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1.
Nature ; 580(7804): 511-516, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32322067

RESUMO

The taste of sugar is one of the most basic sensory percepts for humans and other animals. Animals can develop a strong preference for sugar even if they lack sweet taste receptors, indicating a mechanism independent of taste1-3. Here we examined the neural basis for sugar preference and demonstrate that a population of neurons in the vagal ganglia and brainstem are activated via the gut-brain axis to create preference for sugar. These neurons are stimulated in response to sugar but not artificial sweeteners, and are activated by direct delivery of sugar to the gut. Using functional imaging we monitored activity of the gut-brain axis, and identified the vagal neurons activated by intestinal delivery of glucose. Next, we engineered mice in which synaptic activity in this gut-to-brain circuit was genetically silenced, and prevented the development of behavioural preference for sugar. Moreover, we show that co-opting this circuit by chemogenetic activation can create preferences to otherwise less-preferred stimuli. Together, these findings reveal a gut-to-brain post-ingestive sugar-sensing pathway critical for the development of sugar preference. In addition, they explain the neural basis for differences in the behavioural effects of sweeteners versus sugar, and uncover an essential circuit underlying the highly appetitive effects of sugar.


Assuntos
Encéfalo/fisiologia , Comportamento de Escolha/fisiologia , Açúcares da Dieta/metabolismo , Preferências Alimentares/fisiologia , Glucose/metabolismo , Intestinos/fisiologia , Animais , Encéfalo/citologia , Açúcares da Dieta/química , Glucose/análogos & derivados , Glucose/química , Masculino , Metilglucosídeos/química , Metilglucosídeos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/fisiologia , Paladar/fisiologia , Tiazinas/metabolismo , Água/metabolismo
2.
Artigo em Inglês | MEDLINE | ID: mdl-32172174

RESUMO

Glyoxylic acid (GA) is the intermediate metabolite in various mammalian metabolic pathways. GA showed high reactivity towards formation of advanced glycation end-products (AGEs); the main cause of pathogenesis and complications of many diseases. The presented study aimed to detect GA in healthy and cardiovascular patients' (CV) sera; however analysis of GA in biological fluid is a challenge and requires chemical derivatization. Hence, a new, highly sensitive, time saving and reproducible pre-column fluorescence derivatization procedure coupled with high performance liquid chromatography (HPLC) method was developed. The derivatization method was based on reaction of 2-aminobenzenthiol (2-ABT), a fluorogenic reagent, with GA in acidic medium to form highly fluorescent thiazine derivative (290 and 390 nm for excitation and emission wavelengths respectively). The fluorescent derivative was separated within 6 min on a reversed-phase ODS column using an isocratic elution with a mixture of methanol-water (70:30, v/v%). The proposed method parameters were optimized and the method was validated. A good linearity in the concentration range (0.05-5.0 µM) was obtained with detection limit (LOD) of 10 nM (200 fmol/injection), which is more sensitive than several previous methods. Moreover, the recovery results were within the range of 85.0-95.5 % and the intra- and inter-day precision results were ≤3.5%. It should be emphasized that this method is the first one for monitoring of GA in CV patients; to investigate its role for diagnosis and monitoring the severity and complications of this disease in clinical laboratory.


Assuntos
Doenças Cardiovasculares/diagnóstico , Corantes Fluorescentes/química , Glioxilatos/sangue , Tiazinas/química , Adulto , Cromatografia Líquida de Alta Pressão , Feminino , Produtos Finais de Glicação Avançada/química , Humanos , Limite de Detecção , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Espectrometria de Fluorescência
3.
Arq Bras Oftalmol ; 83(2): 149-152, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32159596

