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1.
Water Res ; 168: 115139, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31605832

RESUMO

Glyphosate is the most widely-used pesticide for weed control in agriculture and in urban and residential areas. This is the first study to quantify glyphosate and AMPA levels in surface water in Australia from different land uses. Glyphosate and AMPA was measured in surface water from 10 rural streams, 30 urban stormwater wetlands and 9 urban streams located in and around the city of Melbourne, Australia on five occasions between October 2017 and February 2018. Glyphosate and AMPA were present in most of the urban surface water samples. The frequency of detection of glyphosate was 77% in wetlands and 79% in urban streams, whereas it was only detected in 4% of the rural streams. Similarly, AMPA detection was 91% in wetlands and 97% in urban streams, whereas it was only present in 6% of the rural stream samples. In both urban streams and wetlands, the highest average glyphosate concentrations occurred in November (1.8 ±â€¯2.2 µg L-1). Overall, wetlands and streams associated with urban land use are vulnerable to glyphosate contamination. These results highlight the importance of screening for contaminants in urban stormwater to identify the source of pollutants that may end up in aquatic ecosystems and the risks therefrom.


Assuntos
Herbicidas , Poluentes Químicos da Água , Austrália , Cidades , Ecossistema , Monitoramento Ambiental , Glicina/análogos & derivados , Isoxazóis , Rios , Tetrazóis , Áreas Alagadas
2.
Water Res ; 168: 115154, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31630020

RESUMO

Pyrrhotite is often considered as a gangue mineral, and discarded in mine wastes and tailings. Glyphosate and fertilizer, often excessively used in agriculture, flow into water bodies with agriculture runoff, and cause pollution of water bodies. In this study, the pyrrhotite was used as a substrate in a pilot constructed wetland (CW) to remove the glyphosate and nutrients from simulated agriculture runoff. In nearly one year, the pilot pyrrhotite constructed wetland (Pyrr-CW) removed 90.3 ±â€¯6.1% of glyphosate, 88.2 ±â€¯5.1 of total phosphorus (TP) and 60.40 ±â€¯5.60% of total nitrogen (TN) on average, much higher than the control CW. The abundances of sulfur-oxidizing bacteria, such as Sulfurifustis, Sulfuriferula and Thiobacillus, were much higher in the Pyrr-CW than those in the control CW. In the Pyrr-CW goethite was produced by pyrrhotite aerobic oxidation (PAO) and pyrrhotite autotrophic denitrification (PAD) continuously and spontaneously. Higher glyphosate and TP removals were resulted from adsorption on the goethite produced, and higher TN removal was attributed to the PAD. High glyphosate and nutrients removal could keep a long term until the pyrrhotite in the Pyrr-CW was used up. The phosphorus (P) sequestered in the Pyrr-CW existed mainly in organic P, (Fe + Al)P and (Ca + Mg)P, and their order was (Fe + Al)P > organic P > (Ca + Mg)P. No heavy metal ions released from the Pyrr-CW. With higher and lasting removal rate, and lower cost, the Pyrr-CW is a promising technology for simultaneous glyphosate and nutrients removal from agricultural runoff and wastewater.


Assuntos
Nutrientes , Áreas Alagadas , Agricultura , Glicina/análogos & derivados , Nitrogênio , Fósforo , Eliminação de Resíduos Líquidos , Águas Residuárias
3.
Rinsho Ketsueki ; 60(9): 1108-1119, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31597834

RESUMO

Conventional chemotherapy with cytarabine and anthracycline (often referred to as "7+3") has been used for many years in the treatment of acute myeloid leukemia (AML). Despite meaningful advances in areas of supportive care and transplantation, little progress has been made in developing new chemotherapy options. In 2018, The Food and Drug Administration (FDA) of the US approved several novel agents for AML treatment as follows: ivosidenib, an inhibitor of isocitrate dehydrogenase-1; venetoclax, a potent inhibitor of bcl2; and glasdegib, an inhibitor of hedgehog signaling pathway. Moreover, clinical trials of alvocidib (flavopiridol), an inhibitor of the CDK9, pevonedistat, an inhibitor of NEDD8, and APR-246, a reactivator of mutant p53, are in progress. These agents will either be incorporated into the conventional 7+3 regimen or combined with hypomethylating agents to improve the outcome of AML therapy, and the results will guide the next stage of precision medicine in the treatment of AML.


