for stabilizing the six-helix bundle formation in a membranous environment.

 

Twisted intramolecular charge transfer in a carbazole-based chromophore. The stable [(4-N-carbazolyl)-2,3,5,6-tetrachlorophenyl]bis(2,3,5,6-tetrachlorophenyl)methyl radical

Luis Juliá,  Alejandra Gilabert,  Lluís Fajarí,  Ignasi Sirés,  Marta Reig,  Enric Brillas,  Dolores Velasco Castrillo  and  Josep M. Anglada

New J. Chem., 2017

A neutral stable organic radical adduct 1 composed of a donor-acceptor dyad is reported. The electron-donor part is the carbazolyl ring directly linked to the electron-acceptor polychlorotriphenylmethyl radical through the para-position of a phenyl ring. In the synthetic procedure a C(sp2)-H bond is transformed into a C(sp2)-N bond through the radical-radical cross-coupling process. Theoretical calculations predict that the tetrachlorophenyl bridge moiety lies perpendicular to the carbazolyl group to minimize the repulsion with the chlorine atoms in ortho. The electron paramagnetic resonance (epr) spectrum of 1 exhibits a small coupling of the electronic spin with the carbazolyl nitrogen (0.32 G), the spin density being mainly located in the central sp2 carbon atom (30.22 G). The radical adduct presents a charge transfer band (? = 598-640 nm) showing hypsochromic shift with solvent polarity. In DMF solution, 1 exhibits a new weak band (? = 493 nm) which is tentatively attributed to a zwitterionic structure of the molecule resulting from a net electron transfer from the nitrogen to the central sp2 carbon atom. Cyclic voltammetry of 1 confirms the amphoteric character of the molecule. Computed values of ionization potential (IP) and electron affinity (EA) are in good agreement with the experimental values.
 

Pharmaceutical versatility of cationic niosomes derived from amino acid-based surfactants: Skin penetration behavior and controlled drug release

Muzzalupo R., Pérez L., Pinazo A., Tavano L.

International Journal of Pharmaceutics 529, 1-2, 245-252, 2017

The natural capability shown by cationic vesicles in interacting with negatively charged surfaces or biomolecules has recently attracted increased interest. Important pharmacological advantages include the selective targeting of the tumour vasculature, the promotion of permeation across cell membranes, as well as the influence of cationic vesicles on drug delivery. Accordingly, cationic amphiphiles derived from amino acids may represent an alternative to traditional synthetic cationic surfactants due to their lower cytotoxicity. The importance of a synthesized lysine-based gemini surfactant (labelled C6(LL)2) was evaluated in drug delivery by designing cationic niosomes as usable pharmaceutical tools of chemotherapeutics and antibiotics, respectively like methotrexate and tetracycline. The influence of formulation factors on the vesicles’ physical-chemical properties, drug entrapment efficiency, in vitro release and ex-vivo skin permeation were investigated. A niosomal gel containing the gemini surfactant was also tested as a viable multi-component topical formulation. Results indicate that in the presence of cholesterol, C6(LL)2 was able to form stable and nanosized niosomes, loading hydrophilic or hydrophobic molecules. Furthermore, in vitro release studies and ex-vivo permeation profiles showed that C6(LL)2-based vesicles behave as sustained and controlled delivery systems in the case of parenteral administration, and as drug percutaneous permeation enhancers after topical application. Finally, cationic C6(LL)2 acts as a carrier constituent, conferring peculiar and interesting functionality to the final formulation.
 

Influence of crosslinked alginate on drug release from highly concentrated emulsions

Pablo Bonilla, Eva M.Arias, Conxita Solans and María José García-Celma

Colloids and Surfaces A: Physicochemical and Engineering Aspects 2017

Biocompatible water-in-oil (W/O) and oil-in-water (W/O) highly concentrated emulsions (HIPREs) have been formed at 25 °C, in systems consisting of aqueous component/castor oil derivative surfactant/oil compound. In both kinds of emulsions the concentration of internal phase was 83% and the aqueous component consisted of water, 1% sodium alginate solution or a mixture of sodium alginate solution and calcium chloride solution (crosslinked calcium alginate). Ketoprofen (KP) or clindamycine hydrochloride (CH) were solubilized in both kinds of HIPREs and the influence of the composition of the aqueous phase on drug release was studied. Droplet sizes of the W/O HIPREs formed were in the nanometric range, being smaller than other HIPREs described in the literature. Dynamic viscoelastic measurements showed an increase in the elastic modulus (G’) of the emulsions in the presence of alginate or crosslinked alginate. The influence of the order of incorporation of alginate and calcium chloride on the viscosity was demonstrated, as an indication of crosslinking efficiency. KP release to a PBS receptor solution was slower when crosslinked alginate was formed in the internal phase of W/O HIPREs. In contrast, the influence of crosslinked alginate on the release of CH was negligible and the solubility of the drug in the disperse phase demonstrated to be the main mechanism responsible of CH diffusion. The results obtained suggest that the formation of a crosslinked alginate matrix in the internal phase of HIPREs is a factor that has to be taken into account in the development of controlled drug delivery systems.
 

