Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 18.050
Filtrar
1.
Pestic Biochem Physiol ; 168: 104617, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32711778

RESUMO

The projection of plant protection products' (PPPs) toxicity to non-target organisms at early stages of their development is challenging and demanding. Recent developments in bioanalytics, however, have facilitated the study of fluctuations in the metabolism of biological systems in response to treatments with bioactives and the discovery of corresponding toxicity biomarkers. Neonicotinoids are improved insecticides that target nicotinic acetylocholine receptors (nAChR) in insects which are similar to mammals. Nonetheless, they have sparked controversy due to effects on non-target organisms. Within this context, mammalian cell cultures represent ideal systems for the development of robust models for the dissection of PPPs' toxicity. Thus, we have investigated the toxicity of imidacloprid, clothianidin, and their mixture on primary mouse (Mus musculus) neural stem/progenitor (NSPCs) and mouse neuroblastoma-derived Neuro-2a (N2a) cells, and the undergoing metabolic changes applying metabolomics. Results revealed that NSPCs, which in vitro resemble those that reside in the postnatal and adult central nervous system, are five to seven-fold more sensitive than N2a to the applied insecticides. The energy equilibrium of NSPCs was substantially altered, as it is indicated by fluctuations of metabolites involved in energy production (e.g. glucose, lactate), Krebs cycle intermediates, and fatty acids, which are important components of cell membranes. Such evidence plausibly suggests a switch of cells' energy-producing mechanism to the direct metabolism of glucose to lactate in response to insecticides. The developed pipeline could be further exploited in the discovery of unintended effects of PPPs at early steps of development and for regulatory purposes.


Assuntos
Inseticidas , Nitrocompostos , Animais , Guanidinas , Homeostase , Metabolômica , Camundongos , Neonicotinoides , Sistema Nervoso , Células-Tronco , Tiazóis
3.
BMC Infect Dis ; 20(1): 478, 2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32631240

RESUMO

BACKGROUND: Extended use of oseltamivir in an immunocompromised host could reportedly induce neuraminidase gene mutation possibly leading to oseltamivir-resistant influenza A/H3N2 virus. To our knowledge, no report is available on the clinical course of a severely immunocompromised patient with a dual E119D/R292K neuraminidase mutated-influenza A/H3N2 during the administration of peramivir. CASE PRESENTATION: A 49-year-old male patient was admitted for second allogeneic hematopoietic cell transplantation for active acute leukemia. The patient received 5 mg prednisolone and 75 mg cyclosporine and had severe lymphopenia (70/µL). At the time of hospitalization, the patient was diagnosed with upper tract influenza A virus infection, and oseltamivir treatment was initiated immediately. However, the patient was intolerant to oseltamivir. The following day, treatment was changed to peramivir. Despite a total period of neuraminidase-inhibitor administration of 16 days, the symptoms and viral shedding continued. Changing to baloxavir marboxil resolved the symptoms, and the influenza diagnostic test became negative. Subsequently, sequence analysis of the nasopharyngeal specimen revealed the dual E119D/R292K neuraminidase mutant influenza A/H3N2. CONCLUSIONS: In a highly immunocompromised host, clinicians should take care when peramivir is used for extended periods to treat influenza virus A/H3N2 infection as this could potentially leading to a dual E119D/R292K substitution in neuraminidase protein. Baloxavir marboxil may be one of the agents that can be used to treat this type of mutated influenza virus infection.


