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1.
Dent Mater ; 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38944559

RESUMO

OBJECTIVE: To assess the influence of calcination process on the properties of minimally processed recycled 3Y-TZP, and to compare it with its commercial counterpart. METHODS: Non-milled 3Y-TZP waste was collected, fragmented and ball-milled to a granulometric < 5 µm. Half of the recycled powder was calcined at 900 °C. Recycled 3Y-TZP disks were uniaxially pressed and sintered to create two recycled groups: 1) Calcined and 2) Non-calcined to be compared with a commercial CAD/CAM milled 3Y-TZP. The microstructure of experimental groups was assessed through density (n = 6), scanning electron microscopy (n = 3) and energy-dispersive X-ray spectroscopy (n = 3); and the crystalline content was evaluated through X-ray diffraction (XRD) (n = 3). Optical and mechanical properties were investigated through reflectance tests (n = 10), and Vickers hardness, fracture toughness (n = 5), and biaxial flexural strength tests (n = 16), respectively. Fractographic analysis was performed to identify fracture origin and crack propagation. Statistical analyses were performed through ANOVA followed by Tukey´s test, and by Weibull statistics. RESULTS: Particle size distribution of recycled powder revealed an average diameter of ∼1.60 µm. The relative density of all experimental groups was > 98.15 % and XRD analysis exhibited a predominance of tetragonal-phase in both recycled groups, which were similar to the crystallographic pattern of the control group. Cross-section micrographs presented flaws on the non-calcined group, and a more homogeneous microstructure for the calcined and commercial groups. Commercial samples showed lower contrast-ratio and higher translucency-parameter than the recycled groups, where non-calcined presented higher translucency-parameter and lower contrast-ratio than its calcined counterpart. The commercial group presented higher fracture toughness and characteristic strength than the recycled groups. Moreover, the calcined group exhibited higher hardness, characteristic strength, and probability of survival at higher loads than the non-calcined group. Fractographic analysis depicted the presence of microstructural flaws in the non-calcined group, which may have acted as stress-raisers and led to failures at lower flexural strengths values. SIGNIFICANCE: The calcination process improved the microstructure, optical, and mechanical properties of the recycled 3Y-TZP.

2.
Nanotechnology ; 35(40)2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-38901412

RESUMO

Hyperpigmentation is a skin disorder characterized by excessive production of melanin in the skin and includes dyschromias such as post-inflammatory hyperchromias, lentigens, melasma and chloasma. Topical products containing depigmenting agents offer a less aggressive treatment option for hyperpigmentation compared to methods like chemical peels and laser sessions. However, some of these agents can cause side effects such as redness and skin irritation. Encapsulating these actives in nanosystems shows promise in mitigating these effects and improving product safety and efficacy. In addition, nanocarriers have the ability to penetrate the skin, potentially allowing for targeted delivery of actives to the affected areas. The most commonly investigated nanosystems are nanoemulsions, vesicular nanosystems and nanoparticles, in which different materials can be used to generate different compositions in order to improve the properties of these nanocarriers. Nanocarriers have already been widely explored, but it is necessary to understand the evolution of these technologies when applied to the treatment of skin hyperchromias. Therefore, this literature review aims to present the state of the art over the last 15 years on the use of nanosystems as a potential strategy for encapsulating depigmenting actives for potential application in cosmetic products for skin hyperchromia. By providing a comprehensive overview of the latest research findings and technological advances, this article can contribute to improving the care and quality of life of people affected by this skin condition.


Assuntos
Portadores de Fármacos , Humanos , Portadores de Fármacos/química , Nanopartículas/química , Hiperpigmentação/tratamento farmacológico , Preparações Clareadoras de Pele/administração & dosagem , Preparações Clareadoras de Pele/química , Pele/efeitos dos fármacos , Pele/metabolismo
3.
Behav Processes ; 219: 105046, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38762054

RESUMO

Delay discounting refers to the decrease in subjective value of a reward as the delay until its receipt increases. In the present study we assessed the effects of the sequence of delay blocks (increasing or decreasing) on discounting and the data systematicity using a titrating procedure with human participants. All participants completed the delay discounting task in both an increasing and decreasing sequence of delays. Delays ranged from one day to ten years. We found steeper discounting when the delays were presented in an increasing sequence compared with when they were presented in a decreasing sequence. We also found steeper discounting when participants completed the increasing sequence condition first. Our results agree with other findings reported in the literature and suggest that delay discounting may be affected by prior and subsequent experience.