Assuntos
Leucemia Mieloide Aguda/tratamento farmacológico , Benzimidazóis/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Ciclopentanos/farmacologia , Aprovação de Drogas , Flavonoides/farmacologia , Glicina/análogos & derivados , Glicina/uso terapêutico , Humanos , Terapia de Alvo Molecular , Compostos de Fenilureia/uso terapêutico , Piperidinas/farmacologia , Piridinas/uso terapêutico , Pirimidinas/farmacologia , Sulfonamidas/uso terapêutico , Estados Unidos , United States Food and Drug Administration
4.
J Agric Food Chem ; 67(41): 11364-11372, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31542934

RESUMO

The extensive use of pesticide caused an amount of pressure on the environment and increased the potential human health risk. Glyphosate-based herbicide (GBH) is one of the most widely used pesticides based on a 5-enolpyruvylshikimate-3-phosphate synthase target, which does not exist in vertebrates. Here, we study autophagic effects of the most famous commercial GBH Roundup (RDP) on human A549 cells in vitro. Intracellular biochemical assay indicated opening of mitochondrial permeability transition pore, LC3-II conversion, up-regulation of beclin-1, down-regulation of p62, and the changes in the phosphorylation of AMPK and mTOR induced by RDP in A549 cells. Further experimental results indicated that all the effects induced by RDP were related to its adjuvant polyethoxylated tallow amine, not its herbicidal active ingredient glyphosate isopropylamine salt. All these results showed that RDP has the ability to induce AMPK/mTOR-mediated cell autophagy in human A549 cells. This study would provide a theoretical basis for understanding RDP's autophagic effects on human A549 cells and attract attention on the potential human health risks induced by the adjuvant.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Autofagia/efeitos dos fármacos , Glicina/análogos & derivados , Herbicidas/toxicidade , Serina-Treonina Quinases TOR/metabolismo , Células A549 , Proteínas Quinases Ativadas por AMP/genética , Proteína Beclina-1/genética , Proteína Beclina-1/metabolismo , Linhagem Celular , Glicina/toxicidade , Humanos , Serina-Treonina Quinases TOR/genética
5.
Environ Monit Assess ; 191(10): 604, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31485762

RESUMO

The municipality of Limoeiro do Norte-Ceará, located in northeastern Brazil, stands out as a major center of agribusiness due to the high productivity indexes, especially in the irrigated fruit production, with a high consumption of pesticides, including glyphosate, considered potentially carcinogenic by International Agency for Research on Cancer (IARC). In this context, the aim of this study is to evaluate the atmospheric pollution caused by the use of glyphosate herbicide in the rural and urban zones of the municipality of Limoeiro do Norte, evaluating the impacts on the environment and health of the population. Samplings were performed over a period of 4 months using calibrated air samplers. Concentrations of TSP and glyphosate were estimated by gravimetric and liquid chromatography methods, respectively. The results showed TSP levels between 10.8 and 137.4 µg/m3 (mean of 41.1 µg/m3) in rural zone and between 3.87 and 97.7 µg/m3 (average of 38.1 µg/m3) in the urban zone. The glyphosate associated with TSP in the rural zone presented levels between 0.002 and 0.144 µg/m3 (mean of 0.055 µg/m3) and the atmospheric TSP (gas phase) showed levels between 0.313 and 2.939 µg/m3 (average of 1.218 µg/m3). The glyphosate associated with TSP in the urban zone ranged from 0.009 to 2.576 µg/m3 (mean of 1.006 µg/m3). These values can be considered high and dangerous to human health and to the environment.


Assuntos
Poluição do Ar/análise , Monitoramento Ambiental , Glicina/análogos & derivados , Brasil , Poluição Ambiental/análise , Glicina/análise , Herbicidas/análise
6.
Pestic Biochem Physiol ; 159: 22-26, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31400780

RESUMO

Herbicide efficacy depends on herbicides crossing cell and organelle membranes. We evaluated an artificial membrane system to understand how herbicides cross biological membranes. This understanding aids in predicting herbicide behavior in planta and, consequently, efficacy, mode of action, and whether active transporter-based herbicide resistance mechanisms may be possible. Five herbicides with different log Kow and pKa values were assessed: glyphosate, 2,4-D, clopyralid, sulfentrazone and glufosinate. The artificial membrane apparatus included four semipermeable membranes containing buffers with pH 2.7, 5 and/or 7.4, floating in a bath of diethyl ether. These conditions were based on the pH from different cellular compartments and the pKa for these herbicides. Changes in herbicide concentration due to movement were measured using radioactivity or liquid chromatography mass spectrometry. In general, herbicide behavior followed the pattern predicted by their calculated pKa and log Kow. Herbicides added to an acidic phase (pH 2.7) were more mobile than when they were added to the more basic phase (pH 7.4), except when herbicide's pKa was lower than the pH of the starting phase. Clopyralid, 2,4-D, and sulfentrazone showed significant acid trapping behavior due to their weak acid functional groups. Sulfentrazone and 2,4-D had a high affinity for the nonpolar, diethyl ether bath, especially when they were protonated at low pH. Our findings illustrate the robustness of the system to provide predictions about herbicide behavior at the subcellular level.