RESUMO

Gyrate atrophy is a rare metabolic autosomal recessive disorder caused by ornithine aminotransferase enzyme deficiency that leads to characteristic progressive, degenerative chorioretinal findings. Patients complain mostly of low vision, night blindness, and peripheral vision loss. Posterior subcapsular cataract, myopia, choroid neovascularization, and intraretinal cysts may be accompanying factors related to vision loss. We encountered a patient with vision loss secondary to posterior subcapsular cataract and intraretinal cysts. After treatment with topical brinzolamide and nepafenac (and without any diet mo dification and/or supplementation), we observed 143- and 117-mm macular thickness resolutions with 2 and 1 Snellen lines of visual gain in his right and left eyes, respectively. Also, we detected a novel homozygous mutation in the ornithine aminotransferase gene: c.1253T>C (p.Leu418Pro). Carbonic anhydrase inhibitors and/or non-steroid anti-inflammatory drugs can control macular edema in patients with gyrate atrophy-associated intraretinal cysts. The genetic variants may also be a determinant in the responsiveness to the therapy type.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Benzenoacetamidas/administração & dosagem , Inibidores da Anidrase Carbônica/administração & dosagem , Atrofia Girata/genética , Edema Macular/tratamento farmacológico , Fenilacetatos/administração & dosagem , Sulfonamidas/administração & dosagem , Tiazinas/administração & dosagem , Administração Oftálmica , Adulto , Angiofluoresceinografia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Edema Macular/diagnóstico por imagem , Masculino , Mutação , Ornitina-Oxo-Ácido Transaminase/genética , Tomografia de Coerência Óptica
4.
Chemosphere ; 243: 125431, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31995882

RESUMO

Recently, artificial sweeteners have received widespread attention as the emerging environmental pollutants, among which, acesulfame (ACE) is ubiquitously present and extremely persistent in the ecosystem. Although the environmental behavior of ACE has already been well studied, its chronic eco-toxicological effects on aquatic organisms are rarely reported. Thus, more researches should be performed to determine the concentration which exerted the observable toxicological effect. Herein, we examined neuro-behavioral effects of ACE at 1, 10 and 100 mg/L on adult zebrafish via performing the behavioral test batteries including light/dark preference test, novel tank diving test, novel object exploration test, social preference test and colour-enhanced CPP test. In addition, in order to fully phenotype the behavioral alteration induced by ACE, we applied the techniques deriving from behavioral phenomics to analyze and interpret the big data from a large number of behavioral variables. Furthermore, the alterations of neurotransmitter in brain were also assayed to confirm the behavioral results. We found that ACE within the concentration range of No Observed Effect Concentrations (NOECs) had remarkably altered the neuro-behavioral profiles: altered the preference for light/dark, reduced the exploration ability of zebrafish in the novel tank and novel object exploration test, affected the group preference of zebrafish, changed the colour preference, learning and memory ability of zebrafish and disturbed the quantitative patterns of neurotransmitter in brain. As a result, this research can offer a reference for readjusting the NOECs of ACE and assessing neurotoxicity of artificial sweeteners.


Assuntos
Organismos Aquáticos/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Ecossistema , Tiazinas/farmacologia , Animais , Síndromes Neurotóxicas , Edulcorantes/farmacologia , Edulcorantes/toxicidade , Tiazinas/toxicidade , Peixe-Zebra
5.
AAPS PharmSciTech ; 21(2): 69, 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31950311

RESUMO

In the present work, a cost-effective, stable and sustained release ophthalmic solution formulation of brinzolamide (BRZ) was developed for the treatment of glaucoma. The prototype formulation undergoes 'in situ gelling' when administered in the eye, thereby providing longer residence (16-24 h). As a result, the same therapeutic endpoint is achieved with once daily dosing vis-à-vis the commercially available product Azopt® (brinzolamide 1.0% w/v, Alcon Laboratories, USA) that requires 3-4 times instillations per day. The prototype formulations were prepared using dimethyl sulfoxide, polyoxyl 35 castor oil and polysorbate 80. Gellan gum was used as the in situ gelling agent. Formulation variables like (i) concentration of the drug, dimethyl sulfoxide and in situ gelling agent and (ii) type and concentration of solubiliser showed a significant effect on the solubility of brinzolamide, in vitro gelling time, in vitro drug release and in situ gel stability. Prototype formulations were evaluated in New Zealand white rabbits for ocular toxicity and efficacy study. The tested formulations were well tolerated and reduced intraocular pressure (IOP) from 25-28 to 12-14 mmHg compared to saline and placebo control samples. Additionally, a significant increase in the area under change in IOP from baseline (ΔIOP) vs. time curve and a longer mean residence time (MRT) were also observed for the test formulations (7.4 to 17.7 h) compared to the commercially available suspension of Azopt® (4.9 h) (p < 0.0001). Thus, 'in situ gelling' formulation strategy described in this work can work as a viable option for ocular delivery of brinzolamide for the treatment of glaucoma.


