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Salinity is harmful to crops when the concentration of soluble salts overcomes the salinity threshold of the crop, causing osmotic stress and limitations in plant growth. In this scenario, adopting tolerant cultivars is the most adequate strategy to minimize agricultural losses. However, the inheritance of tolerance depends on the genotype. From this perspective, this study assessed the tolerance to severe salt stress in 11 cotton cultivars based on gas exchange parameters and the free proline content. The cultivars were grown in a greenhouse and subjected to 34 days of saline irrigation (10 dS m-1), starting 45 days after seedling emergence (B1 phase). Plant growth was monitored weekly until the end of the salt stress period. The treatments consisted of a combination of two factors: eleven cultivars associated with two electrical conductivity levels of irrigation water (ECw: 0.3 and 10.0 dS m-1). The experimental design was in randomized blocks in a 11 × 2 factorial arrangement with three replications (66 plots), with the experimental unit consisting of one plant per plot. Salinity impacted plant growth, being reflected on the gas exchange and free proline data of most cultivars. However, BRS 286, FMT 705, BRS 416, and BRS Acácia, and CNPA 7MH withstood the effects of stress and osmotically adjusted to the salt stress conditions, thus minimizing the damage to growth. Those cultivars are the most indicated for improvement programs aiming at tolerance to salt stress based on the results found in this research.
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Estrés Salino , Tolerancia a la Sal , Plantones , Salinidad , ProlinaRESUMEN
Marine sponges from the Plakinidae family are well known for hosting cytotoxic secondary metabolites and the Brazilian Atlantic coast and its oceanic islands have been considered as a hotspot for the discovery of new Plakinidae species. Herein, we report the chemical profile among cytotoxic extracts obtained from four species of Plakinidae, collected in Fernando de Noronha Archipelago (PE, Northeastern Brazil). Crude organic extracts of Plakinastrella microspiculifera, Plakortis angulospiculatus, Plakortis insularis, and Plakortis petrupaulensis showed strong antiproliferative effects against two different cancer cell lines (HCT-116: 86.7-100%; MCF-7: 74.9-89.5%) at 50 µg/mL, by the MTT assay. However, at a lower concentration (5 µg/mL), high variability in inhibition of cell growth was observed (HCT-116: 17.3-68.7%; MCF-7: 0.00-55.5%), even within two samples of Plakortis insularis which were collected in the west and east sides of the Archipelago. To discriminate the chemical profile, the samples were investigated by UHPLC-HRMS under positive ionization mode. The produced data was uploaded to the Global Natural Products Social Molecular Networking and organized based on spectral similarities for purposes of comparison and annotation. Compounds such as dipeptides, nucleosides and derivatives, polyketides, and thiazine alkaloids were annotated and metabolomic differences were perceived among the species. To the best of our knowledge, this is the first assessment for cytotoxic activity and chemical profiling for Plakinastrella microspiculifera, Plakortis insularis and Plakortis petrupaulensis, revealing other biotechnologically relevant members of the Plakinidae family.
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Metaboloma , Poríferos/química , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Productos Biológicos/química , Productos Biológicos/farmacología , Brasil , Proliferación Celular/efectos de los fármacos , Células HCT116 , Humanos , Islas , Células MCF-7 , Metabolómica , Neoplasias/tratamiento farmacológico , Plakortis/química , Plakortis/metabolismo , Poríferos/metabolismoRESUMEN
This work reports an analytical method for determining electrical resistivity (ρ) and sheet resistance (RS) of isotropic conductors. The method is compared with previous numerical solutions and available experimental data showing a universal behavior for isotropic conductors. An approximated solution is also reported allowing one to easily determine ρ and RS for samples either with regular or arbitrary shapes.