Assuntos
Herbicidas/metabolismo , Ácido 2,4-Diclorofenoxiacético/metabolismo , Aminobutiratos/metabolismo , Glicina/análogos & derivados , Glicina/metabolismo , Concentração de Íons de Hidrogênio , Membranas Artificiais , Ácidos Picolínicos/metabolismo , Sulfonamidas/metabolismo , Triazóis/metabolismo
7.
J Agric Food Chem ; 67(36): 10010-10017, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31414816

RESUMO

Dominican farmers have started to apply synthetic auxin herbicides (SAHs) as the main alternative to mitigate the impacts of the occurrence of glyphosate-resistant (GR) Parthenium hysterophorus populations in citrus orchards. A GR P. hysterophorus population survived field labeled rates of glyphosate, 2,4-dichlorophenoxyacetic acid (2,4-D), dicamba, and picloram, which showed poor control (<50%). In in vivo assays, resistance levels were high for glyphosate and moderate for picloram, dicamba, and 2,4-D. Sequencing the 5-enolpyruvylshikimate-3-phosphate synthase gene revealed the double Thr-102-Ile and Pro-106-Ser amino acid substitution, conferring resistance to glyphosate. Additionally, reduced absorption and impaired translocation contributed to this resistance. Regarding SAH, impaired 2,4-D transport and enhanced metabolism were confirmed in resistant plants. The application of malathion improved the efficacy of SAHs (control >50%), showing that metabolism of these herbicides was mediated by cytochrome P450 enzymes. This study reports, for the first time, multiple resistance to SAHs and glyphosate in P. hysterophorus.


Assuntos
Asteraceae/efeitos dos fármacos , Citrus/crescimento & desenvolvimento , Glicina/análogos & derivados , Resistência a Herbicidas , Herbicidas/farmacologia , Ácidos Indolacéticos/farmacologia , Ácido 2,4-Diclorofenoxiacético/metabolismo , Ácido 2,4-Diclorofenoxiacético/farmacologia , Asteraceae/metabolismo , Dicamba/metabolismo , Dicamba/farmacologia , Glicina/metabolismo , Glicina/farmacologia , Herbicidas/metabolismo , Ácidos Indolacéticos/metabolismo
8.
J Environ Sci Health B ; 54(7): 539-548, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31264931

RESUMO

Glyphosate (GLP) currently is one of the most widely used herbicides worldwide. The persistence of GLP and its major metabolite, aminomethylphosphonic acid (AMPA) in the environment has been described by other authors. This study was aimed at comparing the GLP and AMPA behavior in sandy and loamy sand soils after spiking with enhanced (445 µg g-1) concentrations of GLP in herbicide KLINIK® (Nufarm, Austria) and bioaugmentation followed by 40 days weathering and a consistent three-stage leaching in a laboratory column experiment. Soil samples were obtained from mineral topsoil (0-10 cm) within former agricultural lands where soil parent material was formed by glacigenic deposits. The total amount of GLP and AMPA collected during three leaching stages was significantly (p<.05) higher from columns with sandy soil, compared to loamy sand soil. Bioaugmentation resulted in considerably lower concentrations of AMPA in leachates, especially in the sets with sandy soil (p=.01). Leachates were tested using FTIR spectroscopy and Daphnia magna. Statistical analysis of the changes in Ntot, Ctot, K+, Mg2+, Al3+, Ca2+, Mn2+ and Fe3+ concentrations in soils after the leaching experiment revealed that the loamy sand soil was likely to be more sensitive to the addition of GLP and bioaugmentation than sandy soil.