Assuntos
Desvalorização pelo Atraso , Recompensa , Humanos , Desvalorização pelo Atraso/fisiologia , Masculino , Feminino , Adulto Jovem , Adulto , Fatores de Tempo
4.
Chemosphere ; 355: 141830, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38552801

RESUMO

Monitoring networks show that the European Union Nitrates Directive (ND) has had mixed success in reducing nitrate concentrations in groundwater. By combining machine learning and monitored nitrate concentrations (1992-2019), we estimate the total area of nitrate hotspots in Europe to be 401,000 km2, with 47% occurring outside of Nitrate Vulnerable Zones (NVZs). We also found contrasting increasing or decreasing trends, varying per country and time periods. We estimate that only 5% of the 122,000 km2 of hotspots in 2019 will meet nitrate quality standards by 2040 and that these may be offset by the appearance of new hotspots. Our results reveal that the effectiveness of the ND is limited by both time-lags between the implementation of good practices and pollution reduction and an inadequate designation of NVZs. Substantial improvements in the designation and regulation of NVZs are necessary, as well as in the quality of monitoring stations in terms of spatial density and information available concerning sampling depth, if the objectives of EU legislation to protect groundwater are to be achieved.


Assuntos
Água Subterrânea , Poluentes Químicos da Água , Nitratos/análise , Monitoramento Ambiental/métodos , Poluentes Químicos da Água/análise , Europa (Continente)
5.
SAR QSAR Environ Res ; 34(12): 983-1001, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38047445

RESUMO

Quantitative structure-activity relationship (QSAR) models are powerful in silico tools for predicting the mutagenicity of unstable compounds, impurities and metabolites that are difficult to examine using the Ames test. Ideally, Ames/QSAR models for regulatory use should demonstrate high sensitivity, low false-negative rate and wide coverage of chemical space. To promote superior model development, the Division of Genetics and Mutagenesis, National Institute of Health Sciences, Japan (DGM/NIHS), conducted the Second Ames/QSAR International Challenge Project (2020-2022) as a successor to the First Project (2014-2017), with 21 teams from 11 countries participating. The DGM/NIHS provided a curated training dataset of approximately 12,000 chemicals and a trial dataset of approximately 1,600 chemicals, and each participating team predicted the Ames mutagenicity of each trial chemical using various Ames/QSAR models. The DGM/NIHS then provided the Ames test results for trial chemicals to assist in model improvement. Although overall model performance on the Second Project was not superior to that on the First, models from the eight teams participating in both projects achieved higher sensitivity than models from teams participating in only the Second Project. Thus, these evaluations have facilitated the development of QSAR models.


Assuntos
Mutagênicos , Relação Quantitativa Estrutura-Atividade , Mutagênicos/toxicidade , Mutagênicos/química , Testes de Mutagenicidade , Mutagênese , Japão
6.
Percept Mot Skills ; 130(2): 680-699, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36745476

RESUMO

The COVID-19 pandemic forced governments to implement measures that disrupted the daily routines of many families worldwide. We studied how the COVID-19 lockdown affected children's routines in Portugal (PT), Brazil (BR), and Italy (IT) to determine if children's age and country impacted their physical activity (PA) and sedentary time. We launched an anonymous online survey to assess how 3-12 years old children adjusted their daily routines to this situation. Parents reported the times each child was engaged in different activities throughout the day, and we used these data to calculate separately overall sedentary and physical activity time. We conducted separate analyses of variance for age and country on the percentage of time spent in the different activities. Results, based on the data from 3045 children in these three countries (PT n = 2044; BR n = 836; IT n = 165), showed that, during lockdown, most children spent most of their awake daily hours in sedentary activities. There was a clear age effect on the way their routines were organized. Percentages of time spent in intellectual activity, playful screen activity, and overall sedentary time were greater in the older age groups, whereas percentages of time spent in play (with and without PA) and in overall PA were greater in the younger groups. We found a main effect of country for all variables except play without PA. The country effect was mainly due to the difference between the routines in BR when compared to PT and IT. Values of playful screen time and overall sedentary activity were higher in BR than in the two European countries. Conversely, values for play with PA, PA, and overall PA (except in the older group) were lower in BR. Patterns of time spent in these activities were similar in IT and PT, but PA and overall PA times were higher in the two younger age groups in IT. In summary, percentage of PA time of confined children was low and decreased with age across all three countries and was particularly low for children in BR relative to those in PT and IT.


