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1.
Chem Pharm Bull (Tokyo) ; 72(3): 336-339, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38522900

RESUMO

This study showcases the 1,2-migration reactions of alkyl and aryl groups on the indole molecule. Trifluoromethanesulfonic acid effectively facilitates the migration of the substituent from C3- to C2-position of the indole structure. The resulting C2-substituted indoles offer a valuable pathway for the synthesis of natural products and medicinal compounds.


Assuntos
Produtos Biológicos , Indóis , Indóis/química , Mesilatos
2.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(1): 14-19, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38387893

RESUMO

OBJECTIVE: To explore the clinical efficacy and safety of flumatinib mesylate produced in China in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP). METHODS: 32 newly diagnosed CML-CP patients admitted to the Hematology Department of the Affiliated Hospital of Southwest Medical University from March 1, 2020 to March 31, 2022, who had never received any tyrosine kinase inhibitor (TKI) were included in the study. The patients were treated by flumatinib mesylate 600mg once daily. The hematologic, cytogenetic and molecular responses were assessed at 3-, 6- and 12-month, and adverse effects of the drug were evaluated. RESULTS: 31 patients were treated with flumatinib for≥3 months, of which 24 patients were treated for ≥6 months and 14 patients were treated for≥12 months. At 3rd month of treatment, 30 out of 31 patients achieved complete hematologic response (CHR); 24 patients underwent cytogenetic testing and 22 cases achieved major cytogenetic response(MCyR), of which 21 cases achieved complete cytogenetic response (CCyR); Among 25 patients who underwent molecular testing, 22 patients had BCR-ABLIS≤10%, including 10 patients with BCR-ABLIS≤0.1%, and 6 patients with BCR-ABLIS≤0.01%. At 6th month of treatment, 23 out of 24 patients achieved CHR; 17 patients underwent cytogenetic testing and all achieved CCyR; Among 23 patients who underwent molecular testing, 20 patients had BCR-ABLIS≤1%, including 16 patients with BCR-ABLIS≤0.1% and 12 patients with BCR-ABLIS≤0.01%. At 12nd month of treatment, all 14 patients achieved CHR and CCyR; Among them, 10 patients had BCR-ABLIS≤0.1%, including 9 patients with BCR-ABLIS≤0.01%. The grade Ⅲ/Ⅳ leukopenia, thrombocytopenia and anemia rates in the patients were 13.3%, 20.0% and 3.3%, respectively. One patient stopped flumatinib therapy due to severe and persistent hematologic toxicity. The major non-hematologic adverse events were abnormal liver function (20%), diarrhea (10%), bone/joint pain (10%), muscle spasm (10%), rash (6.7%), acute kidney injury (6.7%) and nausea(3.3%), most of which were grade I-II. No patient experienced grade Ⅳ non-hematologic adverse events. No drug toxicity-related death occurred. CONCLUSION: Flumatinib mesglate, as the first-line treatment for newly diagnosed CML-CP, can enable the patients to achieve early and deep molecular and cytogenetic responses, and shows good safety.


Assuntos
Anemia , Antineoplásicos , Leucemia Mielogênica Crônica BCR-ABL Positiva , Trombocitopenia , Humanos , Mesilato de Imatinib/uso terapêutico , Pirimidinas/farmacologia , Proteínas de Fusão bcr-abl , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Benzamidas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Resultado do Tratamento , Mesilatos/uso terapêutico , Antineoplásicos/uso terapêutico
3.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(1): 14-19, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38387894