Assuntos
Glicina/análogos & derivados , Poluentes do Solo/análise , Solo/química , Agricultura , Animais , Daphnia/efeitos dos fármacos , Glicina/análise , Glicina/química , Glicina/toxicidade , Herbicidas/análise , Herbicidas/química , Isoxazóis/análise , Compostos Organofosforados/análise , Compostos Organofosforados/química , Poluentes do Solo/química , Poluentes do Solo/toxicidade , Espectroscopia de Infravermelho com Transformada de Fourier , Tetrazóis/análise , Testes de Toxicidade
9.
Gan To Kagaku Ryoho ; 46(6): 1043-1047, 2019 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-31273172

RESUMO

Ixazomib, an oral proteasome inhibitor, has been demonstrated to significantly improve progression-free survival(PFS)in patients with relapsed and refractory multiple myeloma(RRMM). Ixazomib has recently been approved in Japan, but its effectiveness and safety have not been fully investigated in a clinical setting. We retrospectively analyzed the records of 28 patients with RRMM who were treated with ixazomib in combination with lenalidomide and dexamethasone(IRd)in our institution between June 2017 and June 2018. The median patient age was 75 years at the start of IRd therapy. In total, 46.4% of the patients had previously received more than 3 treatment lines, prior to this study. The overall response rate was 37.0%, and the median PFS was 286 days. Over a median of 5 cycles of IRd, Grade 3 to 4 leukocytopenia, thrombocytopenia, and anemia occurred in 17.9%, 14.3%, and 32.1% of the patients, respectively; these incidences were higher than in previous reports. The severity of diarrhea or rash, however, was comparable with that in other studies. Patients with an estimated glomerular filtration rate of less than 50mL/min/1.73m2 received a lower cumulative dose of ixazomib and lenalidomide than those with other rates. PFS did not significantly differ between the 2 groups. Although it is necessary to carefully observe IRdtreated patients for hematological toxicity, IRd therapy is effective in heavily pretreated RRMM patients. It might be reasonable to reduce the dose of ixazomib in patients with renal impairment.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mieloma Múltiplo , Compostos de Boro , Dexametasona , Glicina/análogos & derivados , Humanos , Japão , Lenalidomida , Mieloma Múltiplo/tratamento farmacológico , Estudos Retrospectivos
11.
N Engl J Med ; 381(11): 1001-1010, 2019 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-31340089

RESUMO

BACKGROUND: Roxadustat (FG-4592) is an oral inhibitor of hypoxia-inducible factor (HIF) prolyl hydroxylase that stimulates erythropoiesis and regulates iron metabolism. In phase 2 studies involving patients with chronic kidney disease, roxadustat increased levels of endogenous erythropoietin to within or near the physiologic range, along with increasing hemoglobin levels and improving iron homeostasis. Additional data are needed regarding the efficacy and safety of roxadustat for the treatment of anemia in patients with chronic kidney disease who are not undergoing dialysis. METHODS: In this phase 3 trial conducted at 29 sites in China, we randomly assigned 154 patients with chronic kidney disease in a 2:1 ratio to receive roxadustat or placebo three times a week for 8 weeks in a double-blind manner. All the patients had a hemoglobin level of 7.0 to 10.0 g per deciliter at baseline. The randomized phase of the trial was followed by an 18-week open-label period in which all the patients received roxadustat; parenteral iron was withheld. The primary end point was the mean change from baseline in the hemoglobin level, averaged over weeks 7 through 9. RESULTS: During the primary-analysis period, the mean (±SD) change from baseline in the hemoglobin level was an increase of 1.9±1.2 g per deciliter in the roxadustat group and a decrease of 0.4±0.8 g per deciliter in the placebo group (P<0.001). The mean reduction from baseline in the hepcidin level (associated with greater iron availability) was 56.14±63.40 ng per milliliter in the roxadustat group and 15.10±48.06 ng per milliliter in the placebo group. The reduction from baseline in the total cholesterol level was 40.6 mg per deciliter in the roxadustat group and 7.7 mg per deciliter in the placebo group. Hyperkalemia and metabolic acidosis occurred more frequently in the roxadustat group than in the placebo group. The efficacy of roxadustat in hemoglobin correction and maintenance was maintained during the 18-week open-label period. CONCLUSIONS: In Chinese patients with chronic kidney disease who were not undergoing dialysis, those in the roxadustat group had a higher mean hemoglobin level than those in the placebo group after 8 weeks. During the 18-week open-label phase of the trial, roxadustat was associated with continued efficacy. (Funded by FibroGen and FibroGen [China] Medical Technology Development; ClinicalTrials.gov number, NCT02652819.).


