Alternatives for the treatment of schistosomiasis: physico-chemical characterization of an inclusion complex between praziquantel and hydroxypropyl-β-cyclodextrin

O praziquantel (PZQ) é o fármaco de escolha no tratamento da esquistossomose. Porém, ele apresenta baixa solubilidade aquosa, o que pode limitar a sua biodisponibilidade no organismo. Para contornar estas características foi feita a inclusão da molécula do PZQ em hidroxipropil-beta-ciclodextrina (HP-β-CD). Desta forma, o objetivo deste trabalho foi preparar e caracterizar o complexo de inclusão PZQ/HP-β-CD. Estudos morfológicos, espectroscópicos e de calorimetria diferencial de varredura, demonstraram os primeiros indícios da interação hóspede/hospedeiro. Analisando a cinética de incorporação da molécula de PZQ na cavidade da HP-β-CD, pode-se determinar a constante cinética, além do tempo para equilíbrio do sistema. Utilizando-se isoterma de solubilidade foi possível observar que a interação com HP-β-CD aumentou a solubilidade aquosa do PZQ em 2,4 vezes. Ensaios de citotoxicidade in vitro, utilizando fibroblastos, demonstraram não haver indícios de toxicidade para estas células, nas concentrações testadas. Os resultados indicam que há um potencial favorável da aplicação deste fármaco na forma complexada em HP-β-CD.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Gestão por competências em organizações de governo

Ao longo dos últimos anos vem se ampliando os espaços e o interesse, no meio acadêmico e empresarial, pelas discussões sobre uso da abordagem da competência como marco importante para as atividades de gestão de recursos humanos. A difusão dessa abordagem entre as organizações públicas brasileiras é, entretanto, bem mais recente, e conta, ainda hoje, com um número insuficiente de estudos e publicações. É esta a razão da importância e pertinência da publicação do livro " Gestão por competências em organizações de governo"Número de páginas: 100 p.Gestão de PessoasISBN 85-256-0046-

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

A minireview on what we have learned about urease inhibitors of agricultural interest since mid-2000s

World population is expected to reach 9.7 billion by 2050, which makes a great challenge the achievement of food security. The use of urease inhibitors in agricultural practices has long been explored as one of the strategies to guarantee food supply in enough amounts. This is due to the fact that urea, one of the most used nitrogen (N) fertilizers worldwide, rapidly undergoes urease-driven hydrolysis on soil surface yielding up to 70% N losses to environment. This review provides with a compilation of what has been done since 2005 with respect to the search for good urease inhibitors of agricultural interests. The potential of synthetic organic molecules, such as phosphoramidates, hydroquinone, quinones, (di)substituted thioureas, benzothiazoles, coumarin and phenolic aldehyde derivatives, and vanadium-hydrazine complexes, together with B, Cu, S, Zn, ammonium thiosulfate, silver nanoparticles, and oxidized charcoal as urease inhibitors was presented from experiments with purified jack bean urease, different soils and/or plant-soil systems. The ability of some urease inhibitors to mitigate formation of greenhouse gases is also discussed. Keywords: Urease inhibitors, Crop production, Pollution mitigation, Urea, Nitrogen fertilize

Nitric oxide precursors prevent Al-triggered auxin flow inhibition in Triticum aestivum roots

Aluminum (Al) is an element widely distributed in soils, even though Al3+ is one of the most detrimental cations to plant growth. The effect of nitric oxide (NO) precursors on indole-3-acetic acid (IAA) flow towards roots upon Al treatment is herein reported using two Triticum aestivum (wheat) cultivars with recognized differential Al tolerance. Roots of Al-tolerant seedlings with no treatment (control) accumulated higher amounts of NO than Al-sensitive ones. The treatment with Al further stimulated NO production in root cells while root exposure to NO3−, L-arginine (Arg) or the NO donor S-nitrosoglutathione (GSNO) decreased both Al and lipid peroxide accumulation in both cultivars. Regardless of the cultivar, NO3−, Arg or GSNO prevented the blockage of IAA flow towards roots. Overall, the treatment of wheat roots with NO precursors prior to Al treatment effectively guarantees normal IAA flow towards roots, a condition that favors the organ’s growth and development. Keywords: Wheat, Aluminum, Auxin, Nitrate, Arginine, Antioxidant enzyme

Alternativas para o tratamento da esquistossomose: Caracterizacao fisico-quimica do complexo de inclusao entre praziquantel e hidroxipropil-β-ciclodextrina

Praziquantel (PZQ) is the drug of choice commonly used for the treatment of shistosomiasis. However, it has low aqueous solubility, which could limit its bioavailability in the body. To circumvent these features, an inclusion complex with hydroxypropyl-beta- cyclodextrin (HP-β-CD) was prepared. Thus, the objective of this work was to prepare and characterize the PZQ/HP-β-CD inclusion complex. Morphological, spectroscopic, and calorimetric analysis showed the first signs of the guest/host interaction. The complexation kinetic analysis was used to determine the kinetic constant and, besides that, it was possible to establish the time consumed to reach equilibrium. Using the solubility isotherm, it was observed that the interaction with HP-β-CD increased 2.4 fold the aqueous solubility of plain PZQ. In vitro cytotoxicity tests, using fibroblast cells, evidenced no toxicity for these cells at the concentrations tested. These results demonstrated that there is a potential use of PZQ in formulations with HP-β-CD

Exploring natural variation of photosynthetic, primary metabolism and growth parameters in a large panel of Capsicum chinense accessions