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INTRODUCTION: Cryptococcus neoformans is an opportunistic pathogen that causes â¼15% mortality in AIDS patients. Rio Grande City, Rio Grande do Sul (RS), Brazil, has the highest national rate of HIV/AIDS, considering cities with population more than 100,000 habitants. OBJECTIVE: We aimed to evaluate the clinical and epidemiological profile of cryptococcosis in a reference service for HIV-AIDS patients in the South region of Brazil, over seven years. Material and methods A retrospective study was performed including all cryptococcosis cases diagnosed at the University Hospital, Federal University of Rio Grande (UH-FURG) between January 2010 and December 2016. RESULTS: Seventy cases of cryptococcosis were diagnosis from 2010 to 2016 in the UH-FURG in the seven years of the study. These numbers were responsible for 2.1% to 8.1% of the hospitalizations/year for HIV patients. All were caused by C. neoformans infection (95% C. neoformans var. grubii VNI and 5% C. neoformans var. grubii VNII). Neurocryptococcosis was the major clinical manifestation and cryptococcosis was the HIV- defining condition in 40% of patients. The period of hospitalization was an average of 39.3 days (SD=31.3), and more than half of patients (53%; 37/70) died after a mean of 82 days. DISCUSSION: The present study showed the importance of cryptococcosis as an AIDS-defining disease in HIV-AIDS patients in a tertiary hospital from Southern Brazil. More investment is necessary to reduce the impact of this opportunistic mycosis in HIV-AIDS patients from southern Brazil.
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Infecciones Oportunistas Relacionadas con el SIDA/epidemiología , Síndrome de Inmunodeficiencia Adquirida/epidemiología , Criptococosis/epidemiología , Infecciones por VIH/epidemiología , Infecciones Oportunistas Relacionadas con el SIDA/microbiología , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Síndrome de Inmunodeficiencia Adquirida/microbiología , Adulto , Anciano , Brasil/epidemiología , Criptococosis/complicaciones , Criptococosis/microbiología , Cryptococcus neoformans/aislamiento & purificación , Femenino , VIH , Infecciones por VIH/complicaciones , Infecciones por VIH/microbiología , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Meningitis Fúngica/epidemiología , Meningitis Fúngica/etiología , Meningitis Fúngica/microbiología , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos , Análisis de Supervivencia , Adulto JovenRESUMEN
We present surveys of derbid planthoppers associated with coconut (Cocos nucifera L.) and oil palm (Elaeis guineensis Jacq.) collected in Northeastern (Sergipe) and North (Pará and Roraima) Brazil. The surveys were intended to contribute to our knowledge of possible vectors of phytoplasmas or other phloem-restricted plant pathogens. Eight derbid taxa were found, two in the subfamily Cedusinae, tribe Cedusini (Cedusa yipara Kramer and C. yowza Kramer) and six in the subfamily Derbinae, tribe Cenchreini: Herpis sp., Persis pugnax Stål, Omolicna anastomosa (Caldwell), O. nigripennis (Caldwell), and two new species in the genus Agoo Bahder & Bartlett are described here. Genus-level features between Omolicna and Agoo are discussed and a key to the species of Agoo is provided.
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Arecaceae , Cocos , Hemípteros/anatomía & histología , Hemípteros/clasificación , Animales , Brasil , Femenino , Insectos Vectores/anatomía & histología , Insectos Vectores/clasificación , Masculino , PhytoplasmaRESUMEN
Nowadays, boron nitride has attracted a great deal of attention due to its physical (chemical) properties, facile synthesis, and experimental characterization, indicating great potential for industrial application. Based on this, we develop here a theoretical study on boron nitride nanoflakes built-up from hexagonal boron nitride nanosheets exhibiting hexagonal, rectangular, and triangular shapes. In order to investigate geometry effects such as those due to the presence of armchair and zigzag edges and distinct shapes, we analyzed their properties from both classical and quantum viewpoints. Using classical molecular dynamics calculations, we show that the nanosheets preserve their structural stability at high temperatures, while DFT calculations demonstrate HOMO-LUMO energy gap variation within the theoretical energy gaps of h-BN in bulk and 2D crystals. Besides that, we have also found that boron nitride nanoflakes structures have spatially symmetrical spin densities.
