149 research outputs found

    Chemical and pharmacological investigation of Solanum species of Brazil: a search for solasodine and other potentially useful therapeutic agents

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    A systematic search for solasodine, an important staring material for the partial synthesis of steroidal hormones as well as other potentially bioactive constituents of various Solanum species of Brazil has been undertaken. Thus, the fruits of S. paludosum, S. asperum, S. sessiliforum and Solanum sp. were found to contain significant amounts of solasodine. The root bark of S. paludosum which showe durare like activity yelded tomatidenol and another yet unidentified alkaloid responsible for the biological activity. The fruits of S. asperum yelded a new spirosolane alkaloid, solaparnaine. The stem bark of S. pseudo-quina showed convulsive and exitatory activity from which (25S)-isosolafloridine was identified as the active principle. In addition, the latter alkaloid was also found to show antimicrobial activity

    Curcumin encapsulation in nanostructures for cancer therapy: a 10-year overview

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    Journal pre-proofsCurcumin (CUR) is a phenolic compound present in some herbs, including Curcuma longa Linn. (turmeric rhizome), with a high bioactive capacity and characteristic yellow color. It is mainly used as a spice, although it has been found that CUR has interesting pharmaceutical properties, acting as a natural antioxidant, anti-inflammatory, antimicrobial, and antitumoral agent. Nonetheless, CUR is a hydrophobic compound with low water solubility, poor chemical stability, and fast metabolism, limiting its use as a pharmacological compound. Smart drug delivery systems (DDS) have been used to overcome its low bioavailability and improve its stability. The current work overviews the literature from the past 10 years on the encapsulation of CUR in nanostructured systems, such as micelles, liposomes, niosomes, nanoemulsions, hydrogels, and nanocomplexes, emphasizing its use and ability in cancer therapy. The studies highlighted in this review have shown that these nanoformulations achieved higher solubility, improved tumor cytotoxicity, prolonged CUR release, and reduced side effects, among other interesting advantages.This study was funded by the Coordination for Higher Level Graduate Improvements (CAPES/Brazil, finance code 001), National Council for Scientific and Technological Development (CNPq/Brazil, PIBIC process #123483/2020-4), State of São Paulo Research Foundation (FAPESP/Brazil, processes #2017/10789-1, #2018/10799-0, #2018/06475-4, #2018/07707-6, #2019/08549-8, and #2020/03727-2). This work was also supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UIDB/04469/2020 unit and the project AgriFood XXI (NORTE-01-0145-FEDER-000041) funded by the European Regional Development Fund under the scope of Norte2020 - Programa Operacional Regional do Norte. Our Figures were created with BioRenderinfo:eu-repo/semantics/publishedVersio

    Immunisation with Recombinant PfEMP1 Domains Elicits Functional Rosette-Inhibiting and Phagocytosis-Inducing Antibodies to Plasmodium falciparum

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    BACKGROUND: Rosetting is a Plasmodium falciparum virulence factor implicated in the pathogenesis of life-threatening malaria. Rosetting occurs when parasite-derived P. falciparum Erythrocyte Membrane Protein One (PfEMP1) on the surface of infected erythrocytes binds to human receptors on uninfected erythrocytes. PfEMP1 is a possible target for a vaccine to induce antibodies to inhibit rosetting and prevent severe malaria. METHODOLOGY/FINDINGS: We examined the vaccine potential of the six extracellular domains of a rosette-mediating PfEMP1 variant (ITvar9/R29var1 from the R29 parasite strain) by immunizing rabbits with recombinant proteins expressed in E. coli. Antibodies raised to each domain were tested for surface fluorescence with live infected erythrocytes, rosette inhibition and phagocytosis-induction. Antibodies to all PfEMP1 domains recognized the surface of live infected erythrocytes down to low concentrations (0.02-1.56 µg/ml of total IgG). Antibodies to all PfEMP1 domains except for the second Duffy-Binding-Like region inhibited rosetting (50% inhibitory concentration 0.04-4 µg/ml) and were able to opsonize and induce phagocytosis of infected erythrocytes at low concentrations (1.56-6.25 µg/ml). Antibodies to the N-terminal region (NTS-DBL1α) were the most effective in all assays. All antibodies were specific for the R29 parasite strain, and showed no functional activity against five other rosetting strains. CONCLUSIONS/SIGNIFICANCE: These results are encouraging for vaccine development as they show that potent antibodies can be generated to recombinant PfEMP1 domains that will inhibit rosetting and induce phagocytosis of infected erythrocytes. However, further work is needed on rosetting mechanisms and cross-reactivity in field isolates to define a set of PfEMP1 variants that could induce functional antibodies against a broad range of P. falciparum rosetting parasites

    Índice de anomalia de chuva (IAC) e sua relação com os desastres naturais no leste da Amazônia.

