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1.
PLoS One ; 15(7): e0229052, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32614853

RESUMO

Rice paddy irrigation ponds can sustain surprisingly high taxonomic richness and make significant contributions to regional biodiversity. We evaluated the impacts of pesticides and other environmental stressors (including eutrophication, decreased macrophyte coverage, physical habitat destruction, and invasive alien species) on the taxonomic richness of freshwater animals in 21 irrigation ponds in Japan. We sampled a wide range of freshwater animals (reptiles, amphibians, fishes, mollusks, crustaceans, insects, annelids, bryozoans, and sponges) and surveyed environmental variables related to pesticide contamination and other stressors listed above. Statistical analyses comprised contraction of highly correlated environmental variables, best-subset model selection, stepwise model selection, and permutation tests. Results showed that: (i) probenazole (fungicide) was a significant stressor on fish (i.e., contamination with this compound had a significantly negative correlation with fish taxonomic richness), (ii) the interaction of BPMC (insecticide; also known as fenobucarb) and bluegill (invasive alien fish) was a significant stressor on a "large insect" category (Coleoptera, Ephemeroptera, Hemiptera, Lepidoptera, Odonata, and Trichoptera), (iii) the interaction of BPMC and concrete bank protection was a significant stressor on an "invertebrate" category, (iv) the combined impacts of BPMC and the other stressors on the invertebrate and large insect categories resulted in an estimated mean loss of taxonomic richness by 15% and 77%, respectively, in comparison with a hypothetical pond with preferable conditions.


Assuntos
Invertebrados/efeitos dos fármacos , Praguicidas/toxicidade , Animais , Biodiversidade , Carbamatos/toxicidade , Ecossistema , Monitoramento Ambiental , Espécies Introduzidas , Invertebrados/fisiologia , Tanques , Tiazóis/toxicidade , Vertebrados/fisiologia
2.
Chemosphere ; 255: 127013, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32679631

RESUMO

In order to obtain higher agricultural yields, the use of chemical substances has been increased to prevent the proliferation of pests, as well as ensuring durability in the storage of the food produced. Such substances are known as pesticides that may well present risks to human health and the environment. In the presence of metal ions, these substances can interact forming new species with different characteristics. Carbendazim (MBC) is an example of a harmful pesticide, which has atoms of nitrogen and oxygen in its structure that can form complexes with metal ions. Thus, in this work has studied the interaction between the copper (II) metal ion and carbendazim and its formation in natural water. The Cu-MBC complex showed a reduction peak of 0.007 V and an oxidation peak of 0.500 V, with characteristics of a quasi-reversible process under a glassy carbon electrode. By anodic stripping voltammetry, a different behavior was observed in the interaction of copper and carbendazim in ultrapure water and Billings dam water; however, it was possible to observe the complex in both samples. Carbendazim in the presence of the metal shows lower oxidation potential value, indicating the influence of the metal on the electrochemical response of the pesticide.


Assuntos
Benzimidazóis/química , Carbamatos/química , Cobre/química , Poluentes Químicos da Água/química , Carbono/química , Técnicas Eletroquímicas/métodos , Eletrodos , Oxirredução
4.
Ecotoxicol Environ Saf ; 201: 110729, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32485491

RESUMO

The transformation of carbosulfan (CSN) in apples was investigated during oven-drying, microwave drying, and sun-drying. CSN transformed primarily into carbofuran (COA) during these drying processes. The conversion kinetics of CSN and COA was fitted by curve regression and mainly conformed to quadratic models (R2 = 0.70-0.97). Oven-drying promoted the transformation of CSN into COA. Microwave drying resulted in the highest scavenging capacity against CSN and COA (41%-100%). Moreover, a transformation mechanism was proposed on the basis of density functional theory (DFT) calculation. The COA originated from a series of chemical reactions involving hydroxyl substitution, cleavage, and oxidation; this result was further confirmed on the basis of molecular electrostatic potential (MEP) and molecular orbital theory. Furthermore, the toxicity and stability of CSN and COA were evaluated with the T.E.S.T. program. COA was less toxic than CSN to aquatic organisms but more toxic than CSN to rats. Therefore, COA production should be avoided during drying. Microwave drying was found to be the optimum choice for drying apples.