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New therapeutic approaches are necessary to control strongyloidiasis due to the side effects of, and resistance to, currently available drugs thiabendazole, albendazole, and ivermectin. This study examined the anthelmintic properties of extracts and isolated compounds from Siparuna guianensis against Strongyloides venezuelensis eggs and larvae, using the egg hatching test (EHT) and larval motility test (LMT). Albendazole (0.025 mg/ml) and ivermectin (0.316 mg/ml) were used as the positive controls for the EHT and LMT assays, respectively. Strongyloides venezuelensis eggs or larvae (±50 specimens) were treated with ethanol extract (0.05-1.0 mg/ml), ethyl acetate and aqueous fractions (0.05-0.8 mg/ml), essential oil (0.2-1.0 mg/ml) and α-bisabolol (0.2-1.0 mg/ml) from S. guianensis, and analysed by optical microscopy after 48 h (EHT), or after 24, 48 and 72 h (LMT). All the tested compounds exhibited ovicidal activity equivalent to the positive control and changed the morphology of the eggs. The S. guianensis ethanol extract and aqueous fraction were as effective as the positive control. Phytochemical analysis of the ethanol extract and fractions revealed the presence of phenolic compounds, tannins and flavonoids. Therefore, S. guianensis is effective against S. venezuelensis eggs and larvae in vitro, and can be considered as a potential alternative treatment for strongyloidiasis.
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Antihelmínticos/farmacología , Aceites Volátiles/farmacología , Extractos Vegetales/farmacología , Strongyloides/efectos de los fármacos , Tracheophyta/química , Animales , Antihelmínticos/química , Larva/efectos de los fármacos , Sesquiterpenos Monocíclicos/química , Sesquiterpenos Monocíclicos/farmacología , Aceites Volátiles/química , Óvulo/efectos de los fármacos , Extractos Vegetales/químicaRESUMEN
Essential oils (EO) are volatile liquids responsible for the aroma of plants. Pterodon polygalaeflorus seeds have received widespread use in folk medicine for the treatment of inflammatory diseases. For this reason and because Pterodon polygalaeflorus seeds have great EO content, which is frequently pharmacologically active, the present study aimed to evaluate the antinociceptive effect of EO from Pterodon polygalaeflorus (EOPPgfl) and its acute toxic effects. The EEOPPgfl sample, which was extracted by steam distillation of the seeds, had a yield of 2.4% of the seeds weight and had, as major constituents, beta-elemene (48.19%), trans-caryophyllene (19.51%), and epi-bicyclosesquiphellandrene (12.24%). The EOPPgfl sample showed mild acute toxicity and its calculated median lethal dose (LD50) was 3.38 g/kg. EOPPgfl (20-60 mg/kg) showed antinociceptive activity as evidenced by several tests and inhibited writhing induced by acetic acid. The maximum effect was obtained with the 30 mg/kg dose and at 60 min after its administration. EOPPgfl also decreased formalin-induced nociception, as verified by the inhibition of the first and second phase of the formalin test. At 30 mg/kg, EOPPgfl also decreased thermally stimulated nociception. Nociception may be related to inflammatory and antiedematogenic activity and at doses ranging 10-100 mg/kg, EOPPgfl blocked dextran- and carrageenan-induced edema. The results demonstrated that EOPPgfl presented, at doses approximately 100 times smaller than LD50, an antinociceptive effect that probably was due to anti-inflammatory activities.
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Analgésicos/farmacología , Fabaceae/química , Nocicepción/efectos de los fármacos , Aceites Volátiles/farmacología , Extractos Vegetales/farmacología , Aceites de Plantas/farmacología , Animales , Antiinflamatorios/farmacología , Ratones , Dimensión del Dolor , Distribución Aleatoria , Reproducibilidad de los Resultados , Semillas/química , Factores de Tiempo , Resultado del TratamientoRESUMEN
Papillomaviruses (PVs) are complex viruses which infect the skin or mucosae of a broad range of amniotes worldwide. They cause benign or malignant lesions depending on environmental factors, virus oncogenicity and the location of infection. Bovine papillomaviruses (BPVs) are the second most studied PVs beyond human PVs. In the past few years, genetic characterization of animal PVs has increased due to the availability of new techniques, which simplified the sequencing of entire genomes. Therefore, this review aims to provide an update of the current epidemiology, classification and genome features of ruminant PVs (mainly BPVs) affecting animals worldwide. The review also aimed to clarify the key differences between the high-risk Delta papillomaviruses and the seemingly low-risk Xi, Epsilon, Dyoxi and Dyokappapillomavirus as well as the recently described PVs BPV18, 19, 21 and PpuPV1 that belongs to an unclassified genus.