Assuntos
COVID-19 , Humanos , Criança , Idoso , Pré-Escolar , COVID-19/epidemiologia , Brasil , Comparação Transcultural , Pandemias , Portugal , Controle de Doenças Transmissíveis , Exercício Físico , Itália/epidemiologia
7.
Braz. j. biol ; 832023.
Artigo em Inglês | LILACS-Express | LILACS, VETINDEX | ID: biblio-1469040

RESUMO

Abstract The species Eugenia involucrata DC. is a plant native to Brazil and is traditionally used for intestinal problems, however, little research has documented about its biological potential and phytochemical profile. Thus, the objective of this study was to carry out preliminary phytochemical prospecting, antimicrobial and antioxidant potential of E. involucrata extracts. Using the E. involucrata leaves, aqueous and organic extracts were obtained using the following solvents (ethanol, methanol, hexane, acetone, dichloromethane and ethyl acetate). The phytochemical prospecting detected the presence of saponins, steroids, flavonoids and tannins in the extracts. Ethanolic and methanolic extracts presented antimicrobial activity for most of the bacterial strains tested, as well as for yeast Candida albicans, with concentrations between 3.12 and 50 mg/mL. The ethanolic and metanolic extract presented high free radical sequestration potential (>90%). The methanol extract showed an IC50 value statistically equal to that found for the commercial antioxidant BHT (p 0.05). The crude extracts obtained with ethanol and methanol were the most promising. These results suggest that methanolic, ethanolic and aqueous extracts are a promising source of natural bioactive.


Resumo A espécie Eugenia involucrata DC. é uma planta nativa do Brasil e tradicionalmente utilizada para problemas intestinais, porém, poucas pesquisas documentam sobre seu potencial biológico e perfil fitoquímico. Assim, o objetivo deste trabalho foi realizar uma prospecção fitoquímica preliminar, o potencial antimicrobiano e antioxidante dos extratos de E. involucrata. A partir das folhas de E. involucrata, foram obtidos extratos aquosos e orgânicos com os seguintes solventes (etanol, metanol, hexano, acetona, diclorometano e acetato de etila). A prospecção fitoquímica detectou a presença de saponinas, esteroides, flavonóides e taninos nos extratos. Os extratos etanólico e metanólico apresentaram atividade antimicrobiana para a maioria das cepas bacterianas testadas, assim como para a levedura Candida albicans, com concentrações entre 3,12 e 50 mg/mL. Os extratos etanólico e metanólico apresentaram alto potencial de sequestro de radicais livres (> 90%). O extrato metanólico apresentou IC50 estatisticamente igual ao encontrado para o antioxidante comercial BHT (p 0,05). Os extratos brutos obtidos com etanol e metanol foram os mais promissores. Esses resultados sugerem que os extratos metanólico, etanólico e aquoso são uma fonte promissora de bioativos naturais.

8.
Braz. j. biol ; 83: e245753, 2023. tab
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1278536

RESUMO

Abstract The species Eugenia involucrata DC. is a plant native to Brazil and is traditionally used for intestinal problems, however, little research has documented about its biological potential and phytochemical profile. Thus, the objective of this study was to carry out preliminary phytochemical prospecting, antimicrobial and antioxidant potential of E. involucrata extracts. Using the E. involucrata leaves, aqueous and organic extracts were obtained using the following solvents (ethanol, methanol, hexane, acetone, dichloromethane and ethyl acetate). The phytochemical prospecting detected the presence of saponins, steroids, flavonoids and tannins in the extracts. Ethanolic and methanolic extracts presented antimicrobial activity for most of the bacterial strains tested, as well as for yeast Candida albicans, with concentrations between 3.12 and 50 mg/mL. The ethanolic and metanolic extract presented high free radical sequestration potential (>90%). The methanol extract showed an IC50 value statistically equal to that found for the commercial antioxidant BHT (p <0.05). The crude extracts obtained with ethanol and methanol were the most promising. These results suggest that methanolic, ethanolic and aqueous extracts are a promising source of natural bioactive.