RESUMO

OBJECTIVE: To evaluate the efficacy and safty of China-made flumatinib mesylate in the treatment of chronic myeloid leukemia in chronic phase (CML-CP). METHODS: 42 CML-CP patients treated with Chinese produced flumatinib (oral, 600 mg, 1/d) were included in the study, including 14 newly diagnosed patients and 28 patients underwent conversion therapy. The hematological, cytogenetic and molecular response and safety were observed and evaluated after 3, 6 and 12 months of treatment. RESULTS: 35 patients were treated for more than 3 months, among which 31 patients were treated for more than 6 months and 17 patients were treated for more than 12 months. After 3 months of treatment, 33 patients underwent hematological, cytogenetic and molecular examination. Of these, 32 patients achieved complete hematological response (CHR), 13 patients achieved complete cytogenetic response (CCyR), 20 patients showed BCR-ABLIS≤10% and 7 patients reached major molecular response (MMR). After 6 months of treatment, all 30 patients who could evaluate efficacy achieved CHR, of which 17 patients achieved CCyR, 18 patients showed BCR-ABLIS≤1% and 16 patients reached MMR. After 12 months of treatment, all 17 patients were evaluated for efficacy, all achieved CHR, 10 patients obtained CCyR, 7 patients reached MMR. Grade III or IV thrombocytopenia, leukopenia and anemia occurred in 7, 2 and 1 patients, respectively. The non-hematological adverse reactions were diarrhea in 6 cases, renal function damage in 4 cases, rash and pruritus in 3 cases, liver function damage in 3 cases, nausea in 1 case, fever in 1 case, bone/joint or muscle pain in 1 case. CONCLUSION: In the real world, China-made flumatinib mesylate has a positive short-term efficacy and reliable safety in the treatment of CML-CP patients, whether as first-line treatment or second- and third-line conversion therapy.


Assuntos
Anemia , Antineoplásicos , Leucemia Mielogênica Crônica BCR-ABL Positiva , Trombocitopenia , Humanos , Mesilato de Imatinib/uso terapêutico , Resultado do Tratamento , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , China , Mesilatos/uso terapêutico , Antineoplásicos/uso terapêutico , Proteínas de Fusão bcr-abl/genética
4.
Headache ; 64(3): 266-275, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38413540

RESUMO

OBJECTIVE: To compare the safety and pharmacokinetics (PK) of dihydroergotamine (DHE) after administration of intranasal DHE powder (STS101), liquid nasal spray (LNS) DHE mesylate, and intramuscular (IM) DHE mesylate injection in healthy participants. BACKGROUND: DHE is an effective acute migraine treatment; however, self-administration difficulties have prevented its broader role in the management of migraine. METHODS: This randomized, active-controlled, five-period crossover study was conducted over 5 weeks separated by 1-week washout periods. Three STS101 dosage strengths (5.2, 7.0, 8.6 mg), and one dose each of LNS DHE 2.0 mg, and IM DHE 1.0 mg, were administered to 36 healthy participants. Liquid chromatography, tandem mass spectrometry was used to determine DHE (including its 8'OH-DHE metabolite) plasma levels and to calculate PK parameters (Cmax , Tmax , AUC0-2h , AUC0-last , AUC0-inf , and t1/2 ). Safety was evaluated by monitoring adverse events (AEs), vital signs, electrocardiograms, nasal examinations, and laboratory parameters. RESULTS: Thirty-six participants (mean age 36 years; 19% Hispanic Black and 81% Hispanic White) were enrolled. DHE plasma concentrations rose rapidly after STS101 5.2, 7.0, and 8.6 mg and IM DHE injection, with mean concentrations greater than 2000 pg/mL for all STS101 dose strengths at 20 min. All STS101 dose strengths showed approximately 3-fold higher Cmax , AUC0-2h , and AUC0-inf , than the LNS DHE. The mean AUC0-inf of STS101 7.0 and 8.6 mg were comparable to IM DHE (12,600 and 13,200 vs. 13,400 h × pg/mL). All STS101 dose strengths showed substantially lower variability (CV%) compared to LNS DHE for Cmax (35%-41% vs. 87%), and AUC0-inf (37%-46% vs. 65%). STS101 was well tolerated, and all treatment-emergent AEs were mild and transient. CONCLUSION: STS101 showed rapid absorption and was well tolerated with mild and transient treatment-emergent AEs. Achieving effective DHE plasma concentrations within 10 min, STS101 displayed a favorable PK profile relative to the LNS with higher Cmax , AUC0-2h , and AUC0inf , and with greater response consistency. The AUC0-inf was comparable to IM DHE.