Assuntos
Carbamatos/metabolismo , Dessecação/métodos , Manipulação de Alimentos/métodos , Malus/química , Animais , Organismos Aquáticos/efeitos dos fármacos , Carbamatos/química , Carbamatos/toxicidade , Carbofurano/química , Carbofurano/metabolismo , Carbofurano/toxicidade , Dessecação/instrumentação , Manipulação de Alimentos/instrumentação , Depuradores de Radicais Livres/análise , Ratos
5.
J Environ Sci Health B ; 55(8): 726-731, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32558617

RESUMO

It is crucial to develop practical procedures for the control and reduction of pesticide residues in oil productions from farm to dining table. In this study, the dissipation behaviors of typical fungicide from rapeseed to oil production were studied to reveal relationship among spraying stage, application dosage, household oil processing stage, and pesticide residues. In the field trials, rape plants were sprayed with carbendazim at three different dosages during flowering period. Transfer assessment of carbendazim residues from rapeseed to oil production during household oil processing via different press techniques was determined using high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). The recoveries of carbendazim in rapeseed samples, meals after squeezing samples, and rapeseed oil samples ranged from 82.5% to 93.6% with relative standard deviations (RSDs) <5.2%. The validation results illustrated that the methods were reliable and sensitive. The average processing factor (PF) during household oil processing via hot press technique and cold press technique was 0.15 and 0.51, respectively. This study demonstrated that household oil processing could significantly reduce the pesticide residues, especially by hot press technique.


Assuntos
Benzimidazóis/análise , Carbamatos/análise , Contaminação de Alimentos/análise , Manipulação de Alimentos/métodos , Resíduos de Praguicidas/análise , Óleo de Brassica napus/análise , Brassica napus/química , Cromatografia Líquida de Alta Pressão/métodos , Características da Família , Fungicidas Industriais/análise , Óleo de Brassica napus/química , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/métodos
6.
Sci Total Environ ; 738: 139635, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-32534282

RESUMO

The use of synthetic pesticides in agriculture is increasingly debated. However, few studies have compared the impact of synthetic pesticides and alternative biopesticides on non-target soil microorganisms playing a central role in soil functioning. We conducted a mesocosm experiment and used high-throughput amplicon sequencing to test the impact of a fungal biopesticide and a synthetic fungicide on the diversity, the taxonomic and functional compositions, and co-occurrence patterns of soil bacterial, fungal and protist communities. Neither the synthetic pesticide nor the biopesticide had a significant effect on microbial α-diversity. However, both types of pesticides decreased the complexity of the soil microbial network. The two pesticides had contrasting impacts on the composition of microbial communities and the identity of key taxa as revealed by microbial network analyses. The biopesticide impacted keystone taxa that structured the soil microbial network. The synthetic pesticide modified biotic interactions favouring taxa that are less efficient at degrading organic compounds. This suggests that the biopesticides and the synthetic pesticide have different impact on soil functioning. Altogether, our study shows that pest management products may have functionally significant impacts on the soil microbiome even if microbial α-diversity is unaffected. It also illustrates the potential of high-throughput sequencing analyses to improve the ecotoxicological risk assessment of pesticides on non-target soil microorganisms.


Assuntos
Fungicidas Industriais , Solo , Biodiversidade , Agentes de Controle Biológico , Carbamatos , Compostos Organofosforados , Microbiologia do Solo
7.
Environ Pollut ; 265(Pt B): 114992, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32563121

RESUMO

The presence of pesticide in water resources is a topical issue in France as in many other countries. Resources can be contaminated by current-used pesticides and their metabolites but also by molecules banned 50 years ago. The number of reported studies on the impact of these substances on human health and environment increases every day. Currently, pesticides and their relevant degradation products are subjected to the European regulation for water intended for human consumption. It sets an individual quality limit of 0.1 µg/L, and another of 0.5 µg/L for the sum of their concentrations. The constant improvement of analytical methods allows laboratories to detect pesticides, at lower and lower concentrations but also more and more metabolites. However, regulation does not provide a national indicative metabolites list to be monitored. Each regional health agency offers their own list based on local agricultural practices and quantities of pesticides sold. This article reports a prioritization method allowing to identify new metabolites to be monitored in water resources, along drinking water treatment plants and in treated water; it describes its application in France in order to anticipate possible non-compliance with raw water and treated water and to provide solutions upstream of changes in sanitary control. This methodology has been developed to rank pesticides and to select the corresponding metabolites by combining three main criteria: use (sale and type of use), toxicity, and environmental fate (based on physical and chemical properties). Prioritization method was applied to four families of pesticides: carbamates, organophosphorus compounds, phenylpyrazoles and neonicotinoids, for which there is a real lack of knowledge as regards the occurrence of their metabolites in metropolitan France. 146 pesticides have been prioritized. The first 50 molecules were considered allowing the identification of 72 metabolites to be monitored in water resources and along drinking water treatment plants.