Assuntos
Soluções Oftálmicas/química , Sulfonamidas/química , Tiazinas/química , Animais , Óleo de Rícino , Dimetil Sulfóxido , Composição de Medicamentos , Liberação Controlada de Fármacos , Excipientes , Géis , Glaucoma/induzido quimicamente , Glaucoma/tratamento farmacológico , Pressão Intraocular/efeitos dos fármacos , Masculino , Polissacarídeos Bacterianos , Polissorbatos , Coelhos , Sulfonamidas/administração & dosagem , Sulfonamidas/uso terapêutico , Tiazinas/administração & dosagem , Tiazinas/uso terapêutico
6.
Ecotoxicol Environ Saf ; 189: 109980, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31785946

RESUMO

Artificial sweeteners (ASs) are applied widely as sucrose substitutes in food, pharmaceuticals, and personal-care products, which results in their release into surface water. The occurrence of ASs in aquatic environments in China has rarely been reported. In this study, we determined the concentration of seven ASs in surface water and sediment samples from 16 lakes in Wuhan. The sum of the ASs concentration ranged from 0.89 to 20.6 µg/L in the surface water, with a mean value of 4.96 ± 5.16 µg/L. The most abundant AS was sucralose (SUC), with a concentration from 0.33 to 18.0 µg/L, followed by acesulfame (ACE) (0.40-2.78 µg/L), saccharin (SAC) (

Assuntos
Indicadores Ambientais , Sacarose/análogos & derivados , Edulcorantes/análise , Tiazinas/análise , Poluentes Químicos da Água/análise , China , Monitoramento Ambiental , Sedimentos Geológicos/química , Lagos/química , Estações do Ano , Sacarose/análise
7.
Environ Pollut ; 256: 113437, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31672357

RESUMO

Pesticides often occur as mixtures of complex compounds in water environments, while most of studies only focus on the toxic effects of individual pesticides with little attention to the joint toxic effects. In the present study, we aimed to the mixture toxicity of beta-cypermethrin (BCY) and thiacloprid (THI) to zebrafish (Danio rerio) employing multiple toxicological endpoints. Results displayed that the 96-h LC50 values of BCY to D. rerio at various developmental stages ranged from 2.64 × 10 (1.97 × 10-3.37 × 10) to 6.03 × 103 (4.54 × 103-1.05 × 104) nM, which were lower than those of THI ranging from 2.97 × 104 (1.96 × 104-4.25 × 104) to 2.86 × 105 (2.19 × 105-5.87 × 105) nM. Mixtures of BCY and THI exhibited synergistic response in embryonic zebrafish. Meanwhile, the enzyme activities of antioxidants (CAT and SOD) and detoxification enzyme (CarE), endogenous T-GSH and MDA contents, as well as gene expressions (tsh, crh, cxcl and bax) involved in oxidative stress, cellular apoptosis, immune system and endocrine system were obviously changed in the mixture exposure compared with the respective BCY or THI treatment. Consequently, the increased toxicity of pesticide mixture suggested that the toxicological data acquired from individual pesticide tests might underrate the toxicity risk of pesticides that actually arise in the real environment. Taken together, our present study provided evidence that mixture exposure of BCY and THI could induce additional toxic effect compared with their respective individual pesticides on D. rerio, offering valuable insights into the toxic mechanism of pesticide mixture.


Assuntos
Neonicotinoides/toxicidade , Praguicidas/toxicidade , Piretrinas/toxicidade , Tiazinas/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Embrião não Mamífero/metabolismo , Embrião não Mamífero/fisiologia , Expressão Gênica/efeitos dos fármacos , Larva/metabolismo , Estresse Oxidativo , Peixe-Zebra/embriologia , Peixe-Zebra/metabolismo
8.
Eur J Ophthalmol ; 30(2): 293-298, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30526051