Assuntos
Di-Hidroergotamina , Transtornos de Enxaqueca , Adulto , Humanos , Sprays Nasais , Estudos Cross-Over , Pós/uso terapêutico , Transtornos de Enxaqueca/tratamento farmacológico , Mesilatos/uso terapêutico
5.
Waste Manag ; 178: 105-114, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38387254

RESUMO

With the vigorous development of the new energy industry, the use of lithium-ion batteries (LIBs) is growing exponentially, and the recycling of spent LIBs has gradually become a research hotspot. Currently, recycling both cathode and anode materials of LIBs is important to environmental protection and resource recycling. This research reportsa method ofefficient purification and high-quality regeneration of graphite from spent LIBs by surfactant-assisted methanesulfonic acid (MSA). Under the optimal conditions (0.006 mol/L sodium dodecyl sulfonate, 0.25 mol/L MSA, 10 vol% hydrogen peroxide, liquid-solid ratio of 30:1 mL/g, 60 °C, 1.5 h), the purity of the regenerated graphite was 99.7 %, and the recovery efficiency was 98.0 %. The regenerated graphite showed the characteristics of small interplanar spacing, high degree of graphitization, a small number of surface defects, and excellent pore structure, which was closer to commercial graphite. Furthermore, the regenerated graphite electrode exhibited superior rate performance and cycling stability with a high specific capacity of 397.03 mAh/g after 50 cycles at 0.1C and a charge-discharge efficiency of 99.33 %. The recovery of anode graphite beneficial for resource utilization, environmental protection, and cost control throughout the entire production chain.


Assuntos
Grafite , Lítio , Mesilatos , Lítio/química , Tensoativos , Reciclagem
6.
Ecotoxicol Environ Saf ; 273: 116144, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38412630

RESUMO

Mesotrione, topramezone, tembotrione, and sulcotrione are four types of 4-hydroxyphenylpyruvate dioxidase (HPPD) inhibitor herbicides that are extensively employed in agricultural practices, but their usage also leads to environmental pollution and poses risks to human health. A probe (E)-1-((2-(pyridin-2-yl) hydrazineylidene) methyl) naphthalen-2-ol (CHMN) based on chelation enhancement (CHEF) effect synthesized. CHMN was first chelated with Zn2+ to form a probe system with green, which can be further used to detect mesotrione, topramezone, tembotrione and sulcotrione in complicated environment. CHMN-Zn2+ detection of four pesticides was accurate, with an excellent linear relationship between 0 and 100 µM. The detection limits were LODmesotrione = 7.79 µM, LODtopramezone = 1.91 µM, LODtembotrione = 1.38 µM and LODsulcotrione = 2.43 µM. The detection time is 1 min, and it is successfully applied in real water sample and bioimaging. This work can provide a novel method for studying the migration and behavior of environmental pollutants.


Assuntos
4-Hidroxifenilpiruvato Dioxigenase , Cicloexanonas , Herbicidas , Mesilatos , Sulfonas , Humanos , Fluorescência , Herbicidas/farmacologia , Zinco , Inibidores Enzimáticos/farmacologia
7.
Artigo em Inglês | MEDLINE | ID: mdl-38373513

RESUMO

The effect of anesthesia/euthanasia with ethyl 3-aminobenzoate methanesulfonate (MS-222) on the oxidative status of Hyla arborea tadpoles was examined to determine whether the use of the anesthetic can confound the experimental results of the oxidative stress-based investigation. The experiment was conducted on two groups of tadpoles reared at different temperatures to produce differences in antioxidant capacity between the groups. After development at different temperatures (20 °C and 25 °C), the animals were exposed to different concentrations of MS-222 (0, 0.1, 1, and 5 g/L) for 15 min. The higher temperature decreased catalase activity, glutathione and protein carbonyl levels and increased glutathione reductase activity. The glutathione level and glutathione/thiol-related parameters were significantly changed after MS-222 exposure. However, individuals from the different temperature groups responded differently to the tested anesthetic, pointing to the possible influence of the initial levels of antioxidant capacity. The analysis of the interaction between the factors (temperature and MS-222) confirmed that the anesthetic can confound the results regarding the effects of temperature on the oxidative status parameters. The concentration of 0.1 g/L MS-222 had the lowest influence on the alterations in oxidative status and the results of the effect of temperature. A brief review of the current literature on the use of MS-222 in tadpoles made clear the absence of precise information on anesthetic concentration and exposure time. Similar studies should be repeated and extended to other amphibian species and other factors of interest to provide better guidance on tadpole anesthesia/euthanasia for future experiments that consider oxidative status parameters.


