Immobilization of drugs for glaucoma treatment

Recently there have been some developments in the preparation of controlled drug delivery systems for glaucoma. Many materials are being used in this area, namely gelatine and chitosan. Both of them present high levels of biocompatibility and biodegradability. In this paper, we wish to report the work we have been doing on the preparation and characterization of hydrogels based on gelatine and chitosan. The crosslinking agents used were 1-(3-(Dimethylamino)propyl)-3-Ethylcarbodiimide hydrocholide (CDI), 1,4-Butanodiol diglycidyl ether (epoxyde 1), Ethylene glycol diglycidyl ether (epoxyde 2) and genipin. The results obtained showed that all of the films were hydrogels. The surface and transversal cut showed a porous surface in all the films. The thermal analysis proved the modifications in the polymeric chains, with the stabilization of all of them by the crosslinking agents. The release pattern indicates that the gelatine films were the best since they release the adequate proportion of drug. Finally, the cytotoxicity showed that the gelatine films were all biocompatible, specially the ones crosslinked with one of the Epoxydes.     

Direct low-temperature synthesis of rutile nanostructures in ionic liquids

The direct synthesis of crystalline titania nanorods by sol-gel chemistry in a special ionic liquid is reported. Unexpectedly, the high-temperature modification, rutile, is obtained directly under ambient conditions. X-ray diffraction and high-resolution transmission electron microscopy measurements support the highly crystalline and structural quality of the sample. The phase-directing property of the ionic liquids is attributable to the imide group in the counter ion, which exhibits strong interaction with specific rutile faces. Lithium insertion experiments were performed and revealed high and reversible loading capacities of up to 200 mAh g(-1).     

An efficient any language approach for the integration of phrases in document retrieval

In this paper, we address the problem of the exploitation of text phrases in a multilingual context. We propose a technique to benefit from multi-word units in adhoc document retrieval, whatever the language of the document collection. We present principles to optimize the performance improvement obtained through this approach. The work is validated through retrieval experiments conducted on Chinese, Japanese, Korean and English.     

Sugar Surfactant-Based Shampoos

Naturally derived surfactants in hair care products are a trend in cosmetic technology. This study aimed to formulate and fully characterize the performance of shampoos with sugar-derived surfactants, namely, the alkyl polyglucosides decyl glucoside and coco-glucoside. In addition, different thickeners and conditioning ingredients were added to improve the formulation properties. A sodium laureth sulfate (SLES) formulation was used as control. Rheology, pH, foaming, contact angles on a keratin surface, and surface tensions were determined. The safety of the formulations was evaluated by in vitro cytotoxicity studies using the human keratinocyte HaCaT cell line and human retinal pigment epithelial cells ARPE-19. The efficacies were studied by in vitro hair combing force assays and in vivo sensorial analysis. The formulated sugar surfactant-based shampoos showed the following properties: (i) pH values higher than those of SLES (which were posteriorly lowered with lactic acid); (ii) higher foamability than SLES, and high wettability; (iii) Newtonian behavior and predominance of liquid state with a suitable viscosity; (iv) low cytotoxicity in both human keratinocytes and retinal cell lines (in contrast to SLES); (v) easier hair combing than SLES, when Polyquaternium-7 was used as conditioner; (vi) efficient and gentle hair washing; and (vii) favorable sensorial analysis confirming the previous washing properties. In conclusion, the sugar surfactants had a considerable impact in the properties of the shampoo formulations, in terms of both hair cleansing properties and efficacy, as demonstrated here. These favorable outcomes clearly support the use of these ingredients in shampoo formulation design.     

Hologram QSAR Models of a Series of 6-Arylquinazolin-4-Amine Inhibitors of a New Alzheimer’s Disease Target: Dual Specificity Tyrosine-Phosphorylation-Regulated Kinase-1A Enzyme

Dual specificity tyrosine-phosphorylation-regulated kinase-1A (DYRK1A) is an enzyme directly involved in Alzheimer’s disease, since its increased expression leads to β-amyloidosis, Tau protein aggregation, and subsequent formation of neurofibrillary tangles. Hologram quantitative structure-activity relationship (HQSAR, 2D fragment-based) models were developed for a series of 6-arylquinazolin-4-amine inhibitors (36 training, 10 test) of DYRK1A. The best HQSAR model (q² = 0.757; SE_cv = 0.493; R² = 0.937; SE = 0.251; R²pred = 0.659) presents high goodness-of-fit (R² > 0.9), as well as high internal (q² > 0.7) and external (R²pred > 0.5) predictive power. The fragments that increase and decrease the biological activity values were addressed using the colored atomic contribution maps provided by the method. The HQSAR contribution map of the best model is an important tool to understand the activity profiles of new derivatives and may provide information for further design of novel DYRK1A inhibitors.     