Assuntos
Anemia/tratamento farmacológico , Glicina/análogos & derivados , Hemoglobinas/análise , Prolina Dioxigenases do Fator Induzível por Hipóxia/antagonistas & inibidores , Isoquinolinas/uso terapêutico , Insuficiência Renal Crônica/complicações , Acidose/induzido quimicamente , Adulto , Idoso , Anemia/etiologia , Colesterol/sangue , Método Duplo-Cego , Feminino , Glicina/efeitos adversos , Glicina/uso terapêutico , Hematínicos/efeitos adversos , Hematínicos/uso terapêutico , Humanos , Hiperpotassemia/induzido quimicamente , Isoquinolinas/efeitos adversos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/sangue
12.
N Engl J Med ; 381(11): 1011-1022, 2019 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-31340116

RESUMO

BACKGROUND: Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis and regulates iron metabolism. Additional data are needed regarding the effectiveness and safety of roxadustat as compared with standard therapy (epoetin alfa) for the treatment of anemia in patients undergoing dialysis. METHODS: In a trial conducted in China, we randomly assigned (in a 2:1 ratio) patients who had been undergoing dialysis and erythropoiesis-stimulating agent therapy with epoetin alfa for at least 6 weeks to receive roxadustat or epoetin alfa three times per week for 26 weeks. Parenteral iron was withheld except as rescue therapy. The primary end point was the mean change in hemoglobin level from baseline to the average level during weeks 23 through 27. Noninferiority of roxadustat would be established if the lower boundary of the two-sided 95% confidence interval for the difference between the values in the roxadustat group and epoetin alfa group was greater than or equal to -1.0 g per deciliter. Patients in each group had doses adjusted to reach a hemoglobin level of 10.0 to 12.0 g per deciliter. Safety was assessed by analysis of adverse events and clinical laboratory values. RESULTS: A total of 305 patients underwent randomization (204 in the roxadustat group and 101 in the epoetin alfa group), and 256 patients (162 and 94, respectively) completed the 26-week treatment period. The mean baseline hemoglobin level was 10.4 g per deciliter. Roxadustat led to a numerically greater mean (±SD) change in hemoglobin level from baseline to weeks 23 through 27 (0.7±1.1 g per deciliter) than epoetin alfa (0.5±1.0 g per deciliter) and was statistically noninferior (difference, 0.2±1.2 g per deciliter; 95% confidence interval [CI], -0.02 to 0.5). As compared with epoetin alfa, roxadustat increased the transferrin level (difference, 0.43 g per liter; 95% CI, 0.32 to 0.53), maintained the serum iron level (difference, 25 µg per deciliter; 95% CI, 17 to 33), and attenuated decreases in the transferrin saturation (difference, 4.2 percentage points; 95% CI, 1.5 to 6.9). At week 27, the decrease in total cholesterol was greater with roxadustat than with epoetin alfa (difference, -22 mg per deciliter; 95% CI, -29 to -16), as was the decrease in low-density lipoprotein cholesterol (difference, -18 mg per deciliter; 95% CI, -23 to -13). Roxadustat was associated with a mean reduction in hepcidin of 30.2 ng per milliliter (95% CI, -64.8 to -13.6), as compared with 2.3 ng per milliliter (95% CI, -51.6 to 6.2) in the epoetin alfa group. Hyperkalemia and upper respiratory infection occurred at a higher frequency in the roxadustat group, and hypertension occurred at a higher frequency in the epoetin alfa group. CONCLUSIONS: Oral roxadustat was noninferior to parenteral epoetin alfa as therapy for anemia in Chinese patients undergoing dialysis. (Funded by FibroGen and FibroGen [China] Medical Technology Development; ClinicalTrials.gov number, NCT02652806.).


Assuntos
Anemia/tratamento farmacológico , Epoetina alfa/uso terapêutico , Glicina/análogos & derivados , Hematínicos/uso terapêutico , Hemoglobinas/análise , Prolina Dioxigenases do Fator Induzível por Hipóxia/antagonistas & inibidores , Isoquinolinas/uso terapêutico , Insuficiência Renal Crônica/complicações , Adulto , Idoso , Análise de Variância , Anemia/etiologia , Colesterol/sangue , Método Duplo-Cego , Epoetina alfa/efeitos adversos , Feminino , Glicina/efeitos adversos , Glicina/uso terapêutico , Hematínicos/efeitos adversos , Humanos , Hiperpotassemia/induzido quimicamente , Hipertensão/induzido quimicamente , Isoquinolinas/efeitos adversos , Masculino , Pessoa de Meia-Idade , Diálise Renal , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/terapia
13.
Ecotoxicol Environ Saf ; 182: 109400, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31276883