Resumo A espécie Eugenia involucrata DC. é uma planta nativa do Brasil e tradicionalmente utilizada para problemas intestinais, porém, poucas pesquisas documentam sobre seu potencial biológico e perfil fitoquímico. Assim, o objetivo deste trabalho foi realizar uma prospecção fitoquímica preliminar, o potencial antimicrobiano e antioxidante dos extratos de E. involucrata. A partir das folhas de E. involucrata, foram obtidos extratos aquosos e orgânicos com os seguintes solventes (etanol, metanol, hexano, acetona, diclorometano e acetato de etila). A prospecção fitoquímica detectou a presença de saponinas, esteroides, flavonóides e taninos nos extratos. Os extratos etanólico e metanólico apresentaram atividade antimicrobiana para a maioria das cepas bacterianas testadas, assim como para a levedura Candida albicans, com concentrações entre 3,12 e 50 mg/mL. Os extratos etanólico e metanólico apresentaram alto potencial de sequestro de radicais livres (> 90%). O extrato metanólico apresentou IC50 estatisticamente igual ao encontrado para o antioxidante comercial BHT (p <0,05). Os extratos brutos obtidos com etanol e metanol foram os mais promissores. Esses resultados sugerem que os extratos metanólico, etanólico e aquoso são uma fonte promissora de bioativos naturais.


Assuntos
Eugenia , Anti-Infecciosos/farmacologia , Brasil , Extratos Vegetais/farmacologia , Folhas de Planta , Compostos Fitoquímicos , Antioxidantes/farmacologia
9.
Sci Rep ; 12(1): 11260, 2022 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-35789175

RESUMO

Muscle diseases share common pathological features suggesting common underlying mechanisms. We hypothesized there is a common set of genes dysregulated across muscle diseases compared to healthy muscle and that these genes correlate with severity of muscle disease. We performed meta-analysis of transcriptional profiles of muscle biopsies from human muscle diseases and healthy controls. Studies obtained from public microarray repositories fulfilling quality criteria were divided into six categories: (i) immobility, (ii) inflammatory myopathies, (iii) intensive care unit (ICU) acquired weakness (ICUAW), (iv) congenital muscle diseases, (v) chronic systemic diseases, (vi) motor neuron disease. Patient cohorts were separated in discovery and validation cohorts retaining roughly equal proportions of samples for the disease categories. To remove bias towards a specific muscle disease category we repeated the meta-analysis five times by removing data sets corresponding to one muscle disease class at a time in a "leave-one-disease-out" analysis. We used 636 muscle tissue samples from 30 independent cohorts to identify a 52 gene signature (36 up-regulated and 16 down-regulated genes). We validated the discriminatory power of this signature in 657 muscle biopsies from 12 additional patient cohorts encompassing five categories of muscle diseases with an area under the receiver operating characteristic curve of 0.91, 83% sensitivity, and 85.3% specificity. The expression score of the gene signature inversely correlated with quadriceps muscle mass (r = -0.50, p-value = 0.011) in ICUAW and shoulder abduction strength (r = -0.77, p-value = 0.014) in amyotrophic lateral sclerosis (ALS). The signature also positively correlated with histologic assessment of muscle atrophy in ALS (r = 0.88, p-value = 1.62 × 10-3) and fibrosis in muscular dystrophy (Jonckheere trend test p-value = 4.45 × 10-9). Our results identify a conserved transcriptional signature associated with clinical and histologic muscle disease severity. Several genes in this conserved signature have not been previously associated with muscle disease severity.


Assuntos
Esclerose Lateral Amiotrófica , Doenças Musculares , Esclerose Lateral Amiotrófica/genética , Estudos de Coortes , Humanos , Doenças Musculares/genética , Músculo Quadríceps , Índice de Gravidade de Doença
10.
Percept Mot Skills ; 129(5): 1362-1380, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35790415

RESUMO

Harmonious voluntary movements require efficiency in their planning and execution. Throughout middle childhood structural changes in the central nervous and musculoskeletal systems influence these processes and resultant motor behavior. In this study, we evaluated the characteristics of the motor planning and executing of aiming movements directed at targets located in different positions in space in children aged 7, 9, and 11 years. We divided 43 right-handed children, into three age groups and instructed them to perform aiming movements directed at targets using a stylus on a digital tablet. The children performed the movement with their dominant upper limbs from a starting point towards targets positioned ipsilaterally or contralaterally to this dominant limb. We analyzed temporal and spatial variables of motor performance. Younger (7-year-old) children made more errors in the initial movement direction and more frequently corrected their movements during task execution when compared to 9- and 11-year-old children who did not differ from each other. All age groups were similar in movement accuracy and precision. Movements toward contralateral targets were slower and more accurate than movements toward ipsilateral targets for all groups. These results show that performing aiming movements develop with the onset of middle childhood.