Assuntos
Aminobenzoatos , Anestésicos , Antioxidantes , Humanos , Animais , Anestésicos/toxicidade , Ésteres , Glutationa , Mesilatos , Estresse Oxidativo
8.
Neuropharmacology ; 248: 109863, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38325771

RESUMO

Tremendous progress has been made to develop the therapy of Alzheimer's disease (AD). Existing several anti-AD remedies, with certain limitations, are far from adequate. Evidence suggests that dihydroergocristine (DHEC) mesylate, one of the main components of Ergoloid mesylates, can reduce the production of amyloid-ß in vitro. However, the therapeutic effect of DHEC mesylate in AD and its underlying mechanism are still largely unknown. Herein, we characterized the pharmacological effect of DHEC mesylate in AD and found that the spatial memory disorders and Alzheimer-type pathologies were alleviated by DHEC mesylate administration. Moreover, we demonstrated that DHEC mesylate improved aberrant bisecting N-glycosylation, which was identified as a potential biomarker of AD. We further explored the underlying mechanism and confirmed that DHEC mesylate protected against AD via AMPK and ERK signaling, in which, AMPK was the dominant down-stream molecule of DHEC mesylate. In summary, our findings provide foundations for development of DHEC mesylate as a therapeutic approach for AD.


Assuntos
Doença de Alzheimer , Humanos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/patologia , Di-Hidroergocristina , Glicosilação , Proteínas Quinases Ativadas por AMP , Peptídeos beta-Amiloides/metabolismo , Mesilatos/uso terapêutico , Proteínas tau
9.
Mol Cancer ; 23(1): 12, 2024 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-38200517

RESUMO

BACKGROUND: Malignant peritoneal mesothelioma (MPM) is an extremely rare and highly invasive tumor. Due to the lack of accurate models that reflect the biological characteristics of primary tumors, studying MPM remains challenging and is associated with an exceedingly unfavorable prognosis. This study was aimed to establish a new potential preclinical model for MPM using patient-derived MPM organoids (MPMOs) and to comprehensively evaluate the practicality of this model in medical research and its feasibility in guiding individualized patient treatment. METHODS: MPMOs were constructed using tumor tissue from MPM patients. Histopathological analysis and whole genome sequencing (WGS) were employed to determine the ability of MPMOs to replicate the original tumor's genetic and histological characteristics. The subcutaneous and orthotopic xenograft models were employed to assess the feasibility of establishing an in vivo model of MPM. MPMOs were also used to conduct drug screening and compare the results with retrospective analysis of patients after treatment, in order to evaluate the potential of MPMOs in predicting the effectiveness of drugs in MPM patients. RESULTS: We successfully established a culture method for human MPM organoids using tumor tissue from MPM patients and provided a comprehensive description of the necessary medium components for MPMOs. Pathological examination and WGS revealed that MPMOs accurately represented the histological characteristics and genomic heterogeneity of the original tumors. In terms of application, the success rate of creating subcutaneous and orthotopic xenograft models using MPMOs was 88% and 100% respectively. Drug sensitivity assays demonstrated that MPMOs have different medication responses, and these differences were compatible with the real situation of the patients. CONCLUSION: This study presents a method for generating human MPM organoids, which can serve as a valuable research tool and contribute to the advancement of MPM research. Additionally, these organoids can be utilized as a means to evaluate the effectiveness of drug treatments for MPM patients, offering a model for personalized treatment approaches.


Assuntos
Mesotelioma Maligno , Mesilatos , Neoplasias Peritoneais , Piperidinas , Humanos , Animais , Estudos Retrospectivos , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/genética , Modelos Animais de Doenças , Organoides
10.
J Zoo Wildl Med ; 54(4): 825-829, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38252008

RESUMO

Little research has taken place on the effect of euthanasia methods on biophysical and biochemical changes at the time of euthanasia in fish. These changes are used in multiple species to determine stress levels before death. Koi (Cyprinus carpio) are an important fish species often used in laboratory research, kept in backyard ponds, and managed in zoological and aquarium collections. The current study evaluated euthanasia of koi by immersion in 0.5 g/L tricaine methanesulfonate (MS-222) (n = 10), 0.5 g/L clove oil (n = 8), 1 g/L clove oil (n = 10), and CO2 (n = 7) on time to cessation of opercular movement, plasma lactate levels, and plasma cortisol levels. CO2 had the longest mean time to cessation of opercular movement, and MS-222 had the shortest (mean CO2: 24.9 min, range 13.18-31.35 min; MS-222: 2.68 min, range 1.33-4.5 min). The difference was not significant between any of the groups for plasma cortisol or lactate levels. MS-222 demonstrated the highest cortisol levels, and CO2 had the lowest (mean CO2: 108.7 ng/ml, range 33.9-195.8 ng/ml; MS-222: 650.6 ng/ml, range 77.3-2374.9 ng/ml). Average lactate levels were highest for 1 g/L clove oil and lowest for 0.5 g/L clove oil (mean 0.5 g/L clove oil: 5.1 mmol/L, range 1.8-8.1 mmol/L; 1 g/L clove oil: 7.4 mmol/L, range 5.6-10.5 mmol/L).