Assuntos
Praguicidas/análise , Poluentes Químicos da Água/análise , Carbamatos , Monitoramento Ambiental , França , Humanos , Neonicotinoides , Compostos Organofosforados , Recursos Hídricos
8.
Cochrane Database Syst Rev ; 6: CD012906, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32501595

RESUMO

BACKGROUND: Worldwide, there is an increasing incidence of type 2 diabetes mellitus (T2DM). Metformin is still the recommended first-line glucose-lowering drug for people with T2DM. Despite this, the effects of metformin on patient-important outcomes are still not clarified. OBJECTIVES: To assess the effects of metformin monotherapy in adults with T2DM. SEARCH METHODS: We based our search on a systematic report from the Agency for Healthcare Research and Quality, and topped-up the search in CENTRAL, MEDLINE, Embase, WHO ICTRP, and ClinicalTrials.gov. Additionally, we searched the reference lists of included trials and systematic reviews, as well as health technology assessment reports and medical agencies. The date of the last search for all databases was 2 December 2019, except Embase (searched up 28 April 2017). SELECTION CRITERIA: We included randomised controlled trials (RCTs) with at least one year's duration comparing metformin monotherapy with no intervention, behaviour changing interventions or other glucose-lowering drugs in adults with T2DM. DATA COLLECTION AND ANALYSIS: Two review authors read all abstracts and full-text articles/records, assessed risk of bias, and extracted outcome data independently. We resolved discrepancies by involvement of a third review author. For meta-analyses we used a random-effects model with investigation of risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, using 95% confidence intervals (CIs) for effect estimates. We assessed the overall certainty of the evidence by using the GRADE instrument. MAIN RESULTS: We included 18 RCTs with multiple study arms (N = 10,680). The percentage of participants finishing the trials was approximately 58% in all groups. Treatment duration ranged from one to 10.7 years. We judged no trials to be at low risk of bias on all 'Risk of bias' domains. The main outcomes of interest were all-cause mortality, serious adverse events (SAEs), health-related quality of life (HRQoL), cardiovascular mortality (CVM), non-fatal myocardial infarction (NFMI), non-fatal stroke (NFS), and end-stage renal disease (ESRD). Two trials compared metformin (N = 370) with insulin (N = 454). Neither trial reported on all-cause mortality, SAE, CVM, NFMI, NFS or ESRD. One trial provided information on HRQoL but did not show a substantial difference between the interventions. Seven trials compared metformin with sulphonylureas. Four trials reported on all-cause mortality: in three trials no participant died, and in the remaining trial 31/1454 participants (2.1%) in the metformin group died compared with 31/1441 participants (2.2%) in the sulphonylurea group (very low-certainty evidence). Three trials reported on SAE: in two trials no SAE occurred (186 participants); in the other trial 331/1454 participants (22.8%) in the metformin group experienced a SAE compared with 308/1441 participants (21.4%) in the sulphonylurea group (very low-certainty evidence). Two trials reported on CVM: in one trial no CVM was observed and in the other trial 4/1441 participants (0.3%) in the metformin group died of cardiovascular reasons compared with 8/1447 participants (0.6%) in the sulphonylurea