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Enfermedades de los Bovinos/virología , Papillomaviridae , Infecciones por Papillomavirus/virología , Rumiantes/virología , Animales , Bovinos , Enfermedades de los Bovinos/epidemiología , Humanos , Papillomaviridae/clasificación , Papillomaviridae/genética , Infecciones por Papillomavirus/clasificación , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/genética , Filogenia , Estructuras Virales/fisiologíaRESUMEN
Essential oils (EO) are volatile liquids responsible for the aroma of plants. Pterodon polygalaeflorus seeds have received widespread use in folk medicine for the treatment of inflammatory diseases. For this reason and because Pterodon polygalaeflorus seeds have great EO content, which is frequently pharmacologically active, the present study aimed to evaluate the antinociceptive effect of EO from Pterodon polygalaeflorus (EOPPgfl) and its acute toxic effects. The EEOPPgfl sample, which was extracted by steam distillation of the seeds, had a yield of 2.4% of the seeds weight and had, as major constituents, beta-elemene (48.19%), trans-caryophyllene (19.51%), and epi-bicyclosesquiphellandrene (12.24%). The EOPPgfl sample showed mild acute toxicity and its calculated median lethal dose (LD50) was 3.38 g/kg. EOPPgfl (20-60 mg/kg) showed antinociceptive activity as evidenced by several tests and inhibited writhing induced by acetic acid. The maximum effect was obtained with the 30 mg/kg dose and at 60 min after its administration. EOPPgfl also decreased formalin-induced nociception, as verified by the inhibition of the first and second phase of the formalin test. At 30 mg/kg, EOPPgfl also decreased thermally stimulated nociception. Nociception may be related to inflammatory and antiedematogenic activity and at doses ranging 10-100 mg/kg, EOPPgfl blocked dextran- and carrageenan-induced edema. The results demonstrated that EOPPgfl presented, at doses approximately 100 times smaller than LD50, an antinociceptive effect that probably was due to anti-inflammatory activities.
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Animales , Conejos , Aceites de Plantas/farmacología , Aceites Volátiles/farmacología , Extractos Vegetales/farmacología , Nocicepción/efectos de los fármacos , Analgésicos/farmacología , Fabaceae/química , Semillas/química , Factores de Tiempo , Dimensión del Dolor , Distribución Aleatoria , Reproducibilidad de los Resultados , Resultado del Tratamiento , Antiinflamatorios/farmacologíaRESUMEN
Background Around the world, people receive care at various institutions; therefore, clinical information is recorded either on paper or distributed on different information systems with reduced capabilities for sharing data. One approach to handling the complex nature of the health information systems and making it interoperable is the two-level modeling, and the ISO 13606 standard is an option to support this model. A regionally governed EHR program in Brazil proposed to use the ISO 13606 standard and archetypes. This program includes an EHR repository for consolidating the longitudinal electronic record of patients' health. Objective This article aims to present the results and lessons learned from a proof-of-concept (POC) for integrating the Maternal and Neonatal Healthcare Information System (SISMater) developed by the Federal University of Minas Gerais (UFMG) with the EHR system developed by the Department of Healthcare for the State of Minas Gerais (SES/MG). Methods The design of the architecture and software development were driven by the content to be exchanged between the SISMater system and the EHR system and the usage of XML transformation to translate an ISO 13606 EHR extract and vice versa. This POC did not include tests related to revision objects according to ISO 13606 reference model. Results The software architecture and software components required for this POC were proposed and tested. The EHR system validated the syntax and semantic and persisted the extract in the EHR repository. Complete results can be accessed at https://github.com/pocppsus/repository. Conclusion The approach for using XML transformations could make easier the process for ISO 13606 noncompliant EMR systems to exchange EHR data with the SES/MG EHR system.