Assuntos
Antivirais/uso terapêutico , Ciclopentanos/uso terapêutico , Farmacorresistência Viral/efeitos dos fármacos , Inibidores Enzimáticos/uso terapêutico , Guanidinas/uso terapêutico , Vírus da Influenza A Subtipo H3N2/genética , Influenza Humana/tratamento farmacológico , Oxazinas/uso terapêutico , Piridinas/uso terapêutico , Tiepinas/uso terapêutico , Triazinas/uso terapêutico , Ciclopentanos/efeitos adversos , Ciclopentanos/farmacologia , Farmacorresistência Viral/genética , Inibidores Enzimáticos/efeitos adversos , Inibidores Enzimáticos/farmacologia , Guanidinas/efeitos adversos , Guanidinas/farmacologia , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Hospedeiro Imunocomprometido , Influenza Humana/virologia , Masculino , Pessoa de Meia-Idade , Mutação , Neuraminidase/antagonistas & inibidores , Neuraminidase/genética , Oseltamivir/uso terapêutico , Transplante Homólogo/métodos , Resultado do Tratamento , Proteínas Virais/antagonistas & inibidores , Proteínas Virais/genética
4.
Viruses ; 12(6)2020 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-32532094

RESUMO

Although infection by SARS-CoV-2, the causative agent of coronavirus pneumonia disease (COVID-19), is spreading rapidly worldwide, no drug has been shown to be sufficiently effective for treating COVID-19. We previously found that nafamostat mesylate, an existing drug used for disseminated intravascular coagulation (DIC), effectively blocked Middle East respiratory syndrome coronavirus (MERS-CoV) S protein-mediated cell fusion by targeting transmembrane serine protease 2 (TMPRSS2), and inhibited MERS-CoV infection of human lung epithelium-derived Calu-3 cells. Here we established a quantitative fusion assay dependent on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S protein, angiotensin I converting enzyme 2 (ACE2) and TMPRSS2, and found that nafamostat mesylate potently inhibited the fusion while camostat mesylate was about 10-fold less active. Furthermore, nafamostat mesylate blocked SARS-CoV-2 infection of Calu-3 cells with an effective concentration (EC)50 around 10 nM, which is below its average blood concentration after intravenous administration through continuous infusion. On the other hand, a significantly higher dose (EC50 around 30 mM) was required for VeroE6/TMPRSS2 cells, where the TMPRSS2-independent but cathepsin-dependent endosomal infection pathway likely predominates. Together, our study shows that nafamostat mesylate potently inhibits SARS-CoV-2 S protein-mediated fusion in a cell fusion assay system and also inhibits SARS-CoV-2 infection in vitro in a cell-type-dependent manner. These findings, together with accumulated clinical data regarding nafamostat's safety, make it a likely candidate drug to treat COVID-19.


Assuntos
Anticoagulantes/farmacologia , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Guanidinas/farmacologia , Pneumonia Viral/tratamento farmacológico , Glicoproteína da Espícula de Coronavírus/antagonistas & inibidores , Internalização do Vírus/efeitos dos fármacos , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Betacoronavirus/metabolismo , Linhagem Celular , Chlorocebus aethiops , Infecções por Coronavirus/virologia , Gabexato/análogos & derivados , Gabexato/farmacologia , Células HEK293 , Humanos , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/virologia , Serina Endopeptidases/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo , Células Vero
5.
Viruses ; 12(6)2020 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-32517266

RESUMO

In late 2019, a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, the capital of the Chinese province Hubei. Since then, SARS-CoV-2 has been responsible for a worldwide pandemic resulting in over 4 million infections and over 250,000 deaths. The pandemic has instigated widespread research related to SARS-CoV-2 and the disease that it causes, COVID-19. Research into this new virus will be facilitated by the availability of clearly described and effective procedures that enable the propagation and quantification of infectious virus. As work with the virus is recommended to be performed at biosafety level 3, validated methods to effectively inactivate the virus to enable the safe study of RNA, DNA, and protein from infected cells are also needed. Here, we report methods used to grow SARS-CoV-2 in multiple cell lines and to measure virus infectivity by plaque assay using either agarose or microcrystalline cellulose as an overlay as well as a SARS-CoV-2 specific focus forming assay. We also demonstrate effective inactivation by TRIzol, 10% neutral buffered formalin, beta propiolactone, and heat.