RESUMO

This study was designed to investigate skeletal changes in Podocnemis unifilis embryos derived from artificially incubated eggs exposed to different concentrations of atrazine, glyphosate or atrazine and glyphosate mixture. Forty-two eggs were randomly allocated to one of seven trays containing vermiculite treated distilled water (control group) or the following solutions: 2 or 200 µg L-1 of atrazine (groups A1 and A2 respectively); 65 or 6500 µg L-1 of glyphosate (groups G1 and G2 respectively); 2 µg L-1 and 65 µg L-1 or 200 µg L-1 and 6500 µg L-1 of atrazine and glyphosate mixture (groups AG1 and AG2 respectively). Three eggs per tray were randomly collected on days 30 and 50 of the incubation period. Embryos were submitted to soft tissue diaphanization and stained with Alizarin red S or Alcian blue for morphological analysis of bone and cartilage tissues; histological analysis was performed to confirm ossification changes. Findings were compared between groups. Morphological changes were limited to sclerotic ring features and number of ribs. Malformations rates differed significantly (p < 0.05) between embryos in the control and treated groups A2, AG1 and AG2. Concurrent exposure to atrazine and glyphosate did not affect the presence or severity of embryonic malformations and was not associated with appendicular skeleton changes in P. unifilis embryos. However, further studies focusing on the axial skeleton with particular emphasis on rib abnormalities are warranted.


Assuntos
Atrazina/toxicidade , Glicina/análogos & derivados , Óvulo/efeitos dos fármacos , Praguicidas/toxicidade , Testes de Toxicidade , Animais , Atrazina/análise , Desenvolvimento Ósseo , Osso e Ossos/química , Cartilagem , Ovos , Glicina/toxicidade , Osteogênese , Tartarugas
14.
Medicine (Baltimore) ; 98(30): e16590, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31348300

RESUMO

RATIONALE: Oral ingestion of glyphosate can induce gastrointestinal symptoms such as vomiting, abdominal pain, and hematochezia. Timely and effective treatment of pyloric stenosis caused by glyphosate poisoning is important. PATIENT CONCERNS: The patient had a poor appetite, accompanied by nausea and vomiting of a small amount of dark brown material that resembled blood clots several times a day. Gastroscopy revealed gastric ulcer, a large pyloric antrum ulcer, and a deformed stomach cavity. DIAGNOSIS: Pyloric stenosis due to glyphosate poisoning in a 36-year-old man. INTERVENTIONS: The patients received distal gastrectomy and subsequently transferred to the ICU for further treatment. A mechanical ventilator was used to assist breathing. OUTCOMES: Follow-up was conducted 3 years after surgery. The patient had no problem with food ingestion and experienced no discomfort, such as vomiting, nausea, coughing, or expectoration. LESSONS: Gastrectomy is necessary to treat pyloric stenosis caused by glyphosate poisoning.


Assuntos
Gastrectomia/métodos , Glicina/análogos & derivados , Herbicidas/envenenamento , Estenose Pilórica/induzido quimicamente , Estenose Pilórica/cirurgia , Adulto , Glicina/envenenamento , Humanos , Masculino
15.
Ann Hematol ; 98(9): 2063-2072, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31312928

RESUMO

Rigosertib is a novel multi-kinase inhibitor, which has clinical activity towards leukemic progenitor cells of patients with high-risk myelodysplastic syndromes (MDS) after failure or progression on hypomethylating agents. Since the bone marrow microenvironment plays an important role in MDS pathogenesis, we investigated the impact of rigosertib on cellular compartments within the osteo-hematopoietic niche. Healthy C57BL/6J mice treated with rigosertib for 3 weeks showed a mild suppression of hematopoiesis (hemoglobin and red blood cells, both - 16%, p < 0.01; white blood cells, - 34%, p < 0.05; platelets, - 38%, p < 0.05), whereas there was no difference in the number of hematopoietic stem cells in the bone marrow. Trabecular bone mass of the spine was reduced by rigosertib (- 16%, p = 0.05). This was accompanied by a lower trabecular number and thickness (- 6% and - 10%, respectively, p < 0.05), partly explained by the increase in osteoclast number and surface (p < 0.01). Milder effects of rigosertib on bone mass were detected in an MDS mouse model system (NHD13). However, rigosertib did not further aggravate MDS-associated cytopenia in NHD13 mice. Finally, we tested the effects of rigosertib on human mesenchymal stromal cells (MSC) in vitro and demonstrated reduced cell viability at nanomolar concentrations. Deterioration of the hematopoietic supportive capacity of MDS-MSC after rigosertib pretreatment demonstrated by decreased number of colony-forming units, especially in the monocytic lineage, further supports the idea of disturbed crosstalk within the osteo-hematopoietic niche mediated by rigosertib. Thus, rigosertib exerts inhibitory effects on the stromal components of the osteo-hematopoietic niche which may explain the dissociation between anti-leukemic activity and the absence of hematological improvement.