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Atención a la Salud/normas , Intercambio de Información en Salud/normas , Madres , Femenino , Humanos , Recién Nacido , Modelos Estadísticos , Embarazo , Estándares de ReferenciaRESUMEN
Lippia sidoides Cham is a typical herb species of Northeast Brazil with widespread use in folk medicine. The major constituents of the essential oil of L. sidoides (EOLs) are thymol, p-cymene, myrcene, and caryophyllene. Several studies have shown that the EOLs and its constituents have pharmacological effects, including antibacterial, anti-inflammatory, antioxidant and neuroprotective activity. Therefore, this work aimed to investigate the effects of the EOLs and their main constituents on rat sciatic nerve excitability. The sciatic nerves of adult Wistar rats were dissected and mounted in a moist chamber. Nerves were stimulated by square wave pulses, with an amplitude of 40 V, duration of 100 µs to 0.2 Hz. Both EOLs and thymol inhibited compound action potential (CAP) in a concentration-dependent manner. Half maximal inhibitory concentration for CAP peak-to-peak amplitude blockade were 67.85 and 40 µg/mL for EOLs and thymol, respectively. CAP peak-to-peak amplitude was significantly reduced by concentrations ≥60 µg/mL for EOLs and ≥30 µg/mL for thymol. EOLs and thymol in the concentration of 60 µg/mL significantly increased chronaxie and rheobase. The conduction velocities of 1st and 2nd CAP components were also concentration-dependently reduced by EOLs and thymol in the range of 30-100 µg/mL. Differently from EOLs and thymol, p-cymene, myrcene and caryophyllene did not reduce CAP in the higher concentrations of 10 mM. These data demonstrated that EOLs and thymol inhibited neuronal excitability and were promising agents for the development of new drugs for therapeutic use.
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Alquenos/farmacología , Lippia/química , Monoterpenos/farmacología , Aceites Volátiles/farmacología , Nervio Ciático/efectos de los fármacos , Sesquiterpenos/farmacología , Timol/farmacología , Potenciales de Acción/efectos de los fármacos , Potenciales de Acción/fisiología , Monoterpenos Acíclicos , Animales , Cimenos , Femenino , Masculino , Bloqueo Nervioso/métodos , Conducción Nerviosa/efectos de los fármacos , Aceites Volátiles/química , Sesquiterpenos Policíclicos , Ratas Wistar , Reproducibilidad de los Resultados , Nervio Ciático/fisiología , Factores de TiempoRESUMEN
BACKGROUND: Intensive prophylactic use of antifungals leads to the increase of drug resistance and the need for new and more effective treatments are real. Plants from Leguminosae family are rich in flavonoids, for which numerous biological activities have been described, including antifungal effects. PURPOSE: To screen methanolic extracts from Leguminosae species looking for alternative sources for antifungal agents (anti-dermatophyte and anti-Candida) and their innocuity. METHODS: Antifungal activity was evaluated using the strains Candida albicans, C. krusei, C. glabrata, C. tropicalis, C. parapsilosis, Epidermophyton floccosum, Trichophyton mentagrophytes, T. rubrum and, Microsporum gypseum in the broth microdilution method. Later, the minimum inhibitory concentration (MIC) for Mimosa pigra, Eriosema heterophyllum, and Chamaecrista nictitans was determined. The most promising extract was fractionated and cytotoxicity and genotoxicity of the most active fraction were also assayed. RESULTS: Fungicide and/or fungistatic activity against dermatophyte strains were presented by 60% of the methanolic extracts assayed. M. pigra, E. heterophyllum, and C. nictitans methanolic extracts could inhibit dermatophyte strains at concentrations ranging from 1.9 to 1000µg/mL. M. pigra showed the lowest MIC values for a dichloromethane fraction (1.9µg/mL) without DNA damage at 10 and 50µg/mL and 100% of cell viability of human leukocytes. CONCLUSION: Our results indicate that methanolic extracts from Leguminosae plants are potential sources of antifungal compounds, mainly the extract and fractions from M. pigra. The dichloromethane fraction from M. pigra did not showed in vitro toxicity according to the applied assays.