group (very low-certainty evidence). Three trials reported on NFMI: in two trials no NFMI occurred, and in the other trial 21/1454 participants (1.4%) in the metformin group experienced a NFMI compared with 15/1441 participants (1.0%) in the sulphonylurea group (very low-certainty evidence). One trial reported no NFS occurred (very low-certainty evidence). No trial reported on HRQoL or ESRD. Seven trials compared metformin with thiazolidinediones (very low-certainty evidence for all outcomes). Five trials reported on all-cause mortality: in two trials no participant died; the overall RR was 0.88, 95% CI 0.55 to 1.39; P = 0.57; 5 trials; 4402 participants). Four trials reported on SAE, the RR was 0,95, 95% CI 0.84 to 1.09; P = 0.49; 3208 participants. Four trials reported on CVM, the RR was 0.71, 95% CI 0.21 to 2.39; P = 0.58; 3211 participants. Three trial reported on NFMI: in two trials no NFMI occurred and in one trial 21/1454 participants (1.4%) in the metformin group experienced a NFMI compared with 25/1456 participants (1.7%) in the thiazolidinedione group. One trial reported no NFS occurred. No trial reported on HRQoL or ESRD. Three trials compared metformin with dipeptidyl peptidase-4 inhibitors (one trial each with saxagliptin, sitagliptin, vildagliptin with altogether 1977 participants). There was no substantial difference between the interventions for all-cause mortality, SAE, CVM, NFMI and NFS (very low-certainty evidence for all outcomes). One trial compared metformin with a glucagon-like peptide-1 analogue (very low-certainty evidence for all reported outcomes). There was no substantial difference between the interventions for all-cause mortality, CVM, NFMI and NFS. One or more SAEs were reported in 16/268 (6.0%) of the participants allocated to metformin compared with 35/539 (6.5%) of the participants allocated to a glucagon-like peptide-1 analogue. HRQoL or ESRD were not reported. One trial compared metformin with meglitinide and two trials compared metformin with no intervention. No deaths or SAEs occurred (very low-certainty evidence) no other patient-important outcomes were reported. No trial compared metformin with placebo or a behaviour changing interventions. Four ongoing trials with 5824 participants are likely to report one or more of our outcomes of interest and are estimated to be completed between 2018 and 2024. Furthermore, 24 trials with 2369 participants are awaiting assessment. AUTHORS' CONCLUSIONS: There is no clear evidence whether metformin monotherapy compared with no intervention, behaviour changing interventions or other glucose-lowering drugs influences patient-important outcomes.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Adulto , Carbamatos/efeitos adversos , Carbamatos/uso terapêutico , Doenças Cardiovasculares/mortalidade , Causas de Morte , Diabetes Mellitus Tipo 2/mortalidade , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Peptídeo 1 Semelhante ao Glucagon/análogos & derivados , Humanos , Hipoglicemiantes/efeitos adversos , Insulina/uso terapêutico , Metformina/efeitos adversos , Infarto do Miocárdio/epidemiologia , Piperidinas/efeitos adversos , Piperidinas/uso terapêutico , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Acidente Vascular Cerebral/epidemiologia , Compostos de Sulfonilureia/efeitos adversos , Compostos de Sulfonilureia/uso terapêutico
9.
J Am Mosq Control Assoc ; 36(1): 16-21, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32497478