Assuntos
Glicina/análogos & derivados , Hematopoese/efeitos dos fármacos , Células-Tronco Hematopoéticas , Células-Tronco Mesenquimais , Síndromes Mielodisplásicas , Nicho de Células-Tronco/efeitos dos fármacos , Sulfonas/farmacologia , Animais , Glicina/farmacologia , Células-Tronco Hematopoéticas/metabolismo , Células-Tronco Hematopoéticas/patologia , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/patologia , Camundongos , Camundongos Transgênicos , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/metabolismo , Síndromes Mielodisplásicas/patologia
16.
Artigo em Inglês | MEDLINE | ID: mdl-31287383

RESUMO

A method has been developed for the rapid, specific, accurate, precise and sensitive determination of glufosinate, glyphosate and its major metabolite, aminomethylphosphonic acid, in edible oils, by liquid chromatography coupled to tandem mass spectrometry. Oils were extracted with acidified water (1% formic acid), and the extracts were directly injected into an LC using a Hypercarb column as the stationary phase. The analytes were eluted by a mobile phase of methanol and water containing 1% acetic acid, and they were ionised by electrospray ionisation in negative ion mode. The method was validated and limits of quantification ranged from 5 µg kg-1 (aminomethylphosphonic acid) to 10 µg kg-1 (glyphosate and glufosinate). Three concentrations (10, 50 and 100 µg kg-1) were selected to perform recovery studies. Mean recoveries ranged from 81.4% to 119.4%. Intra and inter-day precision were lower than 19%. Different edible oils were analysed, and no residues of the studied herbicides were detected above limits of quantification.


Assuntos
Aminobutiratos/análise , Análise de Alimentos , Contaminação de Alimentos/análise , Glicina/análogos & derivados , Isoxazóis/análise , Óleos Vegetais/análise , Espectrometria de Massas em Tandem , Tetrazóis/análise , Aminobutiratos/metabolismo , Cromatografia Líquida , Glicina/análise , Glicina/metabolismo , Isoxazóis/metabolismo , Óleos Vegetais/metabolismo , Tetrazóis/metabolismo
17.
Environ Monit Assess ; 191(8): 507, 2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31342281

RESUMO

Glyphosate is the most widespread herbicide and its global use is steadily increasing. Although glyphosate is considered to have low toxicity, its wide application has raised concerns about its effects on human health. The extensive use of glyphosate has risen a need of its continuous monitoring in drinking and surface waters to assure in accordance with the set standards. Within the present study, we have developed a novel assay for the on-site detection of glyphosate by combining flow-through technology with the high specificity of immunorecognition. The proposed biosensing system was based on the detection of fluorescence signal generated by the quantitative replacement of glyphosate in antigen-antibody complex with IgY-type anti-glyphosate antibodies on microbeads by synthetic 5-carboxytetramethylrhodamine (5-TAMRA) conjugated glyphosate. The working range of this assay was in low millimolar range and the time required for glyphosate detection around 0.5 h. The applicability of the immunoassay for glyphosate detection in surface water was tested and the biosensor results were validated with high-performance liquid chromatography.


Assuntos
Técnicas Biossensoriais/métodos , Monitoramento Ambiental/métodos , Glicina/análogos & derivados , Herbicidas/análise , Glicina/análise , Humanos , Imunoensaio , Reprodutibilidade dos Testes , Fatores de Tempo , Poluentes Químicos da Água
18.
Aquat Toxicol ; 214: 105243, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31319294

RESUMO

Glyphosate is one of the most widely used pesticides in the world and can be transported easily by surface runoff, air, and rivers, potentially affecting aquaculture. In this study, the survival rate, intestinal and hepatopancreatic immune and digestive functions, and the intestinal microbial diversity of Chinese mitten crab (Eriocheir sinensis) were evaluated after 7 days of exposure to glyphosate (48.945 mg/L from 1/2 96-h LC50 value). The results showed that glyphosate significantly reduced the survival rate of E. sinensis. After exposure to glyphosate, the totoal antioxidant capacity (T-AOC) in the midgut and hindgut of E. sinensis was significantly decreased, and malondialdehyde (MDA) content in the midgut was significantly increased (P < 0.05). After glyphosate exposure, the activities of digestive enzymes (including lipase and amylase) in the intestinal tract were significantly decreased and trypsin was significantly increased, while three enzymes in the hepatopancreas were significantly increased (P < 0.05). Using high-throughput sequencing analysis of the gut microbiota, the results showed that glyphosate significantly decreased the diversity of E. sinensis gut microbiota, while significantly increasing the taxonomic richness of Bacteroidetes and Proteobacteria (P < 0.05). This study suggested that these bacteria may be involved in glyphosate effects on survival by regulation of immune and digestive function.