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Antifúngicos/farmacología , Arthrodermataceae/efectos de los fármacos , Fabaceae/química , Mimosa/química , Extractos Vegetales/farmacología , Brasil , Candida/efectos de los fármacos , Epidermophyton/efectos de los fármacos , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Microsporum/efectos de los fármacos , Pruebas de Toxicidad , Trichophyton/efectos de los fármacosRESUMEN
BACKGROUND AND OBJECTIVE: Periodontitis may promote harmful systemic effects such as changes in hepatic tissues. The purpose of this study was to investigate whether the steatosis and oxidative stress caused by experimental periodontitis are reversible in the liver. MATERIAL AND METHODS: Twenty-four rats were divided into three groups: control, periodontitis and P20-20 (20 days with experimental periodontitis and 20 days without experimental periodontitis, to verify the reversibility of hepatic injuries). The following parameters were assessed: gingival bleeding index, probing pocket depth, myeloperoxidase activity, alveolar bone loss for periodontal tissues; liver weights, histopathological scores for steatosis, inflammation and necrosis in liver; glutathione, malondialdehyde, total cholesterol and triglyceride concentrations in hepatic tissues; and blood levels of aspartate aminotransferase, alanine aminotransferase, albumin, gamma-glutaryl transferase, total cholesterol and random glucose. RESULTS: Gingival bleeding index, probing pocket depth, myeloperoxidase and alveolar bone loss parameters demonstrated the development of periodontitis. There was a significant reduction in the steatosis score of animals from the P20-20 group when compared with the periodontitis group. P20-20 group presented significantly higher glutathione (11 times) and lower malondialdehyde (nearly 23%), total cholesterol (both in blood and hepatic tissue) and triglyceride concentrations compared with the periodontitis group. For levels of aspartate aminotransferase, alanine aminotransferase, albumin, gamma-glutaryl transferase and random glucose, a significant difference between the groups was not observed. CONCLUSION: Our results demonstrate that the microvesicular steatosis caused by periodontitis in rats is reversible after removal of the ligature, which is associated with the increase in oxidative stress and lipid peroxidation in the liver.
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Hígado Graso/etiología , Hígado Graso/terapia , Ligadura/métodos , Estrés Oxidativo , Periodontitis/complicaciones , Alanina Transaminasa/sangre , Pérdida de Hueso Alveolar/clasificación , Pérdida de Hueso Alveolar/patología , Animales , Aspartato Aminotransferasas/sangre , Glucemia , Colesterol/análisis , Colesterol/sangre , Modelos Animales de Enfermedad , Hígado Graso/patología , Femenino , Encía/patología , Glutatión/análisis , Inflamación , Peroxidación de Lípido , Hígado/lesiones , Hígado/patología , Malondialdehído/análisis , Necrosis/patología , Índice Periodontal , Bolsa Periodontal/patología , Periodontitis/patología , Peroxidasa/metabolismo , Ratas , Ratas Wistar , Albúmina Sérica , Factores de Tiempo , Transaminasas/sangre , Triglicéridos/análisis , gamma-Glutamiltransferasa/sangreRESUMEN
Evaluating genetic diversity among genotypes is important for providing parameters for the identification of superior genotypes, because the choice of parents that form segregating populations is crucial. Our objectives were to i) evaluate agronomic performance; ii) compare clustering methods; iii) ascertain the relative contributions of the variables evaluated; and iv) identify the most promising hybrids to produce superior segregating populations. The trial was conducted in 2015 at the State University of Mato Grosso do Sul, Brazil. We used a randomized block design with three replications, and recorded the days to emergence, days to flowering, days to maturity, plant height, number of branches, number of pods, number of seeds per pod, weight of 100 grains, and productivity. The genetic diversity of the genotypes was determined by cluster analysis using two dissimilarity measures: the Euclidean distance and the standardized mean Mahalanobis distance using the Ward hierarchical method. The genotypes 'CNFC 10762', 'IAC Dawn', and 'BRS Style' had the highest grain yields, and clusters that were based on the Euclidean distance differed from those based on the Mahalanobis distance, the second being more precise. The yield grain character has greater relevance to the dispute. Hybrids with a high heterotic effect can be obtained by crossing 'IAC Alvorada' with 'CNFC 10762', 'IAC Alvorada' with 'CNFC 10764', and 'BRS Style' with 'IAC Alvorada'.