Assuntos
Lateralidade Funcional , Desempenho Psicomotor , Criança , Lateralidade Funcional/fisiologia , Mãos/fisiologia , Humanos , Movimento/fisiologia , Desempenho Psicomotor/fisiologia , Extremidade Superior
11.
Braz J Biol ; 84: e259131, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35674597

RESUMO

Scolytinae species that, in high populations, can damage reducing wood production in forest crops. These beetles are monitored with traps baited with ethanol and increasing their efficiency can improve the integrated management of these insects. The objective was to evaluate the increase in the capture efficiency of Scolytinae with a semi-funnel trap model, in two experiments, one including wooden elements and other increasing the flight interception area and to correlate the numbers of these beetles collected with climatic factors. In the experiment 1, Eucalyptus urophylla S. T. Blake slats were directly attached to the collector flask and in another treatment, in addition to these slats, Cedrela sp. strips were inserted inside the bait holding hose. In the experiment 2, the insect interception area in the trap, originally 480 cm2, was expanded to 1,200 cm2 and compared with the model Pet-Santa Maria trap with an interception area of 550 cm2. Weekly collections were carried out between May 2018 and June 2019. The beetles collected were taken to the Wood Biodeterioration Laboratory of the Federal Rural University of Rio de Janeiro (UFRRJ) where they were sorted, identified at family level, counted and their number correlated with climatic factors. Statistical analyzes of the collected data were processed by the BioStat® 5.3 program. In the experiment 1 were collected 869 Scolytinae. The numbers of beetles collected per trap without modification, with E. urophylla slats and E. urophylla slats + Cedrela sp. strips were similar, 7.3 ± 3.8, 7.8 ± 6.2 and 7.7 ± 5.0 respectively. In the experiment 2 were collected 4,398 Scolytinae. Increasing the interception area of the beetles increased the efficiency of the semi-funnel trap, with 42.7 ± 20.5 Scolytinae collected compared to the original semi-funnel trap, 28.6 ± 12.6 and the Pet-Santa Maria, 20.4 ± 10.4, per trap. The number of Scolytinae did not correlate with climatic factors in the experiment 1 and it was correlated with temperature, relative humidity and wind speed, but not with precipitation, in the 2. The incorporation of E. urophylla slats or Cedrela sp. strips in the semi-funnel trap did not increase the number of beetles collected, but, the increase in the flight interception area and the temperature, relative humidity and wind speed were correlated with the number of beetles collected.


Assuntos
Besouros , Eucalyptus , Gorgulhos , Animais , Controle de Insetos , Temperatura
12.
J Econ Entomol ; 115(3): 706-714, 2022 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-35526117

RESUMO

Beekeeping contributes to poverty reduction in many developing countries, and in addition, provides pollination services for sustainable crop production. In Nepal, management practices associated with beekeeping are poorly characterized, and so the potential for this sector to further contribute to livelihood development remains unclear. This study sought to examine and identify factors associated with production efficiency and financial profitability of beekeeping with the aim of enhancing economic gains for Nepali beekeepers. Our study included a sample of 150 respondents from more than twenty commercial beekeeping districts across the Terai and mountainous regions of Nepal. Profitability of beekeeping with the European honeybee (Apis mellifera) Linnaeus, 1758 (Hymenoptera: Apidae) and the Asian honeybee Apis cerana Fabricius, 1793 (Hymenoptera: Apidae) was quantified and disaggregated according to several variables, including hive-derived products produced, marketing strategy employed, number of beehives managed, and postharvest management practices. Our results showed that the different types of management practices adopted (such as number of beehives kept, colony multiplication, supplementary feeding, month of honey harvesting, and marketing approach) significantly influenced the productivity and economic profitability of beekeeping. Our results also revealed that professional supports, such as the availability of subsidies and training, were key factors to enhance productivity. As a whole, this study provides insight into the biological factors and management practices associated with higher economic returns from beekeeping. This work can help guide policymakers and professional support agencies to expand commercial beekeeping for sustainable livelihood development in Nepal and beyond.