Assuntos
Aminobenzoatos , Carpas , Ácido Láctico , Animais , Dióxido de Carbono , Óleo de Cravo/farmacologia , Hidrocortisona , Água , Imersão , Anestésicos Locais , Ésteres , Mesilatos
11.
Int J Biol Macromol ; 256(Pt 2): 128445, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38029916

RESUMO

Preparation of reusable protic ionic liquid, triflic acid-immobilized aminoethyl piperazine-modified pectin (Pec-AEP-TfOH), with excellent activity and selectivity in modified Schmidt synthesis of nitriles from aldehydes and Si(CH3)3N3 has been described. The structure of the catalyst was characterized using FT-IR, XRD, FE-SEM, EDX-mapping, and TGA-DTA. The reaction demonstrated a broad substrate scope for a variety of benzaldehyde derivatives with electron withdrawing/donating substituents and heterocyclic aldehydes with yields between 85 and 96 % at room temperature. Also, the Pec-AEP-TfOH showed an excellent selectivity for the nitriles in which no formanilide was obtained. Furthermore, the Pec-AEP-TfOH revealed a remarkable chemoselectivity for aldehydes in the presence of acids or ketones. It is worth noting that TfOH as a precious superacid was immobilized for the first time in the selective Schmidt synthesis of nitriles to improve the eco-friendliness and economic efficiency of the process. Furthermore, the catalyst was cost-effective, metal-free, safe, scalable, and reusable (5 times) and its heterogeneity was confirmed by hot-filtration test.


Assuntos
Líquidos Iônicos , Mesilatos , Líquidos Iônicos/química , Nitrilas/química , Pectinas , Espectroscopia de Infravermelho com Transformada de Fourier , Aldeídos/química , Piperazinas
12.
J Environ Manage ; 351: 119795, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38091735

RESUMO

A carbon trading market (CTM) policy for trading carbon dioxide emission rights as a commodity was created to reduce greenhouse gas emissions. CTMs operate differently in different countries and regions, and their interactions deserve an in-depth study. This study focused on the world's largest CTM, the European Union (EU), and the CTM of China, largest carbon-emitting country. First, we evaluate the liquidity and volatility of the two CTMs. Subsequently, the VAR model is used to explore the mean spillover effect between the two markets and the BEKK-GARCH model is used to explore the volatility spillover effect between the two markets. The study concludes that: (1) The liquidity of China's CTM is better than that of the EU's CTM. (2) Both the EU and Chinese CTMs are unstable, but the volatility of the Chinese CTM is lower than that of the EU CTM. (3) Price changes in the EU and Hubei CTMs have a mutual influence. (4) There are interactions between the market fluctuations of the EU CTM and the Shanghai CTM and those of the EU CTM and the Hubei CTM. The results of this study have implications for the construction and development of CTMs in the EU and China.


Assuntos
Cicloexanos , Mesilatos , China , União Europeia
13.
Environ Pollut ; 343: 123183, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38110047

RESUMO

With the gradual deepening of the research and governance of air pollution, chemical transport models (CTMs), especially the third-generation CTMs based on the "1 atm" theory, have been recognized as important tools for atmospheric environment research and air quality management. In this review article, we screened 2396 peer-reviewed manuscripts on the application of four pre-selected regional CTMs in the past five years. CAMx, CMAQ, WRF-Chem and NAQPMS models are well used in the simulation of atmospheric pollutants. In the simulation study of secondary pollutants such as O3, secondary organic aerosol (SOA), sulfates, nitrates, and ammonium (SNA), the CMAQ model has been widely applied. Secondly, model evaluation indicators are diverse, and the establishment of evaluation criteria has gone through the long-term efforts of predecessors. However, the model performance evaluation system still needs further specification. Furthermore, temporal-spatial resolution, emission inventory, meteorological field and atmospheric chemical mechanism are the main sources of uncertainty, and have certain interference with the simulation results. Among them, the inventory and mechanism are particularly important, and are also the top priorities in future simulation research.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Cicloexanos , Mesilatos , Poluentes Atmosféricos/análise , Material Particulado/análise , Incerteza , Poluição do Ar/análise , Monitoramento Ambiental/métodos
14.
Environ Sci Technol ; 58(1): 649-659, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38131199