Assuntos
Braquiúros/imunologia , Braquiúros/microbiologia , Digestão/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Glicina/análogos & derivados , Herbicidas/toxicidade , Imunidade Inata/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Sequência de Bases , Biodiversidade , Braquiúros/efeitos dos fármacos , Braquiúros/enzimologia , Análise Discriminante , Glicina/toxicidade , Hepatopâncreas/efeitos dos fármacos , Hepatopâncreas/enzimologia , Hepatopâncreas/microbiologia , Intestinos/efeitos dos fármacos , Intestinos/enzimologia , Intestinos/microbiologia , Análise dos Mínimos Quadrados , Filogenia , Análise de Componente Principal , Poluentes Químicos da Água/toxicidade
19.
Ecotoxicol Environ Saf ; 182: 109405, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31276886

RESUMO

The effect of glyphosate, both pure and formulated (Roundup Ultramax®), was evaluated on males of the estuarine crab Neohelice granulata, by means of both in vivo and in vitro assays. The in vivo assays comprised the exposure for 30 d to 1 mg/L of the herbicide, until finally assessing weight gain, levels of energy reserves, sperm number per spermatophore, proportion of abnormal spermatophores, and sperm viability. At the end of this assay, significant (p < 0.05) decrease in weight gain and muscle protein levels was detected by effect of both pure and formulated glyphosate. In spermatophores from the vas deferens, a significant (p < 0.05) decrease of the sperm count was observed by effect of Roundup, while a significant incidence (p < 0.05) of abnormal spermatophores was observed either with glyphosate or with Roundup treatment. No changes were seen in the spermatophore area or in vas deferens secretions. Since no sperm mortality was induced by the formulated herbicide, we propose a probable inhibiting effect on spermatogenesis might explain the observed sperm count decrease. In this sense, an in vitro assay was designed by incubating testes and vasa deferentia with Roundup, in order to corroborate the possible interference of glyphosate with the secretion of the androgenic gland hormone that controls the spermatogenesis, in the presence or absence of the androgenic gland. Although the herbicide per se was able to reduce the sperm count to some extent, the increase in the number of spermatozoa/spermatophore produced by the co-incubation with the androgenic gland was completely reverted by the addition of Roundup (1 mg/L of glyphosate a.e.), suggesting that an inhibition on the secretion and/or transduction of the androgenic gland hormone could be taking place.


Assuntos
Braquiúros/efeitos dos fármacos , Glicina/análogos & derivados , Herbicidas/toxicidade , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Androgênios/metabolismo , Animais , Estuários , Glicina/toxicidade , Masculino , Contagem de Espermatozoides , Espermatogênese/efeitos dos fármacos
20.
Chemosphere ; 233: 905-912, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31340418

RESUMO

We investigated the interconnected roles of reactive oxygen species (ROS) generated upon seed exposure to glyphosate and/or gibberellic acid (GA3), and the possible interaction between the herbicide and the plant hormone during germination of sorghum seeds. GA3 decreased antioxidant enzyme activity in embryos, and the over accumulation of hydrogen peroxide (H2O2) in 1000 mM GA3-treated seeds resulted in the lowest germinability among treatments. The deleterious effects of glyphosate on germination rate, in contrast, were not related to H2O2 accumulation, but to its interference with the mitochondrial electron transport chain. However, interactions among glyphosate, GA3 and H2O2 during seed germination were observed. Similar to paclobutrazol, glyphosate appears to interfere with the de novo synthesis of gibberellin, which modulates seed germination through oxidative metabolism. Seeds experiencing increased oxidative status due to GA3 (100 mM) or H2O2 (50 mM) applications had the effects of glyphosate on germination rate reversed. Since decreased ATP synthesis is a secondary effect of glyphosate, increased H2O2 concentrations in embryos must facilitate germination by decreasing the energy required by ATP-demanding metabolism. Our results showed that glyphosate affect seed germination of sorghum, and that the herbicide interacts with oxidative and gibberellin metabolisms.


Assuntos
Germinação/efeitos dos fármacos , Giberelinas/metabolismo , Glicina/análogos & derivados , Herbicidas/farmacologia , Peróxido de Hidrogênio/metabolismo , Reguladores de Crescimento de Planta/metabolismo , Sorghum/metabolismo , Antioxidantes/metabolismo , Grão Comestível/metabolismo , Transporte de Elétrons/efeitos dos fármacos , Glicina/farmacologia , Sementes/efeitos dos fármacos
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