Theoretical study of the gas-phase reaction between formyl cation and aromatics

Theoretical calculations of the reaction of formyl cation (CHO+) with toluene, cumene and p-cresol showed that proton transfer is thermodynamically preferred over acylation. For toluene, acylation of the aromatic ring, to form the Wheland complex, is 11.7 kcal mol-1 higher in energy (ΔH) than protonation, at MP4(SDTQ)/6-31++G(d,p)//MP2(full)/6-31G(d,p) level of theory. This difference reduces upon introduction of a hydroxy group in the ring (p-cresol) or replacing the methyl group by an isopropyl group (cumene). Protonation of toluene by H3+ and isoformyl cation is 88.6 and 84.5 kcal mol-1, respectively, more exothermic than acylation, at MP4(SDTQ)/6-31++G(d,p)//MP2(full)/6-31G(d,p). The proton affinity of p-cresol was calculated to be 195.4 kcal mol-1

Magnetoliposomes incorporated in peptide-based hydrogels: towards development of magnetolipogels

A major problem with magnetogels is the encapsulation of hydrophobic drugs. Magnetoliposomes not only provide these domains but also improve drug stability and avert the aggregation of the magnetic nanoparticles. In this work, two magnetoliposome architectures, solid and aqueous, were combined with supramolecular peptide-based hydrogels, which are of biomedical interest owing to their biocompatibility, easy tunability, and wide array of applications. This proof-of-concept was carried out through combination of magnetoliposomes (loaded with the model drug curcumin and the lipid probe Nile Red) with the hydrogels prior to pH triggered gelation, and fluorescence spectroscopy was used to assess the dynamics of the encapsulated molecules. These systems allow for the encapsulation of a wider array of drugs. Further, the local environment of the encapsulated molecules after gelation is unaffected by the used magnetoliposome architecture. This system design is promising for future developments on drug delivery as it provides a means to independently modify the components and adapt and optimize the design according to the required conditions.FCT -Fundação para a Ciência e a Tecnologia(UIDB/00686/2020

Molecular diagnostic for levamisol resistance in Haemonchus contortus.

Abstract: In tropical areas, Haemonchus contortus is the leading cause of production losses in small ruminant herds and its control is traditionally done through the utilization of synthetic anthelmintics. Levamisole, an imidazothiazole derivative, is widely used in Brazil and the occurrence of resistance is not uncommon. The genetic base for levamisole resistance in H. contortus is still under investigation, but it has been recently associated with a 63 bp deletion in the Hco-acr-8 gene, which codes for one of the subunits of a levamisole-sensistive acetylcholine receptor. Here we describe a real time PCR test for the detection and quantification of the presence and absence of this deletion. Reactions contained 12.5ul 2 × Fast Start Universal SYBR Green Master Mix (Roche, West Sussex, UK), 0.3 pmol/ul of each primer (forward and reverse), 50 ng of DNA and water for a total volume of 25?l. Amplification conditions for were: 95 oC for 10 min and 35 cycles at 95 oC for 15 s and at 56 ºC for 30 s. We tested the assay in two known H. contortus isolates, one resistant (Kokstad isolate - KOK) and another susceptible (Inbred-susceptible-Edinburgh - ISE). We also used the test to characterize a local H. contortus population previously exposed to levamisole. Preliminay results are in agreement with previously reported data as only the resistant allele was detected in the KOK isolate and both alleles were detected in the ISE isolate suggesting that this test may be useful in the fast detection of levamisole resistance in H. contortus.In conjunction with 53rd MSPTM Annual Conference

DNA Dosimetry Assessment for Sunscreen Genotoxic Photoprotection

Background: Due to the increase of solar ultraviolet radiation (UV) incidence over the last few decades, the use of sunscreen has been widely adopted for skin protection. However, considering the high efficiency of sunlight-induced DNA lesions, it is critical to improve upon the current approaches that are used to evaluate protection factors. An alternative approach to evaluate the photoprotection provided by sunscreens against daily UV radiation-induced DNA damage is provided by the systematic use of a DNA dosimeter. Methodology/Principal Findings: The Sun Protection Factor for DNA (DNA-SPF) is calculated by using specific DNA repair enzymes, and it is defined as the capacity for inhibiting the generation of cyclobutane pyrimidine dimers (CPD) and oxidised DNA bases compared with unprotected control samples. Five different commercial brands of sunscreen were initially evaluated, and further studies extended the analysis to include 17 other products representing various formulations and Sun Protection Factors (SPF). Overall, all of the commercial brands of SPF 30 sunscreens provided sufficient protection against simulated sunlight genotoxicity. In addition, this DNA biosensor was useful for rapidly screening the biological protection properties of the various sunscreen formulations. Conclusions/Significance: The application of the DNA dosimeter is demonstrated as an alternative, complementary, and reliable method for the quantification of sunscreen photoprotection at the level of DNA damage.Natura Inovacao e Tecnologia de Produtos LTDA (Sao Paulo, Brazil)Natura Inovacao e Tecnologia de Produtos LTDA (Sao Paulo, Brazil)FAPESP (Sao Paulo, Brazil)FAPESP (Sao Paulo, Brazil)CNPq (Brasilia, Brazil)CNPq (Brasilia, Brazil)Natura Inovacao e Tecnologia de Produtos LTDANatura Inovacao e Tecnologia de Produtos LTD