RESUMO

Iodine oxoacids (HIO3 and HIO2)-driven nucleation has been suggested to efficiently contribute to new particle formation (NPF) in marine atmospheres. Abundant atmospheric nucleation precursors may further enhance HIO3-HIO2-driven nucleation through various multicomponent nucleation mechanisms. However, the specific enhancing potential (EP) of different precursors remains largely unknown. Herein, the EP-based screening model of precursors and enhancing mechanism of the precursor with the highest EP on HIO3-HIO2 nucleation were investigated. The formation free energies (ΔG), as critical parameters for evaluating EP, were calculated for the dimers of 63 selected precursors with HIO2. Based on the ΔG values, (1) a quantitative structure-activity relationship model was developed for evaluating ΔG of other precursors and (2) atmospheric concentrations of 63 (precursor)1(HIO2)1 dimer clusters were assessed to identify the precursors with the highest EP for HIO3-HIO2-driven nucleation by combining with earlier results for the nucleation with HIO3 as the partner. Methanesulfonic acid (MSA) was found to be one of the precursors with the highest EP. Finally, we found that MSA can effectively enhance HIO3-HIO2 nucleation at atmospheric conditions by studying larger MSA-HIO3-HIO2 clusters. These results augment our current understanding of HIO3-HIO2 and MSA-driven nucleation and may suggest a larger impact of HIO2 in atmospheric aerosol nucleation.


Assuntos
Atmosfera , Clima , Mesilatos
15.
Ecotoxicol Environ Saf ; 270: 115870, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38159340

RESUMO

Chiral pesticides that are still commercialized and incorporated into the environment as racemic mixtures of enantiomers require evaluation of the enantioselectivity of their biological activity and environmental fate processes for a better prediction of their field efficacy and environmental risks. In this work, we successfully separated the enantiomers of the chiral herbicide ethofumesate (ETFM), determined their absolute configuration, and characterized their herbicidal activity as well as their adsorption, degradation, enantiomerization, and leaching in Mediterranean agricultural soils. While the herbicidal activity of R-ethofumesate to the sensitive species Portulaca grandiflora was greater than that of S-ethofumesate, the adsorption, degradation, and leaching of the herbicide showed negligible enantioselectivity and enantiomer interconversion did not occur in soils. The adsorption of both enantiomers showed a positive correlation with the soil organic carbon content (r = 0.856, P = 0.015), and their degradation in soils occurred slowly (DT50 > 60 days) and at similar rates independent of their application as individual enantiomers or as a racemic mixture of enantiomers. The addition of three highly adsorptive materials to a scarcely adsorptive soil increased the adsorption of the enantiomers of ETFM and delayed their degradation without affecting the non-enantioselective character of the processes. As a result of their high adsorption capacity, the materials were highly effective in reducing the leaching of both enantiomers of ETFM through soil columns. The results of this work indicate that the application of single-enantiomer ETFM formulations, based on a higher herbicidal activity or a lower toxicity to non-target organisms of the formulated enantiomer, would reduce considerable exposure risks associated with incorporating into the environment the less favorable enantiomer, as this would show long persistence and high leaching potential in soils similar to its optical isomer.


Assuntos
Benzofuranos , Carvão Vegetal , Fungicidas Industriais , Herbicidas , Mesilatos , Poluentes do Solo , Solo , Estereoisomerismo , Carbono , Fungicidas Industriais/metabolismo , Poluentes do Solo/metabolismo , Alanina/metabolismo , Biodegradação Ambiental
16.
ACS Sens ; 8(12): 4707-4715, 2023 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-38064687

RESUMO

Hyperpolarized (HP) xenon-129 (129Xe) magnetic resonance imaging (MRI) has the potential to be used as a molecular imaging modality. For this purpose, numerous supramolecular cages have been developed and evaluated in the past. Herein, we report a novel and unique macrocycle that can be successfully utilized for xenon MRI, the resorcinarene trimer methanesulfonate (R3-Noria-MeSO3H). This molecule is capable of two different contrast mechanisms for xenon-MRI, resulting from an increase in the effective spin-spin relaxation and hyperpolarized chemical exchange saturation transfer (HyperCEST). We have demonstrated a superior negative contrast caused by R3-Noria-MeSO3H on HP 129Xe MRI at 3.0 T as well as HyperCEST imaging of the studied macrocycle. Additionally, we have found that the complex aggregation behaviors of R3-Noria-methanesulfonate and its impact on xenon-129 relaxivity are an area for future study.