RESUMO

AIM: To evaluate the effectiveness of brinzolamide-brimonidine fixed combination to control the intraocular pressure elevation throughout the first 24 h following uncomplicated phacoemulsification cataract surgery. PATIENTS AND METHODS: A total of 62 patients who underwent phacoemulsification cataract surgery were included in this prospective randomized comparative case series. The brinzolamide-brimonidine fixed combination group (34 eyes) was administered a single dose of brinzolamide-brimonidine fixed combination immediately after phacoemulsification. No treatment was administered in the control group (28 eyes). Intraocular pressure was measured 1 day before surgery (baseline) and at 6, 12 and 24 h postoperatively. RESULTS: The brinzolamide-brimonidine fixed combination group had significantly lower intraocular pressure at 6, 12 and 24 h after phacoemulsification compared to baseline (p < 0.0001 for all comparisons), while in control group, intraocular pressure was significantly higher at 6 and 12 h after surgery compared to baseline (p < 0.001 and p < 0.0001, respectively). In control group, an intraocular pressure elevation ⩾ 5 mm Hg was noted in 32.4% of the eyes at 6 and 12 h and in 5.9% of eyes at 24 h after surgery, while in brinzolamide-brimonidine fixed combination group, only 8.8% of the eyes at 6 h postoperatively had such an intraocular pressure elevation. CONCLUSION: The administration of a single drop of brinzolamide-brimonidine fixed combination effectively prevented intraocular pressure elevations and intraocular pressure spikes during the first 24 h after uneventful phacoemulsification.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/uso terapêutico , Tartarato de Brimonidina/uso terapêutico , Inibidores da Anidrase Carbônica/uso terapêutico , Pressão Intraocular/efeitos dos fármacos , Hipertensão Ocular/prevenção & controle , Facoemulsificação , Sulfonamidas/uso terapêutico , Tiazinas/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hipertensão Ocular/etiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos , Tonometria Ocular
9.
Food Chem ; 303: 125404, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31466033

RESUMO

Fourier transform infrared (FTIR) spectroscopy calibrations were developed to simultaneously determine the multianalytes of five artificial sweeteners, including sodium cyclamate, sucralose, sodium saccharin, acesulfame-K and aspartame. By combining the pretreatment of the spectrum and principal component analysis, 131 feature wavenumbers were extracted from the full spectral range for modelling to qualitative and quantitative analysis. Compared to random forest, k nearest neighbour and linear discriminant analysis, support vector machine model had better predictivity, indicating the most effective identification performance. Furthermore, multivariate calibration models based on partial least squares regression were constructed for quantifying any combinations of the five artificial sweeteners, and validated by prediction data sets. As shown by the good agreement between the proposed method and the reference HPLC for the determination of the sweeteners in beverage samples, a promising and rapid tool based on FTIR spectroscopy, coupled with chemometrics, has been performed to identify and objectively quantify artificial sweeteners.


Assuntos
Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Edulcorantes/análise , Aspartame/análise , Bebidas/análise , Calibragem , Cromatografia Líquida de Alta Pressão/métodos , Ciclamatos/análise , Aprendizado de Máquina , Análise de Componente Principal , Sacarina/análise , Tiazinas/análise
10.
Chemosphere ; 240: 124926, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31726586

RESUMO

Insect pollinators such as bees and syrphid flies play a crucial role in pollinating many food crops, and their diversity and abundance may be influenced by pesticide application patterns. Over three years, we assessed the ecotoxicological impacts on the diversity and abundance of bees and syrphid flies between reduced-risk pesticide programs and standard, conventional pesticide programs in paired plots at six spatially distinct commercial apple orchards. In particular, we quantified pesticide inputs, environmental impact, and community response of bees and syrphids to these pesticide programs. Relative environmental impacts of reduced-risk versus conventional pesticide programs were calculated using Environmental Impact Quotient analysis, while ecological impacts were characterized by assessing the abundance, richness, and species assemblages of bees and syrphids. Adopting a reduced-risk pesticide program for apple pest management reduced the use (in terms of kg a.i./ha) of organophosphate and pyrethroid insecticides by approximately 97.6% and 100% respectively, but increased the use of neonicotinoid pesticides (acetamiprid, imidacloprid, thiacloprid) by 40.4% compared to the orchards under standard conventional pesticide program. Regardless of pesticide inputs, abundance, richness and species assemblages of bees and syrphids did not differ between reduced-risk and conventional pest management programs. However, the environmental impact of pesticide inputs was reduced by 89.8% in reduced-risk pesticide program. These findings suggest that the implementation of reduced-risk pesticide program may reduce pesticide environmental impact, in addition to being safer to farm workers, without adversely affecting the robust community composition of bees and syrphids in commercial apple orchards in the mid-Atlantic region.