Assuntos
Betacoronavirus/fisiologia , Infecções por Coronavirus/virologia , Pneumonia Viral/virologia , Ensaio de Placa Viral/métodos , Inativação de Vírus , Animais , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/crescimento & desenvolvimento , Betacoronavirus/patogenicidade , Celulose , Chlorocebus aethiops , Meios de Cultura/química , Formaldeído , Guanidinas/farmacologia , Células HEK293 , Humanos , Pandemias , Fenóis/farmacologia , Propiolactona/farmacologia , Sefarose , Células Vero
6.
Pestic Biochem Physiol ; 167: 104601, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32527429

RESUMO

Dinotefuran, the third-generation neonicotinoid, has been applied against melon/cotton aphid Aphis gossypii Glover in China. The risk of resistance development, cross-resistance pattern and potential resistance mechanism of dinotefuran in A. gossypii were investigated. A dinotefuran-resistant strain of A. gossypii (DinR) with 74.7-fold resistance was established by continuous selection using dinotefuran. The DinR strain showed a medium level of cross resistance to thiamethoxam (15.2-fold), but no cross resistance to imidacloprid. The synergism assay indicated that piperonyl butoxide and triphenyl phosphate showed synergistic effects on dinotefuran toxicity to the DinR strain with a synergistic ratio of 8.3 and 2.5, respectively, while diethyl maleate showed no synergistic effect. The activities of cytochrome P450 monooxygenase and carboxylesterase were significantly higher in DinR strain than in susceptible strain (SS). Moreover, the gene expression results showed that CYP6CY14, CYP6CY22 and CYP6UN1 were significantly overexpressed in DinR strain compared with SS strain. The expression of CYP6CY14 was 5.8-fold higher in DinR strain than in SS strain. Additionally, the transcription of CYP6CY14, CYP6CY22 and CYP6UN1 in A. gossypii showed dose- and time-dependent responses to dinotefuran exposure. Furthermore, knockdown of CYP6CY14, CYP6CY22 and CYP6UN1 via RNA interference (RNAi) significantly increased mortality of A. gossypii, when A. gossypii was treated with dinotefuran. These results demonstrated the overexpression of CYP6CY14, CYP6CY22 and CYP6UN1 contributed to dinotefuran resistance in A. gossypii.


Assuntos
Afídeos , Cucurbitaceae , Inseticidas , Animais , China , Sistema Enzimático do Citocromo P-450 , Guanidinas , Resistência a Inseticidas , Neonicotinoides , Nitrocompostos
7.
Ann Lab Med ; 40(6): 439-447, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32539299

RESUMO

Coronavirus disease 2019 (COVID-19) is a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Early detection of COVID-19 and immediate isolation of infected patients from the naive population are important to prevent further pandemic spread of the infection. Real-time reverse transcription (RT)-PCR to detect SARS-CoV-2 RNA is currently the most reliable diagnostic method for confirming COVID-19 worldwide. Guidelines for clinical laboratories on the COVID-19 diagnosis have been recently published by Korean Society for Laboratory Medicine and the Korea Centers for Disease Control and Prevention. However, these formal guidelines do not address common practical laboratory issues related to COVID-19 real-time RT-PCR testing and their solutions. Therefore, this guideline is intended as a practical and technical supplement to the "Guidelines for Laboratory Diagnosis of COVID-19 in Korea".


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Infecções por Coronavirus/genética , Infecções por Coronavirus/virologia , Guanidinas/química , Guias como Assunto , Humanos , Nasofaringe/virologia , Proteínas do Nucleocapsídeo/genética , Fases de Leitura Aberta/genética , Orofaringe/virologia , Pandemias , Pneumonia Viral/genética , Pneumonia Viral/virologia , RNA Viral/genética , RNA Viral/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , República da Coreia , Tiocianatos/química , Proteínas do Envelope Viral/genética
8.
Arch Environ Contam Toxicol ; 79(1): 12-22, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32447405

RESUMO

This study measured both nutrient and pesticide concentrations at up to 13 different freshwater stream sites in New Brunswick, Nova Scotia and Prince Edward Island between 2013 and 2018. Up to 62 different pesticides were analysed in 248 discreet samples. A large majority of pesticides were below the detection limit of the laboratory while seven pesticides had at least 20% or more detections throughout the years of this study. The four pesticides that had the highest frequency of detection were the insecticides chlorantraniliprole, clothianidin, imidacloprid, and thiamethoxam of which the last three are categorised as neonicotinoid insecticides.