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Phaseolus/crecimiento & desarrollo , Phaseolus/genética , Agricultura , Brasil , Análisis por Conglomerados , Producción de Cultivos/métodos , Grano Comestible/genética , Grano Comestible/crecimiento & desarrollo , Flujo Genético , Variación Genética/genética , Genotipo , Fenotipo , Semillas/genética , Semillas/crecimiento & desarrolloRESUMEN
Chagas disease is a life-threatening infection caused by a variety of genetically diverse strains of the protozoan parasite Trypanosoma cruzi The current treatment (benznidazole and nifurtimox) is unsatisfactory, and potential alternatives include inhibitors of sterol 14α-demethylase (CYP51), the cytochrome P450 enzyme essential for the biosynthesis of sterols in eukaryotes and the major target of clinical and agricultural antifungals. Here we performed a comparative investigation of two protozoon-specific CYP51 inhibitors, VNI and its CYP51 structure-based derivative VFV, in the murine models of infection caused by the Y strain of T. cruzi The effects of different treatment regimens and drug delivery vehicles were evaluated in animals of both genders, with benznidazole serving as the reference drug. Regardless of the treatment scheme or delivery vehicle, VFV was more potent in both genders, causing a >99.7% peak parasitemia reduction, while the VNI values varied from 91 to 100%. Treatments with VNI and VFV resulted in 100% animal survival and 0% natural relapse after the end of therapy, though, except for the 120-day treatment schemes with VFV, relapses after three cycles of immunosuppression were observed in each animal group, and quantitative PCR analysis revealed a very light parasite load in the blood samples (sometimes below or near the detection limit, which was 1.5 parasite equivalents/ml). Our studies support further investigations of this class of compounds, including their testing against other T. cruzi strains and in combination with other drugs.
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Inhibidores de 14 alfa Desmetilasa/farmacología , Enfermedad de Chagas/tratamiento farmacológico , Sistema Enzimático del Citocromo P-450/química , Imidazoles/farmacología , Oxadiazoles/farmacología , Tripanocidas/farmacología , Trypanosoma cruzi/efectos de los fármacos , Inhibidores de 14 alfa Desmetilasa/química , Animales , Enfermedad de Chagas/inmunología , Enfermedad de Chagas/parasitología , Ciclofosfamida/efectos adversos , Sistema Enzimático del Citocromo P-450/genética , Sistema Enzimático del Citocromo P-450/metabolismo , Modelos Animales de Enfermedad , Esquema de Medicación , Femenino , Expresión Génica , Humanos , Imidazoles/química , Inmunosupresores/efectos adversos , Masculino , Ratones , Modelos Moleculares , Nitroimidazoles/farmacología , Oxadiazoles/química , Carga de Parásitos , Recurrencia , Análisis de Supervivencia , Tripanocidas/química , Trypanosoma cruzi/enzimología , Trypanosoma cruzi/genética , Trypanosoma cruzi/crecimiento & desarrolloRESUMEN
Here we report novel comprehensive investigations on the electronic state spectroscopies of isolated 2,4- and 2,6-difluorotoluene in the gas phase by high-resolution vacuum ultraviolet (VUV) photoabsorption measurements in the 4.4-10.8 eV energy range, with absolute cross-section values derived. We also present the first set of ab initio calculations (vertical energies and oscillator strengths), which we have used in the assignment of valence transitions of the difluorotoluene molecules, together with calculated ionization energies to obtain the Rydberg transitions for both molecules. The measured absolute photoabsorption cross sections have been used to estimate the photolysis lifetimes of 2,4- and 2,6-difluorotoluene in the Earth's atmosphere.
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Arylimidamides (AIAs) have been shown to have considerable biological activity against intracellular pathogens, includingTrypanosoma cruzi, which causes Chagas disease. In the present study, the activities of 12 novel bis-AIAs and 2 mono-AIAs against different strains ofT. cruziin vitroandin vivowere analyzed. The most active wasm-terphenyl bis-AIA (35DAP073), which had a 50% effective concentration (EC50) of 0.5 µM for trypomastigotes (Y strain), which made it 26-fold more effective than benznidazole (Bz; 13 µM). It was also active against the Colombiana strain (EC50= 3.8 µM). Analysis of the activity against intracellular forms of the Tulahuen strain showed that this bis-AIA (EC50= 0.04 µM) was about 100-fold more active than Bz (2 µM). The trypanocidal effect was dissociated from the ability to trigger intracellular lipid bodies within host cells, detected by oil red labeling. Both an active compound (35DAP073) and an inactive compound (26SMB060) displayed similar activation profiles. Due to their high selectivity indexes, two AIAs (35DAP073 and 35DAP081) were moved toin vivostudies, but because of the results of acute toxicity assays, 35DAP081 was excluded from the subsequent tests. The findings obtained with 35DAP073 treatment of infections caused by the Y strain revealed that 2 days of therapy induced a dose-dependent action, leading to 96 to 46% reductions in the level of parasitemia. However, the administration of 10 daily doses in animals infected with the Colombiana strain resulted in toxicity, preventing longer periods of treatment. The activity of the combination of 0.5 mg/kg of body weight/day 35DAP073 with 100 mg/kg/day Bz for 10 consecutive days was then assayed. Treatment with the combination resulted in the suppression of parasitemia, the elimination of neurological toxic effects, and survival of 100% of the animals. Quantitative PCR showed a considerable reduction in the parasite load (60%) compared to that achieved with Bz or the amidine alone. Our results support further investigations of this class with the aim of developing novel alternatives for the treatment of Chagas disease.