Green Catanionic Gemini Surfactant–Lichenysin Mixture: Improved Surface, Antimicrobial, and Physiological Properties

Albert Ruiz, Aurora Pinazo, Lourdes Pérez , Angeles Manresa, and Ana M. Marqués

ACS Appl. Mater. Interfaces, 2017, 9 (27), pp 22121–22131

Catanionic surfactant mixtures form a wide variety of organized assemblies and aggregates with improved physicochemical and biological properties. The green catanionic mixture NaN?-Bis(Nacaproylarginine) a,?-propyldiamide (C3(CA)2):Lichenysin (molar ratio 8:2) showed antimicrobial synergies against Yersinia enterocolitica, Bacillus subtilis, Escherichia coli O157:H7, and Candida albicans. Flow cytometry and viability studies indicated that this catanionic mixture increases the probability of Y. enterocolitica (38.2%) and B. subtilis (17.1%) cells entering a viable but nonculturable state. Zeta potential showed that one of the cationic charges of C3(CA)2 is neutralized by Lichenysin. An isotherm study demonstrated the formation of a stable aggregate between the two surfactants. The catanionic aggregate was able to interact with bacterial phospholipids. The lowest hemolysis (22.1 µM) was obtained with the catanionic mixture, although an irritant potential (0.70) was characterized. According to the therapeutic index, the C3(CA)2:Lichenysin mixture was the formulation least toxic to eukaryotic cells. Partial neutralization of C3(CA)2 by Lichenysin modified the mode of action that enhances the transition of bacterial cells into a viable but nonculturable state (VBNC) and improved the cell selectivity.
 

Study of the interaction of GB virus C/Hepatitis G virus fusion peptides belonging to the E2 protein with phospholipid Langmuir monolayers

Silvia Pérez-López. Marta Espina. M José Gómara. José Luis Fidalgo. M. Asunción Alsina. Concepció Mestres. José Miñones Conde

Colloids and Surfaces B: Biointerfaces 158, 278-286, 2017


In order to determine the ability of 1,2-dipalmitoyl phosphatidylcholine (DPPC) and 1,2-dioleoyl phosphatidylglycerol (DOPG) to host peptide sequences belonging to the E2 protein of GBV virus C/Hepatitis G virus, the behaviour of Langmuir monolayers formed by these phospholipids and E2 (12–26), E2 (354–363) and E2 (chimeric) peptide sequences was analysed from data of surface pressure (p) versus area per molecule (A) isotherms, compression modulus (Cs-1), excess Gibbs energy of mixing (?Gexc) and total Gibbs energy of mixing (?Gmix). Three different behaviours were observed. Mixed films of E2 (12–26) with DPPC or DOPC showed negative values for the excess thermodynamic functions, and thus attractive interactions between mixed films components are greater than in ideal films. Mixtures of E2 (354–363) with DPPC or DOPG, exhibited positive values of excess functions, evidencing weaker interactions in the mixed films in relation to those of pure components. Finally, positive and negative excess functions were observed in E2 (chimeric)/DPPC or DOPG mixed films, depending on their composition. In short, the interaction between the phospholipids used in this work as models of cell membranes and E2 peptides varies with the type of phospholipid and the nature of the peptide (size, bulky, hydrophobicity and electric charge).

 

An experimental and theoretical comparative study of the entrapment and release of dexamethasone from micellar and vesicular aggregates of PAMAM-PCL dendrimers

Avila-Salas, F.; Pereira, A.; Rojas, M. A.; Saavedra-Torres, M.; Montecinos, R.; Bonardd, S.; Quezada, C.; Saldías, S.; Díaz, D. D.; Leiva, A.; Rodic, D.; Saldías, C.