Assuntos
Produtos Agrícolas , Malus , Controle de Pragas/métodos , Praguicidas , Polinização , Animais , Abelhas , Ecotoxicologia , Meio Ambiente , Insetos , Inseticidas , Neonicotinoides , Nitrocompostos , Piretrinas , Tiazinas
11.
J Enzyme Inhib Med Chem ; 35(1): 31-41, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31645149

RESUMO

The present study describes the synthesis of a novel series of thiazolidin-4-one and thiazinan-4-one using 1-(2-aminoethyl)pyrrolidine as amine precursor. All compounds were synthesised by one-pot three component cyclocondensation reaction from the amine, a substituted benzaldehyde and a mercaptocarboxylic acid. The compounds were obtained in moderate to good yields and were identified and characterised by 1H, 13 C, 2 D NMR and GC/MS techniques. The compounds also were screened for their in vitro acetylcholinesterase (AChE) activity in hippocampus and cerebral cortex on Wistar rats. The six most potent compounds have been investigated for their cytotoxicity by cell viability assay of astrocyte primary culture, an important cell of central nervous system. We highlighted two compounds (6a and 6k) that had the lowest IC50 in hippocampus (5.20 and 4.46 µM) and cerebral cortex (7.40 and 6.83 µM). These preliminary and important results could be considered a starting point for the development of new AChE inhibitory agents.


Assuntos
Acetilcolinesterase/metabolismo , Inibidores da Colinesterase/farmacologia , Tiazinas/farmacologia , Tiazolidinas/farmacologia , Animais , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/enzimologia , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/química , Relação Dose-Resposta a Droga , Hipocampo/efeitos dos fármacos , Hipocampo/enzimologia , Estrutura Molecular , Ratos , Ratos Wistar , Relação Estrutura-Atividade , Tiazinas/síntese química , Tiazinas/química , Tiazolidinas/síntese química , Tiazolidinas/química
12.
Molecules ; 24(22)2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31726792

RESUMO

In this work, we present an automated luminescence sensor for the quantitation of the insecticide thiacloprid, one of the main neonicotinoids, in lettuce samples. A simple and automated manifold was constructed, using multicommutated solenoid valves to handle all solutions. The analyte was online irradiated with UV light to produce a highly fluorescent photoproduct (λexc/λem = 305/370 nm/nm) that was then retained on a solid support placed in the flow cell. In this way, the pre-concentration of the photoproduct was achieved in the detection area, increasing the sensitivity of the analytical method. A method-detection limit of 0.24 mg kg-1 was achieved in real samples, fulfilling the Maximum Residue Limit (MRL) of The European Union for thiacloprid in lettuce (1 mg kg-1). A sample throughput of eight samples per hour was obtained. Recovery experiments were carried out at values close to the MRL, obtaining recovery yields close to 100% and relative standard deviations lower than 5%. Hence, this method would be suitable for routine analyses in quality control, as an alternative to other existing methods.


Assuntos
Alface/química , Neonicotinoides/química , Compostos Fitoquímicos/química , Tiazinas/química , Concentração de Íons de Hidrogênio , Processos Fotoquímicos , Fotoquímica/métodos , Análise Espectral
13.
Analyst ; 144(21): 6172-6192, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31584044