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Amidas/farmacología , Enfermedad de Chagas/tratamiento farmacológico , Parasitemia/tratamiento farmacológico , Compuestos de Terfenilo/farmacología , Tripanocidas/farmacología , Trypanosoma cruzi/efectos de los fármacos , Amidas/síntesis química , Amidinas/farmacología , Animales , Enfermedad de Chagas/mortalidad , Enfermedad de Chagas/parasitología , Modelos Animales de Enfermedad , Esquema de Medicación , Cálculo de Dosificación de Drogas , Sinergismo Farmacológico , Quimioterapia Combinada , Femenino , Ratones , Nitroimidazoles/farmacología , Carga de Parásitos , Parasitemia/mortalidad , Parasitemia/parasitología , Pruebas de Sensibilidad Parasitaria , Relación Estructura-Actividad , Análisis de Supervivencia , Compuestos de Terfenilo/síntesis química , Tripanocidas/síntesis química , Trypanosoma cruzi/crecimiento & desarrolloRESUMEN
OBJECTIVE: This study compared the neonatal results of low weight neonates born by cesarean and vaginal delivery. DESIGN: A retrospective cohort study. SETTING: Maternity of Hospital - Irmandade Santa Casa de Misericórdia de São Paulo, Brazil. METHODS: The analysis included the neonates born alive, of unique pregnancy, <2000 g from October 1999 to July 2013. To obtain the information about the neonatal period, as well as their Apgar score in the 1st and 5th min of life, a search in the database of a neonatal intensive care unit was performed. RESULTS: In total, 830 neonates were included as per the study criteria. Of these, 519 (62.5%) were born by cesarean delivery and 311 (37.5%) by vaginal delivery. There was a statistically significant difference in the incidence of neonatal complications, with better results in the neonates born by vaginal delivery, except for the group with neonates <1500 g. In this group, there was a higher incidence of intracranial hemorrhage and death before discharge from the hospital. There was also a higher incidence of respiratory distress syndrome and intraventricular hemorrhage in neonates born by vaginal delivery, in all weight groups. Comparing the Apgar scores, there was a statistically significant difference between the delivery modes, with better results observed in the ones born by vaginal delivery. However, the opposite was observed in the group with neonates <1000 g. CONCLUSION: There was no indication of cesarean delivery benefits in neonates 1000-2000 g. However, the opposite was observed when the neonates were <1000 g.
Asunto(s)
Cesárea , Resultado del Embarazo , Puntaje de Apgar , Brasil , Femenino , Humanos , Recién Nacido de Bajo Peso , Recién Nacido , Recien Nacido Prematuro , Mortalidad Perinatal , Embarazo , Estudios RetrospectivosRESUMEN
According to the International Atomic Energy Agency (IAEA), a relatively significant number of radiological accidents have occurred in recent years mainly because of the practices referred to as potentially high-risk activities, such as radiotherapy, large irradiators and industrial radiography, especially in gammagraphy assays. In some instances, severe injuries have occurred in exposed persons due to high radiation doses. In industrial radiography, 80 cases involving a total of 120 radiation workers, 110 members of the public including 12 deaths have been recorded up to 2014. Radiological accidents in industrial practices in Brazil have mainly resulted in development of cutaneous radiation syndrome (CRS) in hands and fingers. Brazilian data include 5 serious cases related to industrial gammagraphy, affecting 7 radiation workers and 19 members of the public; however, none of them were fatal. Some methods of reconstructive dosimetry have been used to estimate the radiation dose to assist in prescribing medical treatment. The type and development of cutaneous manifestations in the exposed areas of a person is the first achievable gross dose estimation. This review article presents the state-of-the-art reconstructive dosimetry methods enabling estimation of local radiation doses and provides guidelines for medical handling of the exposed individuals. The review also presents the Chilean and Brazilian radiological accident cases to highlight the importance of reconstructive dosimetry.