Assuntos
Monitoramento Ambiental/métodos , Praguicidas/análise , Rios/química , Poluentes Químicos da Água/análise , Canadá , Guanidinas/análise , Neonicotinoides/análise , Nitrocompostos/análise , Análise Espaço-Temporal , Tiametoxam/análise , Tiazóis/análise
9.
Environ Sci Pollut Res Int ; 27(23): 29599-29611, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32445149

RESUMO

Clothianidin served as the model pollutant to investigate the performance and mechanism of pollutant removal by dielectric barrier discharge plasma (DBD) combined with the titanium dioxide-reduced graphene oxide (rGO-TiO2) composite catalyst. In this study, different ratios of titanium dioxide-graphene catalysts were loaded onto honeycomb ceramic plates via the sol-gel method, and the modified catalytic ceramic plates were characterized by XRD, SEM, FTIR, DRS, and energy dispersive X-ray. The results suggested that the rGO-TiO2 was well loaded on the surface of the honeycomb ceramic plates. According to the results of the characterization experiments and the degradation of the clothianidin solution with different proportions of the catalyst, 8 wt% rGO-TiO2 was selected as the optimum ratio for degradation. Clothianidin degradation efficiency was significantly influenced by input power, clothianidin concentration, pH value, liquid conductivity, free radical quencher. Finally, six degradation products of clothianidin were identified by HPLC-MS, and the possible transformation pathways of clothianidin degradation were identified. Graphical abstract.


Assuntos
Grafite , Catálise , Guanidinas , Neonicotinoides , Tiazóis , Titânio
10.
Environ Sci Pollut Res Int ; 27(24): 30405-30418, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32458307

RESUMO

Composting is an emerging strategy for swine slurry treatment; nonetheless, significant greenhouse gases (GHG) emissions may occur during this process. We carried out two separate assays with increasing doses of dicyandiamide (DCD; up to 1.1% w/w) as a nitrification inhibitor and solutions of MgCl2 and H3PO4 (Mg/P; up to 0.09/0.06 mol kg-1) to promote struvite crystallization in order to assess their efficiencies as additives to decrease GHG emission during swine slurry cocomposting with sawdust (1:1v/v). We monitored the nitrous oxide (N2O-N), methane (CH4-C), and carbon dioxide (CO2-C) emissions and the ammonia (NH4+-N) and nitrate/nitrite (NOx-N) concentrations in compost reactors (35 L) during the first 4-5 weeks of composting. DCD had no effect on CH4-C and CO2-C emissions but decreased N2O-N losses by up to 56% compared with control. However, DCD inactivation was favored by thermophilic conditions and N2O-N emissions increased to same levels of control after 13 days. Mg/P was effective to decrease N2O-N losses only at the highest dose, which also sustained higher [NH4+-N] in the compost by the end of the assessment. Nonetheless, the use of 0.09/0.06 mol kg-1 of Mg/P also decreased CH4-C and CO2-C emissions compared with lower doses of Mg/P and unamended treatments. Overall, DCD and Mg/P amendments decreased the global warming potential (GWP) of swine slurry composting by up to 46 and 28%, respectively. The Mg/P application may be also interesting to increase the compost quality by increasing its NH4+-N availability. Graphical abstract.