RESUMO

Terahertz time-domain spectroscopy (THz-TDS) is a non-invasive, non-contact and label-free technique for biological and chemical sensing as THz-spectra are less energetic and lie in the characteristic vibration frequency regime of proteins and DNA molecules. However, THz-TDS is less sensitive for the detection of micro-organisms of size equal to or less than λ/100 (where, λ is the wavelength of the incident THz wave), and molecules in extremely low concentration solutions (like, a few femtomolar). After successful high-throughput fabrication of nanostructures, nanoantennas were found to be indispensable in enhancing the sensitivity of conventional THz-TDS. These nanostructures lead to strong THz field enhancement when in resonance with the absorption spectrum of absorptive molecules, causing significant changes in the magnitude of the transmission spectrum, therefore, enhancing the sensitivity and allowing the detection of molecules and biomaterials in extremely low concentration solutions. Herein, we review the recent developments in ultra-sensitive and selective nanogap biosensors. We have also provided an in-depth review of various high-throughput nanofabrication techniques. We also discussed the physics behind the field enhancements in the sub-skin depth as well as sub-nanometer sized nanogaps. We introduce finite-difference time-domain (FDTD) and molecular dynamics (MD) simulation tools to study THz biomolecular interactions. Finally, we provide a comprehensive account of nanoantenna enhanced sensing of viruses (like, H1N1) and biomolecules such as artificial sweeteners which are addictive and carcinogenic.


Assuntos
Vírus da Influenza A/isolamento & purificação , Nanoestruturas/química , Edulcorantes/análise , Espectroscopia Terahertz/métodos , Aspartame/análise , Simulação de Dinâmica Molecular , Proteínas/química , Tiazinas/análise
14.
Eur J Med Chem ; 184: 111756, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31630054

RESUMO

Human histone deacetylase 8 (HDAC8) is a highly promising target for neuroblastoma and other types of cancer. Several HDAC inhibitors are approved for the treatment of special cancer subtypes or are evaluated in clinical trials. By far the most drugs or drug candidates contain a hydroxamate group that chelates the catalytic zinc ion within HDACs. Most hydroxamate inhibitors are more or less unselective, although there are considerable exceptions demonstrating the general feasibility to develop at least HDAC isoenzyme selective inhibitors. In addition, hydroxamates have recently come under discussion regarding their potential for mutagenicity. Recently, PD-404,182 was discovered as a selective and potent non-hydroxamate inhibitor of HDAC8. However, this active compound turned out to be decomposed in the presence of glutathion (GSH). Here, we describe the synthesis of significantly improved analogs of PD-404,182 that demonstrate both, great selectivity for HDAC8 and also chemical stability in the presence of GSH. The compounds are characterized with respect to structure-activity relationship, binding mode and target engagement in neuroblastoma cells by combining biochemical and biophysical methods with chemoinformatics.


Assuntos
Inibidores de Histona Desacetilases/farmacologia , Proteínas Repressoras/antagonistas & inibidores , Tiazinas/farmacologia , Relação Dose-Resposta a Droga , Inibidores de Histona Desacetilases/síntese química , Inibidores de Histona Desacetilases/química , Histona Desacetilases/metabolismo , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Proteínas Repressoras/metabolismo , Relação Estrutura-Atividade , Tiazinas/síntese química , Tiazinas/química
15.
PLoS One ; 14(9): e0214702, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31539393

RESUMO

The cabbage stem flea beetle (CSFB), Psylliodes chrysocephala (Coleoptera: Chrysomelidae), has recently become a major pest species in winter oilseed rape in the Czech Republic. The susceptibility of CSFB populations from two localities to six pyrethroids, two neonicotinoids, one organophosphate and one oxadiazine was evaluated in 2015-2018 in glass vial experiments. The susceptibility of CSFB to thiacloprid and thiamethoxam was evaluated in feeding experiment in 2017 and 2018. High susceptibility of CSFB populations to lambda-cyhalothrin, cypermethrin, esfenvalerate, tau-fluvalinate, etofenprox, deltamethrin, chlorpyrifos, indoxacarb and acetamiprid was observed in the glass vial experiments. The LC50 and LC90 data obtained for pyrethroids in these experiments in 2015 represent baseline for CSFB resistance monitoring to pyrethroids in the Czech Republic. High tolerance of CSFB to thiacloprid of CSFB was demonstrated in glass vial and the feeding experiment, too.