Assuntos
Criação de Abelhas , Mel , Animais , Abelhas , Humanos , Nepal , Polinização
13.
Forensic Sci Int ; 335: 111281, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35429777

RESUMO

We discuss how different accelerator-based techniques can be employed synergistically as a powerful analytical tool for forensic studies of foodstuff. Brazilian and Jamaican coffees were chosen as a showcase due to its popularity and potential risk of adulteration and/or falsification. Comprehensive characterization of major and trace elements, age since production and compound contents were achieved using different techniques, including PIXE (Particle-Induced X-ray Emission), FTIR (Fourier Transform Infrared), and AMS-14C (Accelerator Mass Spectrometry - Radiocarbon Analysis). While PIXE provides information on the elements present in the samples, FTIR probes the types of compounds through their vibrational spectra. Finally, AMS-14C is capable of dating organic samples regarding their harvesting time. Five different laboratories from research institutions around the world took part in the experiments. The integration of the results obtained with different techniques provided multifaceted perspectives on the coffee under study, thus allowing a direct assessment of the material for forensic purposes such as authentication, determination of provenance, and combat counterfeiting.


Assuntos
Café , Oligoelementos , Brasil , Contaminação de Medicamentos , Espectrometria de Massas/métodos
14.
Drug Chem Toxicol ; 45(5): 2003-2013, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33685320

RESUMO

The diminazene aceturate (C14H15N7.2C4H7NO3) is a chemotherapeutic agent with more than six decades of use, however more studies regarding its toxicity still need to be performed. Thus, the present study determined the acute toxicity (14 days) of diminazene acetate (DIZE) in male and female swiss mice by changes in body mass, food consumption, biochemical and hematological parameters, locomotor activity and motor coordination. DIZE was administered at a single dose (1000 and 2000 mg/kg) orally. In addition, in vitro antioxidant capacity, hemolytic activity, toxicity in Artemia salina and in silico evaluation were also performed. The results obtained include several signs of toxicity (hypoactivity, loss of the straightening reflex and tachycardia), reduction of behavioral activity (locomotor activity and motor coordination) and significant changes (p < 0.05) in biochemical and hematological parameters. According to the in silico study, the DIZE can be classified based on the mean lethal dose (LD50) in category 4 (300 mg/kg < LD50 ≤ 2000 mg/kg, ProTox-II) or 3 (50 mg/kg < LD50 ≤ 300 mg/kg, AdmetSAR 1.0). Additionally, DIZE (30.3-969.9 nM) was not toxic to A. salina in the first 48 hours of treatment and was not cytotoxic to rat red blood cells after induced hemolysis. In vitro results indicated low antioxidant capacity against DPPH• and ABTS•+ radicals. Therefore, DIZE induces several adverse effects with influence on the central nervous system, changes in hematological and biochemical parameters and even mortality at the highest dose. However, absence of toxicity was observed in A. salina and rats red blood cells.


Assuntos
Antiparasitários , Diminazena , Enzima de Conversão de Angiotensina 2 , Animais , Antioxidantes , Antiparasitários/uso terapêutico , Diminazena/análogos & derivados , Diminazena/toxicidade , Feminino , Masculino , Camundongos , Peptidil Dipeptidase A , Ratos , Ratos Wistar
15.
Intensive Care Med Exp ; 9(1): 61, 2021 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-34970706

RESUMO

Severe viral pneumonia is a significant cause of morbidity and mortality globally, whether due to outbreaks of endemic viruses, periodic viral epidemics, or the rarer but devastating global viral pandemics. While limited anti-viral therapies exist, there is a paucity of direct therapies to directly attenuate viral pneumonia-induced lung injury, and management therefore remains largely supportive. Mesenchymal stromal/stem cells (MSCs) are receiving considerable attention as a cytotherapeutic for viral pneumonia. Several properties of MSCs position them as a promising therapeutic strategy for viral pneumonia-induced lung injury as demonstrated in pre-clinical studies in relevant models. More recently, early phase clinical studies have demonstrated a reassuring safety profile of these cells. These investigations have taken on an added importance and urgency during the COVID-19 pandemic, with multiple trials in progress across the globe. In parallel with clinical translation, strategies are being investigated to enhance the therapeutic potential of these cells in vivo, with different MSC tissue sources, specific cellular products including cell-free options, and strategies to 'licence' or 'pre-activate' these cells, all being explored. This review will assess the therapeutic potential of MSC-based therapies for severe viral pneumonia. It will describe the aetiology and epidemiology of severe viral pneumonia, describe current therapeutic approaches, and examine the data suggesting therapeutic potential of MSCs for severe viral pneumonia in pre-clinical and clinical studies. The challenges and opportunities for MSC-based therapies will then be considered.