Assuntos
Aquecimento Global , Gases de Efeito Estufa , Animais , Dióxido de Carbono/análise , Guanidinas , Metano/análise , Óxido Nitroso/análise , Solo , Suínos
11.
Int J Infect Dis ; 96: 500-502, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32470602

RESUMO

No effective treatment for COVID-19 has been well established yet. Nafamostat, known as anticoagulant, has potential anti-inflammatory and anti-viral activities against COVID-19. We report three cases of COVID-19 pneumonia who progressed while using antiviral drugs and needed supplementary oxygen therapy, improved after treatment with nafamostat. These preliminary findings show the possibility that Nafamostat can be considered to be used in elderly patients with COVID-19 pneumonia who need oxygen therapy. The effectiveness of nafamostat should be evaluated in further studies.


Assuntos
Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/terapia , Guanidinas/uso terapêutico , Oxigênio/uso terapêutico , Pneumonia Viral/terapia , Idoso , Humanos , Masculino , Pandemias , Resultado do Tratamento
12.
Br J Pharmacol ; 177(14): 3147-3161, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32368792

RESUMO

As of April 9, 2020, a novel coronavirus (SARS-CoV-2) had caused 89,931 deaths and 1,503,900 confirmed cases worldwide, which indicates an increasingly severe and uncontrollable situation. Initially, little was known about the virus. As research continues, we now know the genome structure, epidemiological and clinical characteristics, and pathogenic mechanisms of SARS-CoV-2. Based on this knowledge, potential targets involved in the processes of virus pathogenesis need to be identified, and the discovery or development of drugs based on these potential targets is the most pressing need. Here, we have summarized the potential therapeutic targets involved in virus pathogenesis and discuss the advances, possibilities, and significance of drugs based on these targets for treating SARS-CoV-2. This review will facilitate the identification of potential targets and provide clues for drug development that can be translated into clinical applications for combating SARS-CoV-2.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/uso terapêutico , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Antivirais/uso terapêutico , Basigina/metabolismo , Betacoronavirus/metabolismo , Betacoronavirus/patogenicidade , Infecções por Coronavirus/complicações , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/terapia , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/etiologia , Síndrome da Liberação de Citocina/imunologia , Gabexato/análogos & derivados , Gabexato/uso terapêutico , Genoma Viral , Guanidinas/uso terapêutico , Humanos , Imunização Passiva , Imunossupressores/uso terapêutico , Medicina Tradicional Chinesa , Inibidores da Síntese de Ácido Nucleico/uso terapêutico , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/complicações , Pneumonia Viral/imunologia , Pneumonia Viral/metabolismo , Inibidores de Proteases/uso terapêutico , RNA Replicase/metabolismo , Serina Endopeptidases/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo , Vacinas Virais , Internalização do Vírus , Replicação Viral
13.
Tohoku J Exp Med ; 251(1): 27-30, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32448818

RESUMO

The number of patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly increased, although the WHO declared a pandemic. However, drugs that function against SARS-CoV-2 have not been established. SARS-CoV-2 has been suggested to bind angiotensin-converting enzyme 2, the receptor of the SARS coronavirus. SARS coronavirus and coronavirus 229E, the cause of the common cold, replicate through cell-surface and endosomal pathways using a protease, the type II transmembrane protease. To examine the effects of protease inhibitors on the replication of coronavirus 229E, we pretreated primary cultures of human nasal epithelial (HNE) cells with camostat or nafamostat, each of which has been used for the treatment of pancreatitis and/or disseminated intravascular coagulation. HNE cells were then infected with coronavirus 229E, and viral titers in the airway surface liquid of the cells were examined. Pretreatment with camostat (0.1-10 µg/mL) or nafamostat (0.01-1 µg/mL) reduced the titers of coronavirus 229E. Furthermore, a significant amount of type II transmembrane protease protein was detected in the airway surface liquid of HNE cells. Additionally, interferons have been reported to have antiviral effects against SARS coronavirus. The additive effects of interferons on the inhibitory effects of other candidate drugs to treat SARS-CoV-2 infection, such as lopinavir, ritonavir and favipiravir, have also been studied. These findings suggest that protease inhibitors of this type may inhibit coronavirus 229E replication in human airway epithelial cells at clinical concentrations. Protease inhibitors, interferons or the combination of these drugs may become candidate drugs to inhibit the replication of SARS-CoV-2.