Diversity of accessions within the same species provides an alternative method to identify physiological and metabolic traits that have large effects on growth regulation, biomass and fruit production. Here, we investigated physiological and metabolic traits as well as parameters related to plant growth and fruit production of 49 phenotypically diverse pepper accessions of Capsicum chinense grown ex situ under controlled conditions. Although single-trait analysis identified up to seven distinct groups of accessions, working with the whole data set by multivariate analyses allowed the separation of the 49 accessions in three clusters. Using all 23 measured parameters and data from the geographic origin for these accessions, positive correlations between the combined phenotypes and geographic origin were observed, supporting a robust pattern of isolation-by-distance. In addition, we found that fruit set was positively correlated with photosynthesis-related parameters, which, however, do not explain alone the differences in accession susceptibility to fruit abortion. Our results demonstrated that, although the accessions belong to the same species, they exhibit considerable natural intraspecific variation with respect to physiological and metabolic parameters, presenting diverse adaptation mechanisms and being a highly interesting source of information for plant breeders. This study also represents the first study combining photosynthetic, primary metabolism and growth parameters for Capsicum to date

The Role of Pyrazolopyridine Derivatives on Different Steps of Herpes Simplex Virus Type-1 In Vitro Replicative Cycle

Herpes simplex virus type-1 (HSV-1) infection causes several disorders, and acyclovir is used as a reference compound. However, resistant strains are commonly observed. Herein, we investigate the effects of N-heterocyclic compounds (pyrazolopyridine derivatives), named ARA-04, ARA-05, and AM-57, on HSV-1 in vitro replication. We show that the 50% effective concentration (EC50) values of the compounds ARA-04, ARA-05, and AM-57 were 1.00 ± 0.10, 1.00 ± 0.05, and 0.70 ± 0.10 µM, respectively. These compounds presented high 50% cytotoxic concentration (CC50) values, which resulted in a selective index (SI) of 1000, 1000, and 857.1 for ARA-04, ARA-05, and AM-57, respectively. To gain insight into which step of the HSV-1 replication cycle these molecules would impair, we performed adsorption and penetration inhibition assays and time-of-addition experiments. Our results indicated that ARA-04 and ARA-05 affected viral adsorption, while AM-57 interfered with the virus replication during its α- and γ-phases and decreased ICP27 content during initial and late events of HSV-1 replication. In addition, we also observed that AM-57 caused a strong decrease in viral gD content, which was reinforced by in silico calculations that suggested AM-57 interacts preferentially with the viral complex between a general transcription factor and virion protein (TFIIBc-VP16). In contrast, ARA-04 and ARA-05 interact preferentially in the proteins responsible for the viral adsorption process (nectin-1 and glycoprotein). Thus, our results suggest that the 1H-pyrazolo[3,4-b]pyridine derivatives inhibit the HSV-1 replicative cycle with a novel mechanism of action, and its scaffold can be used as a template for the synthesis of promising new molecules with antiviral effects, including to reinforce the presented data herein for a limited number of molecules

Ecofisiologia da germinação de sementes de Campomanesia pubescens Ecophysiology of Campomanesia pubescens seed germination

A gabiroba de arbusto [Campomanesia pubescens (DC.) O. Berg. (Myrtaceae)], espécie nativa do Cerrado é considerada uma planta com potencial melífero, ornamental e medicinal. Com o objetivo de avaliar a influência de diferentes temperaturas, substratos e condições de luminosidade e da secagem, na qualidade fisiológica de suas sementes foram conduzidos dois experimentos. No primeiro utilizou-se sementes com 13% de teor de água, o qual foi realizado em delineamento experimental inteiramente casualizado em esquema fatorial (4x3x2), composto por quatro temperaturas (15-25, 20-30&deg;C alternadas, 25 e 30&deg;C constantes), três substratos (sobre papel, entre areia e entre vermiculita) e duas condições de luminosidade (claro e escuro) e, o segundo com sementes recém extraídas dos frutos e secas superficialmente, contendo 35% de teor de água e após a secagem em estufa com ventilação forçada de ar a temperatura de 30&deg;C por 30, 60, 90, 120, 150, 180, 260, 360, 750 e 810 minutos. Para a avaliação da qualidade fisiológica de sementes de gabiroba de arbusto, a semeadura sobre papel, no escuro e a 30&deg;C possibilita uma melhor expressão do vigor. As sementes de gabiroba de arbusto são intolerantes a secagem, podendo ser classificadas como recalcitrantes.<br>The gabiroba bush [Campomanesia pubescens (DC.) O. Berg. (Myrtaceae)], a native species of the Cerrado is considered a plant with melliferous, ornamental and medicinal potential. Aiming to evaluate the influence of abiotic factors on seed germination, two experiments were conducted. The first was conducted in a completely randomized design in a factorial design(4x3x2), composed of four temperatures (15-25, 20-30&deg;C alternate, 25 and 30&deg;C constant), 3 substrates (paper, sand and vermiculite) and two light conditions (light and dark). The second experiment aimed to evaluate the tolerance to desiccation of fresh seeds dried superficially, with 35% of water, by drying it in oven with forced ventilation of air at 30&deg;C for 30, 60, 90, 120, 150, 180, 260, 360, 750 and 810 minutes. To evaluate the physiological quality of seeds gabiroba, shrub planting on paper, in the dark and 30&deg;C, enables a better expression of the force. The seeds of bush gabiroba are intolerant to desiccation and can be classified as recalcitrant