RESUMO

Commercial aerosolized insecticides can be implemented as a community-based approach to targeted indoor residual spraying against Aedes aegypti, but their efficacy on pyrethroid-resistant mosquitoes has not yet been evaluated. Two commercial aerosolized products (H24 Poder Fulminante Ultra Eficaz®, carbamate, and Baygon Ultra Verde®, pyrethroid) were sprayed on common indoor surfaces e.g., cement, plywood, and cloth, and tested for their residual efficacy on susceptible and field-derived pyrethroid-resistant Ae. aegypti strains using the WHO cone bioassays. Overall, ≥80% 24-h mortality was observed for both products for at least 4 wk regardless of the mosquito strain or surface type used. H24 Poder Fulminante Ultra Eficaz showed the highest residual potency, sustaining >80% mortality for 7-wk posttreatment regardless of mosquito strain and surface type. For Baygon Ultra Verde, the mean mortality of female Ae. aegypti remained >80% for a shorter period (4-6 wk). Nonpyrethroid commercial aerosolized formulations can provide a lasting residual effect indoors compatible with the need for rapid and lasting mosquito control during outbreaks and may be suitable for community-based targeted indoor residual spraying.


Assuntos
Aedes , Carbamatos , Inseticidas , Controle de Mosquitos , Piretrinas , Animais , Feminino , México , Resíduos de Praguicidas
10.
Mol Pharmacol ; 98(2): 156-167, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32591477

RESUMO

The natural product (+)-discodermolide (DDM) is a microtubule stabilizing agent and potent inducer of senescence. We refined the structure of DDM and evaluated the activity of novel congeners in triple negative breast and ovarian cancers, malignancies that typically succumb to taxane resistance. Previous structure-activity analyses identified the lactone and diene as moieties conferring anticancer activity, thus identifying priorities for the structural refinement studies described herein. Congeners possessing the monodiene with a simplified lactone had superior anticancer efficacy relative to taxol, particularly in resistant models. Specifically, one of these congeners, B2, demonstrated 1) improved pharmacologic properties, specifically increased maximum response achievable and area under the curve, and decreased EC50; 2) a uniform dose-response profile across genetically heterogeneous cancer cell lines relative to taxol or DDM; 3) reduced propensity for senescence induction relative to DDM; 4) superior long-term activity in cancer cells versus taxol or DDM; and 5) attenuation of metastatic characteristics in treated cancer cells. To contrast the binding of B2 versus DDM in tubulin, X-ray crystallography studies revealed a shift in the position of the lactone ring associated with removal of the C2-methyl and C3-hydroxyl. Thus, B2 may be more adaptable to changes in the taxane site relative to DDM that could account for its favorable properties. In conclusion, we have identified a DDM congener with broad range anticancer efficacy that also has decreased risk of inducing chemotherapy-mediated senescence. SIGNIFICANCE STATEMENT: Here, we describe the anticancer activity of novel congeners of the tubulin-polymerizing molecule (+)-discodermolide. A lead molecule is identified that exhibits an improved dose-response profile in taxane-sensitive and taxane-resistant cancer cell models, diminished risk of chemotherapy-mediated senescence, and suppression of tumor cell invasion endpoints. X-ray crystallography studies identify subtle changes in the pose of binding to ß-tubulin that could account for the improved anticancer activity. These findings support continued preclinical development of discodermolide, particularly in the chemorefractory setting.


Assuntos
Alcanos/química , Carbamatos/química , Lactonas/síntese química , Neoplasias Ovarianas/metabolismo , Pironas/química , Neoplasias de Mama Triplo Negativas/metabolismo , Moduladores de Tubulina/síntese química , Células A549 , Área Sob a Curva , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Humanos , Lactonas/química , Lactonas/farmacologia , Estrutura Molecular , Neoplasias Ovarianas/tratamento farmacológico , Taxoides/farmacologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Moduladores de Tubulina/química , Moduladores de Tubulina/farmacologia
11.
J Chromatogr A ; 1623: 461174, 2020 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-32505278

RESUMO

A new class of chitosan derivatives with an isopropylthiourea at the 2-position and various carbamates at the 3,6-positions of the glucosamine skeleton was synthesized by the selective thiocarbamoylation of the 2-amino group. The chiral stationary phases (CSPs) were then prepared by coating the obtained chitosan 2-isopropylthiourea-3,6-dicarbamate derivatives onto silica gel. The enantioseparation property of the chitosan-based CSPs was assessed with twelve racemates by high-performance liquid chromatography (HPLC). The CSPs displayed a characteristic enantioseparation power, which seemed to be significantly affected by the 3,6-substituents of the glucosamine unit. The chitosan derivatives with the 3,6-diphenylcarbamate, except for 2-methylphenylcarbamate, possessed higher enantioseparation abilities than those with the 3,6-dicyclohexylcarbamate. Compared to other chitosan derivatives with 2-various substituents and commercialized Chiralcel OD, the chitosan 2-isopropylthiourea derivatives revealed a relatively higher enantioselectivity for some racemic compounds.


Assuntos
Quitosana/análogos & derivados , Cromatografia Líquida de Alta Pressão/métodos , Carbamatos/química , Celulose/análogos & derivados , Celulose/química , Glucosamina/química , Fenilcarbamatos/química , Sílica Gel/química , Estereoisomerismo , Tioureia/análogos & derivados
13.
Sci Total Environ ; 739: 140081, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32554111