Assuntos
Besouros/efeitos dos fármacos , Resistência a Inseticidas , Inseticidas/toxicidade , Neonicotinoides/toxicidade , Piretrinas/toxicidade , Tiazinas/toxicidade , Animais , Brassica/parasitologia , Besouros/patogenicidade
16.
Environ Sci Pollut Res Int ; 26(34): 34723-34740, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31520389

RESUMO

Among pesticides and foliar sprays involved in the treatment of seed, soil, and grass, also to crops, an important group is neonicotinoids. Neonicotinoid pesticides present similar properties with nicotine, but the mentioned compounds are less harmful for humans. Nevertheless, neonicotinoids are poisonous to insects and some invertebrates, which can act against insects' central nervous system, leading to their death. Moreover, neonicotinoids can affect the reproduction, foraging, and flying ability of honeybee and other insects including pollinators. In the present study, some neonicotinoids, such as imidacloprid, acetamiprid, clothianidin, thiacloprid, and thiamethoxam together with their toxic effects, have been presented. The Environmental Protection Agency (EPA) classifies these neonicotinoids as II and III class toxicity agents. Due to accumulation of these pesticides into the pollen of treated plants, especially due to their toxic effects against pollinators, the consequences of the occurrence of these insecticides have been discussed. Analytical aspects and methods involved in the isolation and determination of this class of pesticides have been presented in this contribution.


Assuntos
Inseticidas , Neonicotinoides , Animais , Abelhas , Guanidinas , Humanos , Insetos , Invertebrados , Nitrocompostos , Solo , Tiametoxam , Tiazinas , Tiazóis
17.
Toxicol In Vitro ; 61: 104654, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31533058

RESUMO

A proprietary thiacloprid-based neonicotinoid insecticide formulation is widely used in agriculture to protect vegetables and fruit against various pests. However, its effect on animal cells has not been fully elucidated. In this study, bovine peripheral lymphocytes were incubated with different concentrations of this formulation (10; 30; 60; 120 and 240 µg.mL-1) for 4 h to address the potential cytotoxic and genotoxic effects of the insecticide. Insecticide formulation treatment resulted in decreased cell viability and proliferation, p53-mediated cell cycle arrest at the G0/G1 phase, and apoptosis induction accompanied by elevated levels of mitochondrial superoxide and protein carbonylation. Oxidant-based DNA damage and DNA damage response (DDR) were also observed, namely the formation of micronuclei, DNA double-strand breaks and slightly elevated recruitment of p53 binding protein (53BP1) foci. Our results contribute to the elucidation of insecticide effects on animal lymphocyte cultures after short-term exposure. Due to increased application of neonicotinoids worldwide, resulting in both higher yields and adverse effects on non-target animals and humans, further in vivo and in vitro experiments should be performed to confirm their cytotoxic and genotoxic activities during short-term exposure.


Assuntos
Inseticidas/toxicidade , Linfócitos/efeitos dos fármacos , Neonicotinoides/toxicidade , Tiazinas/toxicidade , Animais , Apoptose/efeitos dos fármacos , Bovinos , Ciclo Celular/efeitos dos fármacos , Células Cultivadas , Dano ao DNA , Instabilidade Genômica , Linfócitos/metabolismo , Estresse Oxidativo/efeitos dos fármacos
18.
Ophthalmic Genet ; 40(4): 350-358, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31496370

RESUMO

Background: Inherited retinal dystrophies are a leading cause of irreversible blindness in children in the United States. Topical carbonic anhydrase inhibitors have improved central vision and cystoid macular edema in patients with retinal dystrophies, but few studies have assessed their efficacy in children. Materials and Methods: A retrospective chart review was performed with Institutional Review Board approval to identify pediatric patients with inherited retinal dystrophies who received topical brinzolamide at a single university center between 2008 and 2015. Serial visual acuity and central macular thicknesses were compared to assess the efficacy of brinzolamide. Results: Seven subjects were identified who met the inclusion criteria. Four had juvenile X-linked retinoschisis, two had retinitis pigmentosa, and one had Leber congenital amaurosis. All were prescribed brinzolamide thrice daily; however, one patient was completely non-compliant. Four of the six treated patients exhibited a mild decrease in central macular thickness in both eyes during the study with all six treated patients having significantly improved vision at the first endpoint, 33.2 ± 8.2 months after treatment initiation. For treated patients, average visual acuity (LogMAR) ± standard error of the mean improved from 0.5 ± 0.04 pre-treatment to 0.3 ± 0.1 at the second endpoint, 50.2 ± 7.3 months after treatment initiation. Conclusions: Mild anatomic improvement of macular cysts was seen in pediatric patients using brinzolamide. Visual acuity improvement occurred even without significant reduction in macular cysts. Further studies are needed to determine whether the beneficial effects of carbonic anhydrase inhibitors are sustained in children with inherited retinal degenerations.