Assuntos
Antivirais/farmacologia , Coronavirus Humano 229E/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Gabexato/análogos & derivados , Guanidinas/farmacologia , Pneumonia Viral/tratamento farmacológico , Inibidores de Proteases/farmacologia , Replicação Viral/efeitos dos fármacos , Betacoronavirus/efeitos dos fármacos , Células Cultivadas , Coronavirus Humano 229E/enzimologia , Coronavirus Humano 229E/fisiologia , Meios de Cultivo Condicionados , Células Epiteliais/virologia , Gabexato/farmacologia , Humanos , Mucosa Nasal/citologia , Pandemias , Cultura Primária de Células , Serina Endopeptidases/fisiologia , Glicoproteína da Espícula de Coronavírus/metabolismo , Carga Viral
14.
Pestic Biochem Physiol ; 165: 104554, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32359545

RESUMO

Dinotefuran (DTF) is a systemic neonicotinoid insecticide characterized by a tetrahydrofuran ring. In the present study, we examined the characteristics of DTF binding to native nicotinic acetylcholine receptors (nAChRs) expressed in the American cockroach Periplaneta americana using radioligand-binding methods. The Scatchard analysis, using [3H]imidacloprid (IMI), indicated that IMI has a single class of high-affinity binding sites in the P. americana nerve cord. In contrast, the Scatchard analysis using [3H]DTF indicated that DTF has two different classes of binding sites. Both DTF and IMI were found to bind to one of the classes, for which DTF showed low affinity. The other class, for which DTF showed high affinity, was localized in the abdominal nerve cord but not in the thoracic nerve cord. IMI showed low affinity for the high-affinity DTF binding sites. Our data suggest that DTF binds with high affinity to a nAChR subtype distinct from the high-affinity subtype for IMI. This difference might be responsible, at least in part, for the difference in resistance development to DTF and IMI in P. americana.


Assuntos
Baratas , Inseticidas , Periplaneta , Receptores Nicotínicos , Animais , Sítios de Ligação , Guanidinas , Neonicotinoides , Nitrocompostos
15.
Sci Total Environ ; 723: 138056, 2020 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-32224397

RESUMO

Neonicotinoids are the largest group of systemic insecticides worldwide and are most commonly applied as agricultural seed treatments. However, little is known about the extent to which farmland birds are exposed to these compounds during standard agricultural practices. This study uses winter cereal, treated with the neonicotinoid clothianidin, as a test system to examine patterns of exposure in farmland birds during a typical sowing period. The availability of neonicotinoid-treated seed was recorded post-sowing at 39 fields (25 farms), and camera traps were used to monitor seed consumption by wild birds in situ. The concentration of clothianidin in treated seeds and crop seedlings was measured via liquid chromatography-tandem mass spectrometry, and avian blood samples were collected from 11 species of farmland bird from a further six capture sites to quantify the prevalence and level of clothianidin exposure associated with seed treatments. Neonicotinoid-treated seeds were found on the soil surface at all but one of the fields surveyed at an average density of 2.8 seeds/m2. The concentration of clothianidin in seeds varied around the target application rate, whilst crop seedlings contained on average 5.9% of the clothianidin measured in seeds. Exposure was confirmed in 32% of bird species observed in treated fields and 50% of individual birds post-sowing; the median concentration recorded in positive samples was 12 ng/mL. Results here provide clear evidence that a variety of farmland birds are subject to neonicotinoid exposure following normal agricultural sowing of neonicotinoid-treated cereal seed. Furthermore, the widespread availability of seeds at the soil surface was identified as a primary source of exposure. Overall, these data are likely to have global implications for bird species and current agricultural policies where neonicotinoids are in use, and may be pertinent to any future risk assessments for systemic insecticide seed treatments.