RESUMO

Carbendazim (CBZ) as a broad spectrum fungicide is widely used in the whole world to contorl plant diseases. With the application of CBZ in the agriculture, it has been detected in vegetables and fruits. Nowadays, it even has been detected in the watercourse and indoor dust. However, the toxic effects of CBZ on aquatic organisms have received limited attention. In this study, male adult zebrafish were exposed at 0, 30 and 100 µg/L CBZ for 21 days to assess its effects on hepatic glycolipid metabolism. After exposure, the body weight and length decreased, but the condition factor increased significantly. Some hepatic biochemical parameters including the levels of glucose, pyruvate, low density lipoprotein (LDL) and triglyceride (TG) decreased significantly in the liver of zebrafish after exposure with CBZ. Two transaminases alanine transaminase (ALT) and aspartate transaminase (AST) also increased significantly, indicating that subchronic CBZ exposure influenced the liver function. Moreover, the relative mRNA levels of some key genes related to the glycolysis and lipid metabolism in the liver also changed significantly. Furthermore, the transcriptome analysis showed that the carbon metabolism, lipid metabolism and detoxification metabolism were also affected in the liver of CBZ exposed zebrafish. Interestingly, we also found the amounts of the Firmicutes, Bacteroidetes, Actinobacteria, α-Proteobacteria, γ-Proteobacteria and Verrucomicrobia at phylum level significantly decreased in the gut. Sequencing V3-V4 region of 16S rRNA also demonstrated gut microbiota composition changed significantly according to weighted UniFrac distance analysis. Consequently, subchronic CBZ exposure induced hepatic metabolic disorder accompanied by gut microbiota dysbiosis in adult male zebrafish.


Assuntos
Disbiose , Microbioma Gastrointestinal , Animais , Benzimidazóis , Carbamatos , Glicolipídeos , Metabolismo dos Lipídeos , Masculino , RNA Ribossômico 16S , Peixe-Zebra
14.
Food Chem ; 327: 127075, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32446026

RESUMO

The needing of rapid and sensitive detection method for pesticides is increasing, to facilitate its detection without complicated instruments. Herein, a novel paper-based senor was developed for the visual detection of three carbamate pesticides (metolcarb, carbofuran, and carbaryl) based on CdTe quantum dots (QDs) and nano zinc 5, 10, 15, 20-tetra(4-pyridyl)-21H-23H-porphine (nano ZnTPyP) with a "turn-off-on" mode. This fluorescence sensing model could be applied in the highly selective and sensitive detection of carbamate pesticides both by fluorescence spectrometry or paper-based sensors. Based on the extracted RGB color values of paper, the partial least squares regression (PLSR) was used to accurately quantify the concentrations of carbamate pesticides in different food matrices (apple, cabbage and tea water). This method featured in high speed, low price and high accuracy, and provided a new strategy for the detection of food safety.


Assuntos
Compostos de Cádmio/química , Carbamatos/análise , Análise de Alimentos , Resíduos de Praguicidas/análise , Porfirinas/química , Pontos Quânticos , Telúrio/química , Fluorescência , Alimentos , Limite de Detecção , Nanoestruturas , Espectrometria de Fluorescência
15.
Neurology ; 94(22): e2311-e2322, 2020 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-32409485

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of adjunctive cenobamate 200 mg/d in patients with uncontrolled focal (partial-onset) seizures despite treatment with 1 to 3 antiepileptic drugs. METHODS: In this multicenter, double-blind, placebo-controlled study, adults 18 to 65 years of age with focal seizures were randomized 1:1 (cenobamate:placebo) after an 8-week baseline period. The 12-week double-blind treatment period consisted of a 6-week titration phase and a 6-week maintenance phase. The primary outcome was percent change in seizure frequency (from baseline) per 28 days during double-blind treatment. RESULTS: Two hundred twenty-two patients were randomized; 113 received cenobamate and 109 received placebo; and 90.3% and 90.8% of patients, respectively, completed double-blind treatment. Median baseline seizure frequency was 6.5 in 28 days (range 0-237). Compared to placebo, cenobamate conferred a greater median percent seizure reduction (55.6% vs 21.5%; p < 0.0001) The responder rate (≥50% reduction in seizure frequency) was 50.4% for cenobamate and 22.2% for placebo (p < 0.0001). Focal seizures with motor component, impaired awareness, and focal to bilateral tonic-clonic seizures were significantly reduced with cenobamate vs placebo. During maintenance, 28.3% of cenobamate-treated and 8.8% of placebo-treated patients were seizure-free. Treatment-emergent adverse events reported in >10% in either group (cenobamate vs placebo) were somnolence (22.1% vs 11.9%), dizziness (22.1% vs 16.5%), headache (12.4% vs 12.8%), nausea (11.5% vs 4.6%), and fatigue (10.6% vs 6.4%). CONCLUSION: Adjunctive treatment with cenobamate 200 mg/d significantly improved seizure control in adults with uncontrolled focal seizures and was well tolerated. CLINICALTRIALSGOV IDENTIFIER: NCT01397968. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that, for patients with uncontrolled focal seizures, adjunctive cenobamate reduces seizures.


