Design of a Nasal Spray Based on Cardiospermum halicacabum Extract Loaded in Phospholipid Vesicles Enriched with Gelatin or Chondroitin Sulfate

The extract of Cardiospermum halicacabum L. (C. halicacabum) obtained from flower, leaf and vine was loaded into modified phospholipid vesicles aiming at obtaining sprayable, biocompatible and effective nasal spray formulations for the treatment of nasopharyngeal diseases. Penetration enhancer-containing vesicles (PEVs) and hyalurosomes were formulated, and stabilized by adding a commercial gelatin from fish (20 mg/mL) or chondroitin sulfate from catshark cartilages (Scyliorhinus canicula, 20 mg/mL). Cryo-TEM images confirmed the formation of spherical vesicles, while photon correlation spectroscopy analysis disclosed the formation of small and negatively-charged vesicles. PEVs were the smaller vesicles (~100 nm) along with gelatin-hyalurosomes (~120 nm), while chondroitin-PEVs and chondroitin-hyalurosomes were larger (~160 nm). Dispersions prepared with chondroitin sulfate were more homogeneous, as the polydispersity index was ~0.15. The in vitro analysis of the droplet size distribution, average velocity module and spray cone angle suggested a good spray-ability and deposition of formulations in the nasal cavity, as the mean diameter of the droplets was in the range recommended by the Food and Drug Administration for nasal targets. The spray plume analysis confirmed the ability of PEVs, gelatin-PEVs, hyalurosomes and gelatin-hyalurosomes to be atomized in fine droplets homogenously distributed in a full cone plume, with an angle ranging from 25 to 30°. Moreover, vesicles were highly biocompatible and capable of protecting the epithelial cells against oxidative damage, thus preventing the inflammatory state.     

Spectroscopic investigation of interactions between dipeptides and vanadate(V) in solution

The reaction of vanadate(V) with a series of dipeptides (Val-Gln, Ala-Gln, Gly-Gln, Gly-Glu, and Ala-Gly) was investigated by UV-visible spectroscopy and multinuclear ((51)V, (14)N, (13)C) NMR spectroscopy in solution. It was possible to evaluate the formation constants of the corresponding complexes for which a molecular structure was proposed. Complex formation is favored by the presence of a functionalized or a sterically demanding side chain. The Val-Gln dipeptide which combines both properties exhibits one of the highest formation constant reported so far for dipeptides.     

Peroxyoxalate High‐Energy Intermediate is Efficiently Decomposed by the Catalyst Imidazole

The peroxyoxalate reaction is a highly efficient chemiluminescence system, its chemiexcitation process involving the intermolecular interaction between an activator (ACT) and the high‐energy intermediate (HEI) of the reaction. Typically, the HEI is generated through the reaction of an oxalate ester with H₂O₂, in the presence of a basic/nucleophilic catalyst, such as imidazole (IMI‐H). IMI‐H, besides catalyzing the formation of the HEI, is also known to decompose this peroxidic intermediate. Despite that, up to now, no rate constant value has been determined for such significant interaction. Through kinetic measurements, we have observed that IMI‐H is roughly four times more efficient than 9,10‐diphenylanthracene (DPA), a classic ACT, in catalyzing the decomposition of the HEI by a bimolecular electron transfer reaction through a Chemically Initiated Electron Exchange Luminescence‐like process. For instance, when IMI‐H and DPA are at the same concentration, 78% of the generated HEI is actually consumed by the nonemissive bimolecular interaction with IMI‐H. We have obtained an average singlet excited state formation quantum yield, at infinite ACT concentration, of (5.5 ± 0.5) × 10^?2 E mol^?1, determined at five different IMI‐H concentrations. This ultimately suggests that the yield of formation of HEI actually does not depend on the IMI‐H concentration.     

Binding of VIVO2+, VIVOL,VIVOL2 and VVO2L Moieties to Proteins: X-ray/Theoretical Characterization and Biological Implications

Vanadium compounds have frequently been proposed as therapeutics, but their application has been hampered by the lack of information on the different V-containing species that may form and how these interact with blood and cell proteins, and with enzymes. Herein, we report several resolved crystal structures of lysozyme with bound V^IVO²⁺ and V^IVOL²⁺, where L=2,2’-bipyridine or 1,10-phenanthroline (phen), and of trypsin with V^IVO(picolinato)₂ and V^VO₂(phen)⁺ moieties. Computational studies complete the refinement and shed light on the relevant role of hydrophobic interactions, hydrogen bonds, and microsolvation in stabilizating the structure. Noteworthy is that the trypsin−V^VO₂(phen) and trypsin−V^IVO(OH)(phen) adducts correspond to similar energies, thus suggesting a possible interconversion under physiological/biological conditions. The obtained data support the relevance of hydrolysis of V^IV and V^V complexes in the several types of binding established with proteins and the formation of different adducts that might contribute to their pharmacological action, and significantly widen our knowledge of vanadium–protein interactions.     