Eur. Polym. J. 93, 507-520, 2017
Self-assembling dendrimers in aqueous solution have attracted many efforts focused on the rationalization and development of consistent strategies to design carriers that are useful in the field of drug release. In this way, amphiphilic dendrimers with specific structural features and self-assembling behaviors in aqueous media would enable drug entrapment as well as drug release over a determined time period. In this work, we report the synthesis and characterization of poly(amido-amine)-b-poly(ε-caprolactone) (PAMAM-PCL) amphiphilic dendrimers and their use in the preparation of micellar and vesicular aggregates. The ability to form suitable carriers of amphiphilic dendrimers using dexamethasone as a model drug was assessed. Using the ultrasonic-assisted precipitation method, PAMAM-PCL 1 and PAMAM-PCL 2 self-assembled into micelles and vesicles were obtained. The critical aggregation concentration (C.A.C.), hydrophilic-hydrophobic balance and aggregate sizes were found to mainly depend on the type of dendrimer used. Characterization of PAMAM-PCL aggregates by transmission electron microscopy (TEM), dynamic light scattering (DLS), UV–visible, fluorescence and zeta potential (ξ) was carried out. The standard free energies of solubilization, ΔGs°, of dexamethasone into PAMAM-PCL aggregates were obtained from the partition coefficient between the aqueous and the aggregate phases. ΔGs° is notoriously dependent on the type of dendrimer and aggregate employed. In addition, by in vitro studies, a combination of diffusion and eroding dendrimeric matrix mechanisms for drug release could be established. Finally, all-atom molecular dynamic simulations helped us to gain insight into the conformational behavior and interactions between the PAMAM-PCL dendrimer and dexamethasone in different solvents and their respective mixtures with water.
 

Fungal treatment for the removal of endocrine disrupting compounds from reverse osmosis concentrate: Identification and monitoring of transformation products of benzotriazoles

Marta Llorca, Marina Badia-Fabregat, Sara Rodríguez-Mozaz, Glòria Caminal, Teresa Vicent, Damià Barceló

Chemosphere, 184, 1054–1070, 2017

The removal of 27 endocrine-disrupting compounds and related compounds (suspect effect) from a reverse osmosis concentrate using an alternative decontamination method based on a fungal treatment involving Trametes versicolor was assessed. In addition to chemical analysis, the toxicity of the treated water during the treatment was monitored using a bioluminescence inhibition test and estrogenic and anti-estrogenic tests.
The compounds 1H-benzotriazole (BTZ) and two tolyltriazoles (TTZs), 4-methyl-1H-benzotriazole (4-MBTZ) and 5-methyl-1H-benzotriazole (5-MBTZ), were present in the reverse osmosis concentrate at the highest concentrations (7.4 and 12.8 μg L−1, respectively) and were partially removed by the fungal treatment under sterile conditions (58% for BTZ and 92% for TTZs) and non-sterile conditions, although to lesser extents (32% for BTZ and 50% for TTZs).
Individual biotransformation studies of BTZ and the TTZs by T. versicolor in a synthetic medium and further analysis via on-line turbulent flow chromatography coupled to an HRMS-Orbitrap allowed the tentative identification of the transformation products (TPs). Six TPs were postulated for BTZ, two TPs were postulated for 4-MBTZ, and four TPs were postulated for 5-MBTZ. Most of these TPs are suggested to have been generated by conjugation with some sugars and via the methylation of the triazole group. Only TP 148 A, postulated to be derived from the biotransformation of BTZ, was observed in the effluent of the bioreactor treating the reverse osmosis concentrate.
 

Flight and swarming behaviour of Culicoides species (Diptera: Ceratopogonidae) on a livestock farm in Northern Spain

Mikel A. González, Pedro M. Alarcón-Elbal, Gert J. Venter & Sergio López

Veterinaria Italiana 53, 2, 157-166, 2017

The efficacy of sweep nets and a CDC white light-suction trap for the sampling of Culicoides species (Diptera: Ceratopogonidae) were compared on a livestock farm in Northern Spain during the Summer of 2013. A total of 6,082 specimens representing 26 species were collected with sweep nets in 4 areas at different heights (ground level, 1.5 m, and 3 m), and 8,463 specimens representing 28 species with a single white light trap. Eight species - Culicoides brunnicans, Culicoides punctatus, Culicoides obsoletus/Culicoides scoticus, Culicoides lupicaris, Culcoides picturatus, Culicoides achrayi, and Culicoides simulator - were dominant and accounted for 97.4% and 97.2% of the total specimens collected with both methods, sweep nets, and light traps, respectively. The sex ratios with sweep netting and light trapping were strongly female biased (78.4% and 97.1%, respectively). Nulliparous and parous females were predominantly captured with both methods. A high percentage (17%) of gravid females was, however, captured on manure at ground level while sweeping. Searches for male swarms revealed the presence of several C. punctatus swarms consisting of 26 to 196 males and 3 swarms of C. obsoletus that ranged from 1 to 12 males in size. This study suggested that both methods are suitable and complementary tools for Culicoides sampling.
 


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