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    O presente trabalho faz um estudo sobre os Índices de Anomalia de Chuva (IAC) e suas relações com os desastres naturais na cidade de Marabá no sudeste do Pará, Amazônia Oriental. Foram usados dados de precipitação pluviométrica média mensal dos anos de 1973 a 2017 da cidade de Marabá, oriundos do Instituto Brasileiro de Meteorologia (INMET), dados de informações básicas a respeito da Gestão de Riscos e Desastres Naturais da região de Marabá. Estes dados foram obtidos por meio do Instituto Brasileiro de Geografia e Estatística (IBGE), e dados simulados de precipitação do modelo climático Coupled Climate Mode 3. Utilizou-se estatística básica e também a metodologia do próprio IAC, que é uma metodologia eficaz, direta e simples. Desta forma, foi possível obter os índices de anomalias negativas (secas) e positivas (cheias). O resultado dos índices foi divido em três categorias ou intensidades: Fraco (FRA), Moderado (MOD) e Forte (FOR). Para a climatologia da região, março indicou ser o mês mais chuvoso, e o mês mais seco ficou com agosto. O maior volume de chuva ficou com o mês de março e em abril os volumes de chuva começaram a diminuir, atingindo menor valor em agosto, e em setembro os volumes precipitantes começaram a aumentar. Os trimestres mais chuvosos são dezembro, janeiro e fevereiro (DJF) e março, abril e maio (MAM). O trimestre mais seco ficou com junho, julho e agosto (JJA), e em setembro, outubro e novembro (SON) os volumes de chuva começam a aumentar. As ocorrências de EL Niño e La Niña tiveram total relação com os resultados encontrados pelo IAC. Pois em todos os anos de ocorrência de EL Niño ou La Niña, se observou a presença da categoria FOR. Os resultados mostraram que os eventos mais relevantes para as anomalias negativas, encontram-se na categoria FRA e MOD, sendo que estas duas categorias ficaram praticamente equivalentes. E estes resultados, não tiveram relação com as informações da gestão de risco e desastre do local estudado. Para as anomalias positivas, os resultados mostraram que os eventos mais relevantes, encontram-se na categoria MOD, indicando que a região de Marabá é caracterizada por um ambiente chuvoso, e esta caracterização teve total relação com os eventos da gestão de risco e desastre ocorridos em Marabá. Vale ressaltar que o cenário futuro encontrado por meio das simulações, comprovou ser uma intensificação dos atuais padrões de tempo e clima da cidade de Marabá. E de acordo com os noticiários deste ano de 2020, Marabá já está sofrendo com enchentes. Desta forma, o IAC é uma ótima ferramenta para caracterização climatológica e alerta de possíveis áreas de risco

    Variação do CO2 atmosférico e do efluxo de CO2 do solo em iPF na Amazônia.

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    O estudo teve como objetivo quantificar a concentração de dióxido de carbono (CO2) na atmosfera ([CO2]) e estimar o efluxo de CO2 do solo (Esolo) em um sistema de integração pecuária-floresta (iPF) no leste da Amazônia. Campanhas intensivas de 24 horas de medidas foram conduzidas nos períodos: (i) menos chuvoso de 2016, 2017 e 2018; (ii) chuvoso de 2017 e 2018, e, (iii) transição do chuvoso para menos chuvoso de 2017 e 2018, no município de Terra Alta, nordeste do Pará. Sistema de medição da [CO2] foram instalados em espécies florestais e na pastagem, e pontos no renque florestal e pastagem foram selecionados para a medição do Esolo. Uma torre meteorológica automática foi instalada na área para a obtenção de dados ancilares. A [CO2] apresentou variação temporal com menores valores durante o dia e maiores durante a noite. Houve maior [CO2] no período chuvoso e na transição do período chuvoso para menos chuvoso comparado ao menos chuvoso. O Esolo foi maior no interior do renque florestal e apresentou as maiores medidas no mesmo período que a [CO2]. A velocidade do vento e Esolo atuam de maneira diferente sobre a [CO2] a depender do período

    Strategies for Multiplexed Electrochemical Sensor Development

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    Detection of multiple biomarkers for disease diagnosis or treatment monitoring has received a lot of attention due to their potential impact on clinical decision making. Electrochemical biosensors have become one of the preferred detection approaches, due to the simplicity of the accompanying instrumentation. This chapter will explore how electrochemical sensors can be utilized for detection of multiple analytes by integration of sensors into microfluidic microsystems. Some key fabrication technologies for such devices will be presented utilizing polymer microfabrication, paper-based approaches, and the use of printed circuit boards. Next, the use of electrode arrays will be presented along with some commercial platforms, outlining plausible paths towards a successful electrochemical multiplexed sensor. Novel approaches based on microbeads and various labels will then be introduced along with various strategies and technologies utilized to achieve ultrasensitive multiplexed detection

    Elective surgery cancellations due to the COVID-19 pandemic: global predictive modelling to inform surgical recovery plans.

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    BACKGROUND: The COVID-19 pandemic has disrupted routine hospital services globally. This study estimated the total number of adult elective operations that would be cancelled worldwide during the 12 weeks of peak disruption due to COVID-19. METHODS: A global expert response study was conducted to elicit projections for the proportion of elective surgery that would be cancelled or postponed during the 12 weeks of peak disruption. A Bayesian β-regression model was used to estimate 12-week cancellation rates for 190 countries. Elective surgical case-mix data, stratified by specialty and indication (surgery for cancer versus benign disease), were determined. This case mix was applied to country-level surgical volumes. The 12-week cancellation rates were then applied to these figures to calculate the total number of cancelled operations. RESULTS: The best estimate was that 28 404 603 operations would be cancelled or postponed during the peak 12 weeks of disruption due to COVID-19 (2 367 050 operations per week). Most would be operations for benign disease (90·2 per cent, 25 638 922 of 28 404 603). The overall 12-week cancellation rate would be 72·3 per cent. Globally, 81·7 per cent of operations for benign conditions (25 638 922 of 31 378 062), 37·7 per cent of cancer operations (2 324 070 of 6 162 311) and 25·4 per cent of elective caesarean sections (441 611 of 1 735 483) would be cancelled or postponed. If countries increased their normal surgical volume by 20 per cent after the pandemic, it would take a median of 45 weeks to clear the backlog of operations resulting from COVID-19 disruption. CONCLUSION: A very large number of operations will be cancelled or postponed owing to disruption caused by COVID-19. Governments should mitigate against this major burden on patients by developing recovery plans and implementing strategies to restore surgical activity safely

    Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

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    Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised
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