Assuntos
Anticonvulsivantes/administração & dosagem , Carbamatos/administração & dosagem , Clorofenóis/administração & dosagem , Convulsões/diagnóstico , Convulsões/tratamento farmacológico , Tetrazóis/administração & dosagem , Adolescente , Adulto , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Convulsões/fisiopatologia , Adulto Jovem
16.
Sci Total Environ ; 731: 139136, 2020 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-32438087

RESUMO

The fungicide propamocarb (PM) is widely used to protect cucumbers, tomatoes and other plants from pathogens. According to previous studies, PM could be detected in the aquatic system in some area. However, the toxic effects of PM on zebrafish received very limited attention. In this study, we examined the toxic effects of various concentration of PM on the endpoints of development, locomotor behavior and oxidative stress in larval zebrafish. It was observed that PM exposure delayed embryonic development, inhibited hatchability at 60 and 72 h postfertilization and increased heart rate. After PM exposure, the larval zebrafish showed abnormal free swimming behavior and the swimming behavior in response to light-dark transition, indicating that PM had the potential to induce neurotoxicity. Moreover, PM exposure also affected the enzymatic activity of acetylcholinesterase and dopamine and the transcriptional level of genes related to neurotoxicity. In addition, PM exposure not only affects catalase (CAT), glutathione peroxidase (GPX), and glutathione S-transferase (GST) activity but also affects the transcription level of various genes. We believed that PM induced oxidative stress was also a possible reason to cause neurotoxicity in larval zebrafish. In summary, our results suggested that PM could disturb the endpoints at development, locomotor behavior and oxidative stress in larval zebrafish.


Assuntos
Fungicidas Industriais , Peixe-Zebra , Animais , Carbamatos , Embrião não Mamífero/efeitos dos fármacos , Larva , Estresse Oxidativo
17.
Chemosphere ; 255: 126871, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32413796

RESUMO

Research efforts into the potential side-effects of pesticides on beneficial organisms have focused on temperate test species and conditions. There is thus a need for studies into the ecotoxicity of a vaster range of pesticides under tropical conditions. The present study therefore aimed to compare the acute and chronic toxicity of the fungicide carbendazim to the earthworm Eisenia fetida under tropical and temperate conditions. To this end, laboratory toxicity tests were conducted with a tropical and European strain of E. fetida, using different artificial (OECD and TAS) and natural (LUFA and TNS) soils, and under different test temperatures (20 °C and 28 °C). In the acute lethality tests with artificial soils, the tropical strain of E. fetida was three to four order of magnitude less sensitive than the European strain, which is ascribed to the higher test temperature and (hence) higher microbial activity/pesticide degradation. The tropical strain was particularly sensitive in the tropical natural soil, which was attributed to the low pH (3.9) of this soil. The chronic toxicity tests overall also showed a lower sensitivity of the tropical strain on reproduction. These findings thus support the use of toxicity data generated under temperate conditions in tropical pesticide effect assessments. However, intensive agricultural practices in the tropics may dictate that exposure levels (and hence potentially also risks) are higher.


Assuntos
Benzimidazóis/toxicidade , Carbamatos/toxicidade , Fungicidas Industriais/toxicidade , Agricultura , Animais , Laboratórios , Oligoquetos/efeitos dos fármacos , Praguicidas/toxicidade , Solo/química , Poluentes do Solo/análise , Poluentes do Solo/toxicidade
18.
An Acad Bras Cienc ; 92(1): e20181021, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32401841

RESUMO

Fosamprenavir calcium is an amprenavir prodrug of the protease inhibitors class used in the treatment of patients with acquired immunodeficiency syndrome (AIDS). Different solid forms of this drug are described in patents, in this sense studies on the physico-chemical characterization and stability are relevant for the selection of a solid form with adequate features for pharmaceutical purposes. In the present work form I (commercial) and amorphous of fosamprenavir calcium were characterized by the techniques of Differential Scanning Calorimetry (DSC), Thermogravimetry (TGA), Powder X-ray Diffraction (PXRD), Fourier-Transform Infrared Spectroscopy (FTIR) and Scanning Electron Microscopy (SEM). Furthermore, the chemical and polymorphic stability of the commercial form were evaluated by DSC, PXRD, FTIR and High-Performance Liquid Chromatography (HPLC). In the studies of characterization, thermal analyses allied to spectroscopic methods (PXRD and FTIR) demonstrated that the presence of water in the crystalline structure of Form I is fundamental for maintaining its crystallinity. In studies of accelerated stability the techniques of DSC, PXRD and FTIR showed that Form I does not suffer phase change when submitted to controlled conditions of temperature and humidity. Moreover, HPLC and FTIR proved the chemical stability of this solid form of fosamprenavir, thus demonstrating its suitability for pharmaceutical purposes.