Assuntos
Imageamento por Ressonância Magnética , Isótopos de Xenônio , Imageamento por Ressonância Magnética/métodos , Isótopos de Xenônio/química , Xenônio/química , Meios de Contraste/química , Mesilatos
17.
Arch Razi Inst ; 78(3): 1023-1028, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-38028832

RESUMO

Rasagiline is a selective and irreversible inhibitor of monoamine oxidase B (MAO-B) that is effective in the treatment of Parkinson's disease (PD). It had antioxidant and anti-apoptotic activity in experimental models. Moreover, it has low permeability and its oral bioavailability is weak and highly variable due to extensive first-pass hepatic metabolism (35%). This study aimed to formulate rasagiline mesylate (RM) as a lipid-polymer hybrid nanoparticle in order to enhance its permeation and increase its chance to be absorbed by lymphatic circulation to avoid metabolism and control its release. Successful formulation (PCL-2) was reached by the nanoprecipitation method using polycaprolactone with RM in the organic phase and lecithin in the aqueous phase DSPE-PEG. The lipid:polymer ratio of 24% and DSPE: lecithin of 50% resulted in stable nanoparticles having a particle size of 132±4.58 nm, polydispersity index of 0.273±0.02, zeta potential of -25.6±3.3, entrapment efficiency of 46±3.9%, and drug loading of 51.93±6.5. Results showed that the diffusion was more effective on the release profile than the degradation and resulted in a Fickian diffusion mechanism.


Assuntos
Inibidores da Monoaminoxidase , Fármacos Neuroprotetores , Animais , Inibidores da Monoaminoxidase/farmacologia , Inibidores da Monoaminoxidase/uso terapêutico , Lecitinas , Fármacos Neuroprotetores/farmacologia , Mesilatos
18.
Sci Rep ; 13(1): 18348, 2023 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-37884605

RESUMO

The single-component colistin E2, with superior antibacterial activity and lower toxicity, was being developed as the latest generation of polymyxin drugs. However, colistin E2 has not been tested quantitatively in biological matrices. In this study, based on the quantitative detection of colistin methanesulphonate (CMS) and colistin by Zhao et al., 15N-labeled colistin E2 was used as an internal standard (IS) for a more accurate quantitative detection of CMS E2 in human plasma. A rapid ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) assay method was developed for determination of CMS E2 and colistin E2 in human plasma. After pretreatment of plasma samples by 96-well SPE Supra-Clean Weak Cation Exchange (WCX) plate, the formed colistin E2 was detected and quantified by UHPLC-MS/MS system. All plasma lots were found to be free of interferences with the analyte. The matrix has no effect on the quantitation of the analyte. No significant effect of the carryover was observed. The dilution integrity was demonstrated in plasma samples without the loss of accuracy and precision. The lower limit of quantification (LLOQ) was 0.0300 mg/L for colistin E2 in plasma with accuracy (relative error, 5.1-12.7%) and precision (relative standard deviation, - 5.7-9.3%). Stability of CMS E2 and colistin E2 was demonstrated in biological samples before and during sample treatment, and in the extract. Furthermore, this method was successfully applied to the analysis of plasma samples obtained from Chinese healthy volunteers receiving a single intravenous CMS E2 dose of 5 mg/kg. In conclusion, the detection method was characterized by speed and high accuracy, which laid a solid foundation for the subsequent development of CMS E2 drug.


