Identification of Phenylpyrazolone Dimers as a New Class of Anti-Trypanosoma cruzi Agents

Chagas disease is becoming a worldwide problem; it is currently estimated that over six million people are infected. The two drugs in current use, benznidazole and nifurtimox, require long treatment regimens, show limited efficacy in the chronic phase of infection, and are known to cause adverse effects. Phenotypic screening of an in-house library led to the identification of 2,2′-methylenebis(5-(4-bromophenyl)-4,4-dimethyl-2,4-dihydro-3H-pyrazol-3-one), a phenyldihydropyrazolone dimer, which shows an in vitro pIC₅₀ value of 5.4 against Trypanosoma cruzi. Initial optimization was done by varying substituents of the phenyl ring, after which attempts were made to replace the phenyl ring. Finally, the linker between the dimer units was varied, ultimately leading to 2,2′-methylenebis(5-(3-bromo-4-methoxyphenyl)-4,4-dimethyl-2,4-dihydro-3H-pyrazol-3-one (NPD-0228) as the most potent analogue. NPD-0228 has an in vitro pIC₅₀ value of 6.4 against intracellular amastigotes of T. cruzi and no apparent toxicity against the human MRC-5 cell line and murine cardiac cells.     

Development of a Topical Insulin Polymeric Nanoformulation for Skin Burn Regeneration: An Experimental Approach

Insulin is a peptide hormone with many physiological functions, besides its use in diabetes treatment. An important role of insulin is related to the wound healing process—however, insulin itself is too sensitive to the external environment requiring the protective of a nanocarrier. Polymer-based nanoparticles can protect, deliver, and retain the protein in the target area. This study aims to produce and characterize a topical treatment for wound healing consisting of insulin-loaded poly-DL-lactide/glycolide (PLGA) nanoparticles. Insulin-loaded nanoparticles present a mean size of approximately 500 nm and neutral surface charge. Spherical shaped nanoparticles are observed by scanning electron microscopy and confirmed by atomic force microscopy. SDS-PAGE and circular dichroism analysis demonstrated that insulin preserved its integrity and secondary structure after the encapsulation process. In vitro release studies suggested a controlled release profile. Safety of the formulation was confirmed using cell lines, and cell viability was concentration and time-dependent. Preliminary safety in vivo assays also revealed promising results.     

Development and application starch films: PBAT with additives for evaluating the shelf life of Tommy Atkins mango in the fresh-cut state

In this study, formulations of cassava starch and poly(butylene adipate-co-terephthalate) flexible films were developed, with glycerol, coconut nanocellulose, annatto, and citric acid in different concentrations, as well as the effectiveness of the selected materials in fresh-cut mangoes storage was evaluated. The tensile strength of the different formulations varied from 1.90 (E4) to 6.65 MPa (E3c), and the strain varied from 206.31 (E1c) to 278.41% (E8); this variation was dependent on the percentage of the polymer matrix incorporated. The a_w values of the formulations ranged from 0.396 (E2) to 0.569 (E3c). The Formulations E4 and E7 (with additives) presented good properties and were selected to condition mangoes. The micrographs of these films showed regions of micropores that can facilitate the diffusion of water from the packaged product to the surface, allowing decreases in moisture and a_w, which is associated with higher color maintenance during fruit storage. E7 presented better barrier properties than E4 (lower values of WVP and water solubility) which may have influenced in a positive way to maintain the stability of the package in the studied period. E7 can be considered as a viable alternative for minimally processed mango storage. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 48150.     

Challenges for a shared European countryside of uncertain future. Towards a modern community-based landscape perspective

This paper addresses current changes in the highly diverse European landscape, and the way these transitions are being treated in policy and landscape management in the fragmented, heterogeneous and dynamic context of today’s Europe. It appears that intersecting driving forces are increasing the complexity of European landscapes and causing polarising developments in agricultural land use, biodiversity conservation and cultural landscape management. On the one hand, multifunctional rural landscapes, especially in peri-urban regions, provide services and functions that serve the citizens in their demand for identity, support their sense of belonging and offer opportunities for recreation and involvement in practical landscape management. On the other hand, industrial agricultural production on increasingly large farms produces food, feed, fibre and energy to serve expanding international markets with rural liveability and accessibility as a minor issue. The intermediate areas of traditionally dominant small and family farms in Europe seem to be gradually declining in profitability. The paper discusses the potential of a governance approach that can cope with the requirement of optimising land-sharing conditions and community-based landscape development, while adapting to global market conditions.     

Cryptosporidium spp. and Giardia duodenalis in two areas of Galicia (NW Spain)

The aim of the present study was to investigate the environmental dispersal of Cryptosporidium spp. and Giardia duodenalis in two distinct areas (coastal and inland) in Galicia (NW Spain). Faecal samples were collected from healthy asymptomatic domestic (cows and sheep) and wild animals (deer and wild boars) in the selected areas. In each of the selected areas, samples of untreated water (influent) and of treated water (final effluent) were collected from each of the 12 drinking water treatments plants (DWTPs) and 12 wastewater treatment plants (WTPs) under study. Analysis of a single sample from each of the 635 (coastal) and 851 (inland) domestic and wild animals selected at random revealed that the prevalences of cryptosporidiosis and giardiosis in coastal area were 9.2% and 15.9% respectively, and in inland area, 13.7% and 26.7% respectively. In the coastal area, Cryptosporidium spp. oocysts were detected in influent and effluent samples from 2/12 (16.6%) DWTPs and 8/12 (66.6%) WTPs, while G. duodenalis cysts were detected in influent and effluent samples from 3/12 (25.0%) DWTPs and 12/12 (100%) WTPs. The concentrations were notably higher in WTPs; the mean parasite concentrations in the final treated effluent were 10 oocysts per litre and 137.8 cysts per litre for Cryptosporidium and Giardia, respectively. The mean concentration of G. duodenalis cysts per litre was significantly higher (P < 0.05) than the mean concentration of Cryptosporidium spp. oocysts per litre in both the influent and the effluent samples from all the treatment plants. In the coastal area, C. parvum, C. hominis and G. duodenalis assemblages A (I and II) and E were most repeatedly detected. In the inland area, C. parvum, C. andersoni and G. duodenalis assemblages A (I and II), B and E were most frequently identified.     

Preliminary Studies on Furfural Production from Lignocellulosics

This study focused on the production of furfural from agricultural and industrial biomass residues by a hydrodistillation process. Corncobs, sugarcane bagasse, and eucalypt wood were treated with sulfuric, hydrochloric, and phosphoric acids as catalysts, with different acid concentrations (1.5 to 5.2 mol.L ^?1). In addition, the eucalypt liquor from the auto-hydrolysis, kraft-dissolving pulp production process was also investigated as a source of furfural, using sulfuric and hydrochloric acids as a catalyst (0.9 and 3.9 mol.L ^?1) . Furfural yields of 30.2, 25.8, and 13.9% were achieved for corncob, sugarcane bagasse, and eucalypt wood, respectively, on the basis of biomass dry weight. The efficiency of conversion from pentose to furfural using eucalypt liquor from the auto-hydrolysis kraft process was 71.5% using HCl 3.9 mol.L ^?1 . Due to the presence of a high amount of pentose, corncob produced the highest amount of furfural, followed by sugarcane bagasse and then eucalypt wood.