16.
Sci Rep ; 11(1): 19634, 2021 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-34608194

RESUMO

The persistent increase of multidrug-resistant (MDR) Mycobacterium tuberculosis (Mtb) infections negatively impacts Tuberculosis treatment outcomes. Host-directed therapies (HDT) pose an complementing strategy, particularly since Mtb is highly successful in evading host-defense by manipulating host-signaling pathways. Here, we screened a library containing autophagy-modulating compounds for their ability to inhibit intracellular Mtb-bacteria. Several active compounds were identified, including two drugs of the diphenylbutylpiperidine-class, Fluspirilene and Pimozide, commonly used as antipsychotics. Both molecules inhibited intracellular Mtb in pro- as well as anti-inflammatory primary human macrophages in a host-directed manner and synergized with conventional anti-bacterials. Importantly, these inhibitory effects extended to MDR-Mtb strains and the unrelated intracellular pathogen, Salmonella enterica serovar Typhimurium (Stm). Mechanistically Fluspirilene and Pimozide were shown to regulate autophagy and alter the lysosomal response, partly correlating with increased bacterial localization to autophago(lyso)somes. Pimozide's and Fluspirilene's efficacy was inhibited by antioxidants, suggesting involvement of the oxidative-stress response in Mtb growth control. Furthermore, Fluspirilene and especially Pimozide counteracted Mtb-induced STAT5 phosphorylation, thereby reducing Mtb phagosome-localized CISH that promotes phagosomal acidification. In conclusion, two approved antipsychotic drugs, Pimozide and Fluspirilene, constitute highly promising and rapidly translatable candidates for HDT against Mtb and Stm and act by modulating the autophagic/lysosomal response by multiple mechanisms.


Assuntos
Antibacterianos/farmacologia , Antipsicóticos/farmacologia , Antituberculosos/farmacologia , Reposicionamento de Medicamentos , Mycobacterium tuberculosis/efeitos dos fármacos , Salmonella enterica/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Linhagem Celular , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Ensaios de Triagem em Larga Escala , Humanos , Lisossomos/metabolismo , Testes de Sensibilidade Microbiana , Modelos Biológicos , Fagossomos/metabolismo , Pimozida/farmacologia , Infecções por Salmonella/tratamento farmacológico , Infecções por Salmonella/microbiologia , Bibliotecas de Moléculas Pequenas , Tuberculose/tratamento farmacológico , Tuberculose/microbiologia
17.
Braz J Biol ; 83: e245753, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34190760

RESUMO

The species Eugenia involucrata DC. is a plant native to Brazil and is traditionally used for intestinal problems, however, little research has documented about its biological potential and phytochemical profile. Thus, the objective of this study was to carry out preliminary phytochemical prospecting, antimicrobial and antioxidant potential of E. involucrata extracts. Using the E. involucrata leaves, aqueous and organic extracts were obtained using the following solvents (ethanol, methanol, hexane, acetone, dichloromethane and ethyl acetate). The phytochemical prospecting detected the presence of saponins, steroids, flavonoids and tannins in the extracts. Ethanolic and methanolic extracts presented antimicrobial activity for most of the bacterial strains tested, as well as for yeast Candida albicans, with concentrations between 3.12 and 50 mg/mL. The ethanolic and metanolic extract presented high free radical sequestration potential (>90%). The methanol extract showed an IC50 value statistically equal to that found for the commercial antioxidant BHT (p <0.05). The crude extracts obtained with ethanol and methanol were the most promising. These results suggest that methanolic, ethanolic and aqueous extracts are a promising source of natural bioactive.