New Tris(hydroxypyridinones) as Iron and Aluminium Sequestering Agents: Synthesis,Complexation and In Vivo Studies

Two new tripodal tris(3‐hydroxy‐4‐pyridinone) hexadentate chelators—NTA(BuHP)₃ and NTP(PrHP)₃ (NTA=nitrilotriacetic acid, NTP=nitrilotripropionic acid, HP=hydroxypyridone)—have been developed and studied in solution for their iron and aluminium binding affinity, and also assayed in vivo for their capacity to remove metal from an animal model that is overloaded. These chelators are positional isomers, possessing identical general structures based on aminotricarboxylic acid skeletons attached to three bidentate 3‐hydroxy‐4‐pyridinones (3,4‐HPs), but differing in the position of the amide linkage along the chelating “arm”. In spite of expected differences in the tripodal ligands, such as acidity and hydrogen‐bonding networks, they share important properties, namely, a mild hydrophilic character (log P ca. ?1.2 to ?1.4) and a strong chelating affinity for Fe and Al (pFe=27.9 and pAl=22.0 for NTA(BuHP)₃; pFe=29.4 and pAl=22.4 for NTP(PrHP)₃). They also evidenced identical effects on the biodistribution and on the excretion of a radiotracer (⁶⁷Ga) previously administered to mice, as models of iron overload animals. Comparison of the new compounds with reported analogues shows good improvement in terms of solution and in vivo sequestering properties, thus giving support to expectations about their potential clinical application as metal removal agents.     

Dispersive liquid-liquid microextraction of organophosphorous pesticides using nonhalogenated solvents

Dispersive liquid-liquid microextraction (DLLME) combined with gas chromatography and mass spectrometry (GC-MS) was applied to the determination of five organophosphorous pesticides (OPPs) in water samples. The analytes included in this study were prophos, diazinon, chlorpyrifos methyl, fenchlorphos, and chlorpyrifos. The use of nonhalogenated solvents (cyclohexane, heptane, and octane) as extraction solvents was investigated using acetone, acetonitrile, or methanol, as dispersion solvents. The combination of less polar dispersion solvents (1-propanol and 2-propanol) and nonhalogenated extraction solvents was also studied in dispersive liquid-liquid microextraction for the first time. Several experimental conditions were tested (nature and volume of extraction solvents, nature and volume of dispersion solvents, salting-out effect) and the corresponding enrichment factors and recoveries were evaluated. The best microextraction condition was obtained using 50 μL of cyclohexane and 0.3 mL of 1-propanol. The detection and quantification limits were in the low ppt range, with values between 3.3-8.0 ng/L and 11.0-26.6 ng/L, respectively. Relative standard deviations were between 6.6 and 13.1% for a fortification level of 500 ng/L. At the same fortification level, the relative recoveries (RR) of Alvito's dam water, Judeu's river water, and well water samples were in the range of 50.3-97.1%.     

The role of predator overlap in the robustness and extinction of a four species predator-prey network

Predators and preys often form species networks with asymmetric patterns of interaction. We study the dynamics of a four species network consisting of two weakly connected predator-prey pairs. We focus our analysis on the effects of the cross interaction between the predator of the first pair and the prey of the second pair. This is an example where the predator overlap, which is the proportion of predators that a given prey shares with other preys, is not uniform across the network due to asymmetries in patterns of interaction. We explore the behavior of the system under different interaction strengths and study the dynamics of survival and extinction. In particular, we consider situations in which the four species have initial populations lower than their long-term equilibrium, simulating catastrophic situations in which their abundances are reduced due to human action or environmental change. We show that, under these reduced initial conditions, and depending on the strength of the cross interaction, the populations tend to oscillate before re-equilibrating, disturbing the community equilibrium and sometimes reaching values that are only a small fraction of the equilibrium population, potentially leading to their extinction. We predict that, contrary to one’s intuition, the most likely scenario is the extinction of the less predated preys.     

Estimation in integer‐valued moving average models

The paper presents new characterizations of the integer‐valued moving average model. For four model variants, we give moments and probability generating functions. Yule–Walker and conditional least‐squares estimators are obtained and studied by Monte Carlo simulation. A new generalized method of moment estimator based on probability generating functions is presented and shown to be consistent and asymptotically normal. The small sample performance is in some instances better than those of alternative estimators. Copyright © 2001 John Wiley & Sons, Ltd.     

Enzymatic removal of cellulose from cotton/polyester fabric blends

The production of light-weight polyester fabrics from a polyester/cotton blended fabric, by means of the enzymatic removal of the cellulosic part of the material, was investigated. The removal of cotton from the blended fabric yielded more than 80% of insoluble microfibrillar material by the combined action of high beating effects and cellulase hydrolysis.Other major features of this enzymatic process for converting cotton fibers into microfibrillar material are bath ratio, enzyme dosage and treatment time.