An optimized nanoparticle delivery system based on chitosan and chondroitin sulfate molecules reduces the toxicity of amphotericin B and is effective in treating tegumentary leishmaniasis

Amphotericin B (AmpB) is active against leishmaniasis, but its use is hampered due to its high toxicity observed in patients. In this study, a nanoparticles-delivery system for AmpB (NQC-AmpB), containing chitosan and chondroitin sulfate molecules, was evaluated in BALB/c mice against Leishmania amazonensis. An in vivo biodistribution study, including biochemical and toxicological evaluations, was performed to evaluate the toxicity of AmpB. Nanoparticles were radiolabeled with technetium-99m and injected in mice. The products presented a similar biodistribution in the liver, spleen, and kidneys of the animals. Free AmpB induced alterations in the body weight of the mice, which, in the biochemical analysis, indicated hepatic and renal injury, as well as morphological damage to the kidneys of the animals. In general, no significant organic alteration was observed in the animals treated with NQC-AmpB. Mice were infected with L. amazonensis and treated with the nanoparticles or free AmpB; then, parasitological and immunological analyses were performed. The NQC-AmpB group, as compared to the control groups, presented significant reductions in the lesion size and in the parasite burden in all evaluated organs. These animals presented significantly higher levels of IFN-γ and IL-12, and low levels of IL-4 and IL-10, when compared to the control groups. The NQC-AmpB system was effective in reducing the infection in the animals, and proved to be effective in diminishing the toxicity evoked by AmpB, which was observed when it was administered alone. In conclusion, NQC-AmpB could be considered a viable possibility for future studies in the treatment of leishmaniasisThis work was supported by grants from Pró-Reitoria de Pesquisa from UFMG (Edital 01/2014), Instituto Nacional de Ciência e Tecnologia em Nano-biofarmacêutica (INCT-Nanobiofar), FAPEMIG (CBB-APQ-00496-11 and CBB-APQ-00819-12), and CNPq (APQ-472090/2011-9 and APQ-482976/2012-8). MACF is a grant recipient of FAPEMIG/CAPES. EAFC, VNC, and AAGF are grant recipients of CNPq. Eduardo AF Coelho and André AG Faraco are co-senior authors of this stud

Nycthemeral and Monthly Occupation of the Fish Assemblage on a Sheltered Beach of Baía Norte, Florianópolis, Santa Catarina State, Brazil

Interpreting fish community records is challenging for several reasons, including the lack of past ichthyofauna data, the cyclical temporal variations in the community, and the methodology employed, which usually underestimates fish assemblages. The objective of this study was to describe short-scale and meso-scale (nycthemeral period and months, respectively) temporal variations in the ichthyofauna composition and structure of a sheltered beach of Baía Norte (Florianópolis, Santa Catarina state, Brazil), using a capéchade net. Samples were collected monthly for a period of 48 hours. During the period from December 2010 to November 2011, a total of 19,302 individuals belonging to 89 species and 39 families were captured. The number of individuals that were sampled during the day and/or night was dependent on the sampling month. On average, the daytime assemblage was more abundant and different in structure and composition than the nighttime assemblage. Of the eight species that had the highest Index of Relative Importance (%IRI), five had higher variations (ANOVA F) between the day and night than between the months. This finding reinforced the need for sampling during both the day and night. The capéchade net effectively captured demersal and pelagic individuals in a broad range of sizes

Self-Reactivities to the Non-Erythroid Alpha Spectrin Correlate with Cerebral Malaria in Gabonese Children

BACKGROUND: Hypergammaglobulinemia and polyclonal B-cell activation commonly occur in Plasmodium sp. infections. Some of the antibodies produced recognize self-components and are correlated with disease severity in P. falciparum malaria. However, it is not known whether some self-reactive antibodies produced during P. falciparum infection contribute to the events leading to cerebral malaria (CM). We show here a correlation between self-antibody responses to a human brain protein and high levels of circulating TNF alpha (TNFα), with the manifestation of CM in Gabonese children. METHODOLOGY: To study the role of self-reactive antibodies associated to the development of P. falciparum cerebral malaria, we used a combination of quantitative immunoblotting and multivariate analysis to analyse correlation between the reactivity of circulating IgG with a human brain protein extract and TNFα concentrations in cohorts of uninfected controls (UI) and P. falciparum-infected Gabonese children developing uncomplicated malaria (UM), severe non-cerebral malaria (SNCM), or CM. RESULTS/CONCLUSION: The repertoire of brain antigens recognized by plasma IgGs was more diverse in infected than in UI individuals. Anti-brain reactivity was significantly higher in the CM group than in the UM and SNCM groups. IgG self-reactivity to brain antigens was also correlated with plasma IgG levels and age. We found that 90% of CM patients displayed reactivity to a high-molecular mass band containing the spectrin non-erythroid alpha chain. Reactivity with this band was correlated with high TNFα concentrations in CM patients. These results strongly suggest that an antibody response to brain antigens induced by P. falciparum infection may be associated with pathogenic mechanisms in patients developing CM