Assuntos
Anti-Infecciosos , Eugenia , Anti-Infecciosos/farmacologia , Antioxidantes/farmacologia , Brasil , Compostos Fitoquímicos , Extratos Vegetais/farmacologia , Folhas de Planta
18.
Int J Oral Maxillofac Surg ; 50(9): 1259-1266, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33632576

RESUMO

This study was performed to evaluate the short-term preservation of alveolar bone volume with or without a polypropylene barrier and exposure of the area after extractions. Thirty posterior tooth extraction sockets were distributed randomly to a control group (n=15; extraction and suture) and a barrier group (n=15; extraction, barrier, and suture). All sutures and barriers were removed 10 days postoperatively. Cone beam computed tomography scans taken with the aid of a tomographic guide were obtained preoperatively, immediately postoperative, and at 120 days postoperative. A visual analysis of the coronal sections of the alveolus was performed, and vertical loss in the mesial, distal, buccal, and lingual bone ridges and horizontal thickness were evaluated. The mean vertical loss after extraction did not differ significantly between the control and barrier groups (Student t-test: mesial P= 0.989, buccal P= 0.997, lingual/palatal P= 0.070, distal P= 0.107). The mean vertical loss at 120 days postoperative did not differ significantly between the control (0.65 mm) and barrier (0.52 mm) groups (P> 0.05), with an effect size of 0.13 mm. At 120 days, the barrier group presented a mean resorption in thickness (0.45 mm) that was significantly lower than that in the control group (0.76 mm) (P= 0.021), with an effect size of 0.31 mm. The polypropylene barrier reduced the horizontal resorption in sockets of posterior teeth after extraction.


Assuntos
Perda do Osso Alveolar , Aumento do Rebordo Alveolar , Perda do Osso Alveolar/diagnóstico por imagem , Perda do Osso Alveolar/prevenção & controle , Tomografia Computadorizada de Feixe Cônico , Humanos , Polipropilenos , Extração Dentária , Alvéolo Dental/diagnóstico por imagem , Alvéolo Dental/cirurgia
19.
Curr Mol Pharmacol ; 14(1): 36-51, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32386503

RESUMO

BACKGROUND: Central nervous system disorders such as anxiety, depression and epilepsy are characterized by sharing several molecular mechanisms in common and the involvement of the L-arginine/NO pathway in neurobehavioral studies with ß-caryophyllene is still little discussed. OBJECTIVES: One of the objectives of the present study was to demonstrate the anxiolytic behavioral effect of ß-caryophyllene (ß-CBP) in female Swiss mice, as well as to investigate the molecular mechanisms underlying the results obtained. METHODS: This study evaluated the neurobehavioral effects of ß-CBP using the open field test, rota- rod test, elevated plus maze test, novelty suppressed feeding test, tail suspension test and forced swim test, as well as pilocarpine, pentylenetetrazole and isoniazid-induced epileptic seizure models. RESULTS: The results demonstrated that the neuropharmacological activities of ß-CBP may involve benzodiazepine/GABAergic receptors, since the pre-treatment of ß-CBP (200 mg/kg) associated with flumazenil (5 mg/kg, benzodiazepine receptor antagonist) and bicuculline (1 mg/kg, selective GABAA receptor antagonist) reestablished the anxiety parameters in the elevated plus-maze test, as well as the results of reduced latency to consume food in the novelty suppressed feeding test. In addition to benzodiazepine/GABAergic receptors, the neuropharmacological properties of ß-CBP may be related to inhibition of nitric oxide synthesis, since pre-treatment with L-arginine (500-750 mg/kg) reversed significantly the anxiolytic, antidepressant and anticonvulsant activities of ß-CBP. CONCLUSION: The results obtained provide additional support in understanding the neuromolecular mechanisms underlying the anxiolytic, antidepressant and anticonvulsive properties of ß-CBP in female Swiss mice.


Assuntos
Ansiolíticos/química , Anticonvulsivantes/química , Antidepressivos/química , Antagonistas de Receptores de GABA-A/química , Sesquiterpenos Policíclicos/química , Animais , Ansiolíticos/farmacologia , Anticonvulsivantes/farmacologia , Antidepressivos/farmacologia , Arginina , Comportamento Animal , Benzodiazepinas/metabolismo , Bicuculina/química , Bicuculina/farmacologia , Feminino , Flumazenil/química , Flumazenil/farmacologia , Antagonistas de Receptores de GABA-A/farmacologia , Humanos , Aprendizagem em Labirinto , Camundongos , Óxido Nítrico/metabolismo , Sesquiterpenos Policíclicos/farmacologia , Receptores de GABA-A/metabolismo , Convulsões/induzido quimicamente , Transdução de Sinais
20.
Sci Rep ; 10(1): 16379, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33009433

RESUMO

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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