Total Phenolics of Virgin Olive Oils Highly Correlate with the Hydrogen Atom Transfer Mechanism of Antioxidant Capacity

Polar extracts of extra‐virgin olive oils (EVOO) contain a large number of phenolic compounds with antioxidant properties. The antioxidant capacity can be measured by different reaction mechanisms, as the single electron transfer (SET) or the hydrogen atom transfer (HAT). In this work, the total phenolic content (TPC) by the Folin‐Ciocalteu method and its correlation with four antioxidant capacity assays (FRAP, ABTS, DPPH^? and ORAC) were evaluated for EVOO polar extracts. It was observed that the higher the total phenolic compounds in the EVOO extracts, the higher the antioxidant capacities, regardless of the method employed. The reaction mechanism observed for TPC by Folin‐Ciocalteu method and also for FRAP, ABTS and DPPH^? antioxidant capacity assays is a single electron transfer, thus, a high correlation among their results is expected. However, the correlation between TPC and ORAC results was also high and significant, allowing to conclude that EVOO phenolic compounds are able to react by the hydrogen atom transfer mechanism, which indicates that they can act as effective radical chain‐breaking antioxidants. These results suggest that, for the EVOO polar extracts, TPC by Folin‐Ciocalteu and ORAC assays could be sufficient to evaluate their in vitro antioxidant capacity.     

Bisamidate Prodrugs of 2‐Substituted 9‐[2‐(Phosphonomethoxy)ethyl]adenine (PMEA,adefovir) as Selective Inhibitors of Adenylate Cyclase Toxin from Bordetella pertussis

Novel small‐molecule agents to treat Bordetella pertussis infections are highly desirable, as pertussis (whooping cough) remains a serious health threat worldwide. In this study, a series of 2‐substituted derivatives of 9‐[2‐(phosphonomethoxy)ethyl]adenine (PMEA, adefovir), in their isopropyl ester bis(L ‐phenylalanine) prodrug form, were designed and synthesized as potent inhibitors of adenylate cyclase toxin (ACT) isolated from B. pertussis. The series consists of PMEA analogues bearing either a linear or branched aliphatic chain or a heteroatom at the C2 position of the purine moiety. Compounds with a small C2 substituent showed high potency against ACT without cytotoxic effects as well as good selectivity over human adenylate cyclase isoforms AC1, AC2, and AC5. The most potent ACT inhibitor was found to be the bisamidate prodrug of the 2‐fluoro PMEA derivative (IC₅₀=0.145 μM ). Although the bisamidate prodrugs reported herein exhibit overall lower activity than the bis(pivaloyloxymethyl) prodrug (adefovir dipivoxil), their toxicity and plasma stability profiles are superior. Furthermore, the bisamidate prodrug was shown to be more stable in plasma than in macrophage homogenate, indicating that the free phosphonate can be effectively distributed to target tissues, such as the lungs. Thus, ACT inhibitors based on acyclic nucleoside phosphonates may represent a new strategy to treat whooping cough.     

Co‐administration of Antimicrobial Peptides Enhances Toll‐like Receptor 4 Antagonist Activity of a Synthetic Glycolipid

This study examines the effect of co‐administration of antimicrobial peptides and the synthetic glycolipid FP7, which is active in inhibiting inflammatory cytokine production caused by TLR4 activation and signaling. The co‐administration of two lipopolysaccharide (LPS)‐neutralizing peptides (a cecropin A–melittin hybrid peptide and a human cathelicidin) enhances by an order of magnitude the potency of FP7 in blocking the TLR4 signal. Interestingly, this is not an additional effect of LPS neutralization by peptides, because it also occurs if cells are stimulated by the plant lectin phytohemagglutinin, a non‐LPS TLR4 agonist. Our data suggest a dual mechanism of action for the peptides, not exclusively based on LPS binding and neutralization, but also on a direct effect on the LPS‐binding proteins of the TLR4 receptor complex. NMR experiments in solution show that peptide addition changes the aggregation state of FP7, promoting the formation of larger micelles. These results suggest a relationship between the aggregation state of lipid A‐like ligands and the type and intensity of the TLR4 response.