Assuntos
Colistina , Espectrometria de Massas em Tandem , Humanos , Colistina/química , Espectrometria de Massas em Tandem/métodos , Antibacterianos/química , Cromatografia Líquida de Alta Pressão/métodos , Mesilatos
19.
IEEE Trans Biomed Eng ; 70(9): 2564-2572, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37656637

RESUMO

BACKGROUND: Neurons demonstrate very distinct nonlinear activation dynamics, influenced by the neuron type, morphology, ion channel expression, and various other factors. The measurement of the activation dynamics can identify the neural target of stimulation and detect deviations, e.g., for diagnosis. This paper describes a tool for closed-loop sequential parameter estimation (SPE) of the activation dynamics through transcranial magnetic stimulation (TMS). The proposed SPE method operates in real time, selects ideal stimulus parameters, detects and processes the response, and concurrently estimates the input-output (IO) curve and the first-order approximation of the activated neural target. OBJECTIVE: To develop a method for concurrent SPE of the first-order activation dynamics and IO curve with closed-loop TMS. METHOD: First, identifiability of an integrated model of the first-order neural activation dynamics and IO curve is assessed, demonstrating that at least two IO curves need to be acquired with different pulse widths. Then, a two-stage SPE method is proposed. It estimates the IO curve by using Fisher information matrix (FIM) optimization in the first stage and subsequently estimates the membrane time constant as well as the coupling gain in the second stage. The procedure continues in a sequential manner until a stopping rule is satisfied. RESULTS: The results of 73 simulation cases confirm the satisfactory estimation of the membrane time constant and coupling gain with average absolute relative errors (AREs) of 6.2% and 5.3%, respectively, with an average of 344 pulses (172 pulses for each IO curve or pulse width). The method estimates the IO curves' lower and upper plateaus, mid-point, and slope with average AREs of 0.2%, 0.7%, 0.9%, and 14.5%, respectively. The conventional time constant estimation method based on the strength-duration (S-D) curve leads to 33.3% ARE, which is 27.0% larger than 6.2% ARE obtained through the proposed real-time FIM-based SPE method in this paper. CONCLUSIONS: SPE of the activation dynamics requires acquiring at least two IO curves with different pulse widths, which needs a controllable TMS (cTMS) device with adjustable pulse duration. SIGNIFICANCE: The proposed SPE method enhances the cTMS functionality, which can contribute novel insights in research and clinical studies.


Assuntos
Encéfalo , Estimulação Magnética Transcraniana , Cicloexanos , Mesilatos
20.
Cell Mol Life Sci ; 80(9): 248, 2023 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-37578596

RESUMO

Human erythroleukemic K562 cells represent the prototypical cell culture model of chronic myeloid leukemia (CML). The cells are pseudo-triploid and positive for the Philadelphia chromosome. Therefore, K562 cells have been widely used for investigating the BCR/ABL1 oncogene and the tyrosine kinase inhibitor, imatinib-mesylate. Further, K562 cells overexpress transferrin receptors (TfR) and have been used as a model for targeting cytotoxic therapies, via receptor-mediated endocytosis. Here, we have characterized K562 cells focusing on the karyotype of cells in prolonged culture, regulation of expression of TfR in wildtype (WT) and doxorubicin-resistant cells, and responses to histone deacetylase inhibition (HDACi). Karyotype analysis indicates novel chromosomes and gene expression analysis suggests a shift of cultured K562 cells away from patient-derived leukemic cells. We confirm the high expression of TfR on K562 cells using immunofluorescence and cell-surface receptor binding radioassays. Importantly, high TfR expression is observed in patient-derived cells, and we highlight the persistent expression of TfR following doxorubicin acquired resistance. Epigenetic analysis indicates that permissive histone acetylation and methylation at the promoter region regulates the transcription of TfR in K562 cells. Finally, we show relatively high expression of HDAC enzymes in K562 cells and demonstrate the chemotoxic effects of HDACi, using the FDA-approved hydroxamic acid, vorinostat. Together with a description of morphology, infrared spectral analysis, and examination of metabolic properties, we provide a comprehensive characterization of K562 cells. Overall, K562 cell culture systems remain widely used for the investigation of novel therapeutics for CML, which is particularly important in cases of imatinib-mesylate resistance.


Assuntos
Proteínas de Fusão bcr-abl , Leucemia Mielogênica Crônica BCR-ABL Positiva , Humanos , Mesilato de Imatinib/farmacologia , Mesilato de Imatinib/uso terapêutico , Células K562 , Proteínas de Fusão bcr-abl/genética , Transferrina , Pirimidinas/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Histona Desacetilases/metabolismo , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Receptores da Transferrina/genética , Cromossomos/metabolismo , Mesilatos/farmacologia , Apoptose
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