Assuntos
Grão Comestível/química , Inseticidas/análise , Animais , Aves , Fazendas , Guanidinas/análise , Neonicotinoides , Nitrocompostos/análise , Sementes/química , Tiazóis
16.
Sci Total Environ ; 725: 138328, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32294586

RESUMO

The wide application of neonicotinoid insecticides in soil may affect soil microbial community, yet the information is limited. This study first reports the effects of thiamethoxam and dinotefuranon on soil microbial community. Soil from a forest land was collected and spiked with different nominal levels (0.02 mg kg-1, 0.2 mg kg-1 and 2.0 mg kg-1) of thiamethoxam and dinotefuran, respectively, and cultivated for 112 days. During the study, concentrations of the two neonicotinoids and their potential degradation products were monitored by LC-MS/MS. At day 112, the soils were analyzed for genetic profile by high-throughput sequencing and carbon metabolic profile by Biolog-ECO plate. The results showed that thiamethoxam and dinotefuran were both attenuated during the study with rate constants being 0.008-0.017 d-1 and 0.024-0.032 d-1, respectively, and biodegradation played an important role. As compared to the blank control, the exposure to the studied two neonicotinoids changed the microbial community, and the changes were influenced by both the type of neonicotinoid and the level of exposure. As compared to the blank control, the relative abundances of phyla Gemmatimonadetes and OD1 decreased under most exposed conditions, while the relative abundances of Chloroflexi and Nitrospirae increased under most exposed conditions. The community transition changed the functional potential, particularly carbon metabolism (mostly decreased) and nitrogen metabolism (mostly increased). As compared to the blank control, the utilization of total 31 carbon sources (including six categories) was increased under low exposure to thiamethoxam, but was decreased under all other exposed conditions. Low exposure to dinotefuran stimulated the utilization of three categories of carbon sources (amines, carbohydrates and phenolic compounds). Low exposure to both neonicotinoids increased the community diversity, while middle and high exposure to both neonicotinoids decreased the community diversity. These findings provide new insights into the effects of neonicotinoids on microbial community in soil.


Assuntos
Inseticidas/análise , Microbiota , Cromatografia Líquida , Guanidinas , Neonicotinoides , Nitrocompostos , Oxazinas , Solo , Espectrometria de Massas em Tandem , Tiametoxam , Tiazóis
17.
Am J Trop Med Hyg ; 102(6): 1210-1213, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32342849

RESUMO

Novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has become a public health emergency of international concern. This was first noted in Wuhan, Hubei Province, China, and since then has become widespread globally. We report a 71-year-old woman with documented viral shedding (based on reverse transcription-polymerase chain reaction (RT-PCR) testing) of SARS-CoV-2 for 60 days from the onset of symptoms (55 days from her first positive test and 36 days after complete resolution of symptoms). This is to our knowledge the longest duration of viral shedding reported to date. This case demonstrates that viral shedding after COVID-19 diagnosis can be prolonged.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Pneumonia Viral/diagnóstico por imagem , Eliminação de Partículas Virais , Idoso , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/isolamento & purificação , China , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Infecções por Coronavirus/terapia , Ciclopentanos/uso terapêutico , Oxigenação por Membrana Extracorpórea , Feminino , Guanidinas/uso terapêutico , Humanos , Indóis/uso terapêutico , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/virologia , Moxifloxacina/uso terapêutico , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Pneumonia Viral/terapia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento
18.
Sci Total Environ ; 720: 137692, 2020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-32325603