Assuntos
Inibidores da Anidrase Carbônica/uso terapêutico , Edema Macular/tratamento farmacológico , Distrofias Retinianas/tratamento farmacológico , Sulfonamidas/uso terapêutico , Tiazinas/uso terapêutico , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Prognóstico , Estudos Retrospectivos
19.
Ecotoxicol Environ Saf ; 183: 109587, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31509925

RESUMO

Compatibility of neonicotinoid insecticides with the natural enemies has been concerned for decades. This study aims to evaluate and compare the acute and sublethal toxicity effects of neonicotinoid insecticides on three species of Trichogramma parasitoid wasps (i.e. Trichogramma dendrolimi, T. ostriniae and T. confusum) with broad distribution and great relevance to integrated pest management (IPM) strategies. A residual contact bioassay demonstrated that nitenpyram had the greatest intrinsic toxicity to T. dendrolimi and T. ostriniae with LC50 values of 0.060 (0.056-0.065) and 0.066 (0.050-0.087) mg a.i. L-1, respectively. But for T. confusum, the most toxic neonicotinoid insecticide is dinotefuran with a LC50 value of 0.065 (0.055-0.078) mg a.i. L-1. Furthermore, based on the risk quotient estimation, acetamiprid was considered to be the only safe neonicotinoid insecticide (Class 1, RQ<50). A dipped egg contact bioassay showed that neonicotinoid insecticides induced significant toxic effects on the parasitism of three Trichogramma spp. at low-lethal concentrations. Additionally, emergence probability of the unexposed offspring was also significantly reduced by neonicotinoids. According to the estimated EC50 values, acetamiprid possessed the least toxicity to the parasitism and emergence of T. dendrolimi and T. ostriniae, and for T. confusum, the least toxic neonicotinoid insecticide was thiacloprid. Overall, among the test neonicotinoid insecticides, acetamiprid and thiacloprid may exhibit the less ecotoxicity to the test Trichogramma species.


Assuntos
Inseticidas/toxicidade , Neonicotinoides/toxicidade , Vespas/efeitos dos fármacos , Animais , Ecotoxicologia , Guanidinas/toxicidade , Dose Letal Mediana , Nitrocompostos/toxicidade , Tiazinas/toxicidade , Testes de Toxicidade
20.
J Obstet Gynaecol Res ; 45(11): 2228-2236, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31502345

RESUMO

AIM: To identify potential biomarkers for tumor progression and patient outcomes in cervical squamous cell carcinoma. METHODS: We examined the expressions of CK7 and CK17 as potential markers of the squamo-columnar junction, and podoplanin as a basal cell marker using surgical and biopsy samples of patients in grade 3 cervical intraepithelial neoplasia (n = 30), operable invasive carcinoma (OP group, n = 53) and inoperable invasive carcinoma before radiotherapy and/or chemotherapy (RC group, n = 76). RESULTS: The positive rates of CK7 and podoplanin in invasive carcinoma were significantly lower than those in grade 3 cervical intraepithelial neoplasia (P = 0.001, P < 0.0001). The positive rates of CK7 and podoplanin in the RC group were significantly lower than those in the OP group (P < 0.0001, P = 0.04), while CK17 expression showed significantly higher positivity in the RC group than in the OP group (P < 0.0001). Negative CK7 expression showed a potential impact on overall survival in early-stage patients. In the RC group, the prevalence of cases with post-therapeutic residual carcinoma cells was higher in the CK7-negative group than in the positive group (P = 0.003). We found that decreased expression of CK7 could be a prognostic factor in early-stage cervical cancer patients. CONCLUSION: This result may provide strategies and suggestions for new treatment options and follow-up practices in managing patients with cervical cancer.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Neoplasia Intraepitelial Cervical/metabolismo , Queratina-7/metabolismo , Neoplasias do Colo do Útero/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/patologia , Neoplasia Intraepitelial Cervical/patologia , Progressão da Doença , Feminino , Humanos , Iminas/metabolismo , Imuno-Histoquímica , Glicoproteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Tiazinas/metabolismo , Neoplasias do Colo do Útero/patologia
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