Assuntos
Carbamatos/química , Organofosfatos/química , Preparações Farmacêuticas/análise , Sulfonamidas/química , Tecnologia Farmacêutica/métodos , Umidade , Microscopia Eletrônica de Varredura , Análise Espectral/métodos , Temperatura , Termodinâmica
19.
Arch Virol ; 165(7): 1633-1639, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32356185

RESUMO

The aim of this work was assessment of the efficacy and tolerability of two different regimens for retreatment of hepatitis C virus (HCV) patients who failed to respond to SOF/DCV-based therapy. This prospective study included 104 HCV patients who failed to respond to SOF/DCV-based therapy. Patients were randomly allocated to two groups. Efficacy and tolerability were assessed. The 12-week sustained virological response (SVR12) rates were 96% and 94.4% in groups B and A, respectively, with no significant difference (p = 1.000). Most adverse events reported were mild to moderate, with no deaths during the study. Multi-target direct-acting antiviral (DAA) combinations are efficient for retreatment of HCV patients after failure of SOF/DCV-based therapy in real-world management.ClinicalTrials.gov identifier: NCT02992457.


Assuntos
Antivirais/administração & dosagem , Hepatite C Crônica/tratamento farmacológico , Adulto , Anilidas/administração & dosagem , Carbamatos/administração & dosagem , Quimioterapia Combinada , Feminino , Humanos , Imidazóis/administração & dosagem , Compostos Macrocíclicos/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Ribavirina/administração & dosagem , Ritonavir/administração & dosagem , Simeprevir/administração & dosagem , Sofosbuvir/administração & dosagem , Resultado do Tratamento
20.
Toxicology ; 440: 152490, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32418910

RESUMO

Testicular injury is often observed in drug development. Serum hormones are usually used as noninvasive biomarkers for testicular injury; however, their sensitivities are low. Therefore, it is difficult to monitor testicular injury in drug development. In recent years, molecules in body fluid exosomes have attracted attention as biomarkers for diseases. In this study, small RNAs in serum exosomes were analyzed to identify noninvasive biomarkers of testicular injury in rats, which are often used in preclinical drug development. The rat models of testicular injury were prepared by a single oral administration of 2000 mg/kg ethylene glycol monomethyl ether, in which spermatocyte degeneration and Sertoli cell vacuolation were observed, or 400 mg/kg carbendazim, in which Sertoli cell vacuolation and seminiferous tubule dilation were observed. Serum exosomal small RNA-seq analysis of these models was performed. The analysis identified 3 small RNAs that fluctuated in common between the models, and miR-423-5p and miR-128-3p were selected as candidate markers. For evaluating these candidate markers in other testicular injury models, the models were prepared by a single oral administration of 60 mg/kg 1,3-dinitrobenzene or 500 mg/kg nitrofurazone, and spermatocyte degeneration and Sertoli cell vacuolation were observed. In qPCR analysis, these exosomal miRNAs were upregulated in all models except for the 1,3-dinitrobenzene model, in which severe hemolysis was observed. By contrast, these miRNAs in whole serum extracts did not significantly change in any of the models. In conclusion, we identified miR-423-5p and miR-128-3p in serum exosomes as noninvasive biomarkers for testicular injury in rats.


Assuntos
Biomarcadores/análise , Exossomos/química , RNA Citoplasmático Pequeno/análise , Doenças Testiculares/diagnóstico , Animais , Benzimidazóis/toxicidade , Carbamatos/toxicidade , Dinitrobenzenos/toxicidade , Masculino , MicroRNAs/efeitos dos fármacos , Nitrofurazona/toxicidade , Ratos , Ratos Sprague-Dawley , Células de Sertoli/química , Células de Sertoli/patologia , Espermatócitos/química , Espermatócitos/efeitos dos fármacos , Vacúolos/efeitos dos fármacos , Vacúolos/patologia
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