RESUMO

Nitrous oxide (N2O) emissions from pasture-based livestock systems represent 34% of Brazil's agricultural greenhouse gas emissions. The forage species Brachiaria humidicola is known for its biological nitrification inhibition (BNI) capacity and N2O emissions reduction ability from urine patches under tropical conditions. However, there is little information about the effect of BNI on N2O emission and ammonia (NH3) volatilisation in the subtropics. This study aimed to: (i) evaluate the potential of Brachiaria humidicola, compared with Panicum maximum (Jacq. cv. Áries; guinea grass), a broadly used grass (with no BNI capacity), to reduce N2O emissions under subtropical conditions; (ii) determine the efficacy of nitrification inhibitor dicyandiamide (DCD) to decrease N2O emissions; and (iii) determine the effect of brachiaria and DCD application on NH3 volatilisation. A field experiment was carried out using a Cambisol, where cattle urine ± DCD was applied to brachiaria and guinea grass. Over the 67-day measurement period, cumulative N2O emissions were 20% lower from urine patches in the brachiaria treatment (1138 mg N m-2, Emission factor = 1.06%) compared to guinea grass (1436 mg N m-2, Emission factor = 1.33%) (P < .10). A greenhouse experiment, using pots with the same treatments as in the field experiment, suggested that this could have been due to lower soil nitrate levels under brachiaria forage compared to guinea grass, indicating that BNI could be a possible mechanism for lower N2O emissions from brachiaria. The DCD application was effective in both forage species, decreasing N2O emissions by 40-50% (P < .10) compared with the urine only treatment. Approximately 25% of the urine applied N was lost via NH3 volatilisation, however the NH3 loss was not affected by forage species or DCD application (P > .10). Overall, the results demonstrated that brachiaria and DCD use are strategies that can reduce N2O emissions from urine patches.


Assuntos
Brachiaria , Agricultura , Poluentes Atmosféricos , Amônia , Animais , Brasil , Bovinos , Fertilizantes , Guanidinas , Óxido Nitroso , Solo
19.
Chem Biol Interact ; 324: 109087, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32294457

RESUMO

Despite advances in cancer treatment modalities, DNA still stands as one of the targets for anticancer agents. DNA minor groove binders (MGBs) represent an important investigational chemotherapeutic class with promising cytotoxic capacity. Herein this study reports the potent cytotoxic effect of a series of repurposed flexible bis-imidamides 1-4, triaryl bis-guanidine 5 and bis-N-substituted guanidines 6,7 having a 1,4-diphenoxybenzene scaffold backbone on MCF-7 and MDA-MB-231 breast cancer cell lines. Of these compounds, imidamide 4 was chosen for further in-vitro, in-vivo and molecular dynamics (MD) studies owing to its promising anti-tumor activity, with IC50 values on MCF-7 and MDA-MB-231 breast cancer cell lines of 1.9 and 2.08 µM, respectively. Annexin V/propidium iodide apoptosis assay revealed apoptosis induction on imidamide 4 treated MCF-7 cells. RT-PCR assay results demonstrated the proapoptotic effect of compound 4 through increase of mRNA levels of the pro-apoptotic genes; p53, PUMA, and Bax, and inhibiting the anti-apoptotic Bcl-2 gene expression in MCF-7 cells. Moreover, compound 4 induced a G0/G1 cell-cycle arrest in MCF-7 in a dose-dependent manner. Corroborating in-vivo experiments on Ehrlich ascites carcinoma (EAC)-bearing mice, reflected the anticancer strength of derivative 4. For further target validation, molecular dynamics (MD) studies demonstrated an energetically favorable binding of imidamide 4 with the DNA minor groove AT rich site. In effect, imidamide 4 can be viewed as a promising hit dicationic compound with good cytotoxic and apoptotic inducing activity against breast cancer that can be adopted for future optimization.


Assuntos
Antineoplásicos/uso terapêutico , Antioxidantes/uso terapêutico , Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , DNA/metabolismo , Guanidinas/uso terapêutico , Animais , Antineoplásicos/química , Antineoplásicos/metabolismo , Antioxidantes/química , Antioxidantes/metabolismo , Carcinoma de Ehrlich/tratamento farmacológico , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Guanidinas/química , Guanidinas/metabolismo , Humanos , Fígado/patologia , Camundongos , Simulação de Dinâmica Molecular , Estrutura Molecular , Relação Estrutura-Atividade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA