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1.
J Am Coll Cardiol ; 78(16): 1635-1654, 2021 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-34649702

RESUMO

Coronavirus disease-2019 (COVID-19) is associated with systemic inflammation, endothelial activation, and multiorgan manifestations. Lipid-modulating agents may be useful in treating patients with COVID-19. These agents may inhibit viral entry by lipid raft disruption or ameliorate the inflammatory response and endothelial activation. In addition, dyslipidemia with lower high-density lipoprotein cholesterol and higher triglyceride levels portend worse outcomes in patients with COVID-19. Upon a systematic search, 40 randomized controlled trials (RCTs) with lipid-modulating agents were identified, including 17 statin trials, 14 omega-3 fatty acids RCTs, 3 fibrate RCTs, 5 niacin RCTs, and 1 dalcetrapib RCT for the management or prevention of COVID-19. From these 40 RCTs, only 2 have reported preliminary results, and most others are ongoing. This paper summarizes the ongoing or completed RCTs of lipid-modulating agents in COVID-19 and the implications of these trials for patient management.


Assuntos
COVID-19/tratamento farmacológico , COVID-19/prevenção & controle , Ácidos Graxos Ômega-3/uso terapêutico , Ácidos Fíbricos/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Niacina/uso terapêutico , Amidas/farmacologia , Amidas/uso terapêutico , Ésteres/farmacologia , Ésteres/uso terapêutico , Ácidos Graxos Ômega-3/farmacologia , Ácidos Fíbricos/farmacologia , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Reguladores do Metabolismo de Lipídeos/farmacologia , Reguladores do Metabolismo de Lipídeos/uso terapêutico , Niacina/farmacologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Compostos de Sulfidrila/farmacologia , Compostos de Sulfidrila/uso terapêutico
2.
J Org Chem ; 86(20): 14232-14237, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34596412

RESUMO

Ball milling of aromatic, heteroaromatic, vinylic, and aliphatic esters with ethanol and calcium nitride afforded the corresponding primary amides in a transformation that was compatible with a variety of functional groups and maintained the integrity of a stereocenter α to carbonyl. This methodology was applied to α-amino esters and N-BOC dipeptide esters and also to the synthesis of rufinamide, an antiepileptic drug.


Assuntos
Amidas , Ésteres , Dipeptídeos
3.
Radiol Imaging Cancer ; 3(5): e200155, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34477453

RESUMO

Purpose To determine if amide proton transfer-weighted chemical exchange saturation transfer (APTW CEST) MRI is useful in the early assessment of treatment response in persons with triple-negative breast cancer (TNBC). Materials and Methods In this prospective study, a total of 51 participants (mean age, 51 years [range, 26-79 years]) with TNBC were included who underwent APTW CEST MRI with 0.9- and 2.0-µT saturation power performed at baseline, after two cycles (C2), and after four cycles (C4) of neoadjuvant systemic therapy (NAST). Imaging was performed between January 31, 2019, and November 11, 2019, and was a part of a clinical trial (registry number NCT02744053). CEST MR images were analyzed using two methods-magnetic transfer ratio asymmetry (MTRasym) and Lorentzian line shape fitting. The APTW CEST signals at baseline, C2, and C4 were compared for 51 participants to evaluate the saturation power levels and analysis methods. The APTW CEST signals and their changes during NAST were then compared for the 26 participants with pathology reports for treatment response assessment. Results A significant APTW CEST signal decrease was observed during NAST when acquisition at 0.9-µT saturation power was paired with Lorentzian line shape fitting analysis and when the acquisition at 2.0 µT was paired with MTRasym analysis. Using 0.9-µT saturation power and Lorentzian line shape fitting, the APTW CEST signal at C2 was significantly different from baseline in participants with pathologic complete response (pCR) (3.19% vs 2.43%; P = .03) but not with non-pCR (2.76% vs 2.50%; P > .05). The APTW CEST signal change was not significant between pCR and non-pCR at all time points. Conclusion Quantitative APTW CEST MRI depended on optimizing acquisition saturation powers and analysis methods. APTW CEST MRI monitored treatment effects but did not differentiate participants with TNBC who had pCR from those with non-pCR. © RSNA, 2021 Clinical trial registration no. NCT02744053 Supplemental material is available for this article. Keywords Molecular Imaging-Cancer, Molecular Imaging-Clinical Translation, MR-Imaging, Breast, Technical Aspects, Tumor Response, Technology Assessment.


Assuntos
Prótons , Neoplasias de Mama Triplo Negativas , Amidas , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Terapia Neoadjuvante , Projetos Piloto , Estudos Prospectivos , Neoplasias de Mama Triplo Negativas/diagnóstico por imagem
4.
J Agric Food Chem ; 69(38): 11470-11484, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34543010

RESUMO

The development of new green fungicides based on the structural optimization of natural products can effectively solve the problems of low safety and high pathogen resistance of traditional fungicides. In this paper, based on pyrazole amide compound h-I-9 with excellent fungicidal activity discovered in the previous work, a series of l-serine-derived pyrazole amide and waltherione alkaloid-derived pyrazole ester derivatives were synthesized. The structures were successively identified by 1H NMR, 13C NMR, high-resolution mass spectrometry, and X-ray single-crystal diffraction. The in vitro and in vivo fungicidal activity screening demonstrated that compound II-5 showed a good inhibition rate against Physalospora piricola. A transmission electron microscope and fluorescence microscope observation further revealed that compound II-5 may cause damage to the cell membranes and vacuoles, and the hyphae treated with II-5 could produce obvious and easily observed blue fluorescence. The succinate dehydrogenase (SDH) enzymatic activity and molecular docking simulation indicated that compounds I-3 and I-4 may be potential SDH inhibitors against Alternaria sp.


Assuntos
Alcaloides , Produtos Biológicos , Fungicidas Industriais , Alcaloides/farmacologia , Amidas/farmacologia , Produtos Biológicos/farmacologia , Ésteres , Fungicidas Industriais/farmacologia , Simulação de Acoplamento Molecular , Estrutura Molecular , Pirazóis/farmacologia , Serina , Relação Estrutura-Atividade , Succinato Desidrogenase/metabolismo
5.
Molecules ; 26(17)2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34500646

RESUMO

Arachidonylethanolamide (anandamide) acts as an endogenous ligand of cannabinoid receptors, while other N-acylethanolamines (NAEs), such as palmitylethanolamide and oleylethanolamide, show analgesic, anti-inflammatory, and appetite-suppressing effects through other receptors. In mammalian tissues, NAEs, including anandamide, are produced from glycerophospholipid via N-acyl-phosphatidylethanolamine (NAPE). The ɛ isoform of cytosolic phospholipase A2 (cPLA2) functions as an N-acyltransferase to form NAPE. Since the cPLA2 family consists of six isoforms (α, ß, γ, δ, ɛ, and ζ), the present study investigated a possible involvement of isoforms other than ɛ in the NAE biosynthesis. Firstly, when the cells overexpressing one of the cPLA2 isoforms were labeled with [14C]ethanolamine, the increase in the production of [14C]NAPE was observed only with the ɛ-expressing cells. Secondly, when the cells co-expressing ɛ and one of the other isoforms were analyzed, the increase in [14C]N-acyl-lysophosphatidylethanolamine (lysoNAPE) and [14C]NAE was seen with the combination of ɛ and γ isoforms. Furthermore, the purified cPLA2γ hydrolyzed not only NAPE to lysoNAPE, but also lysoNAPE to glycerophospho-N-acylethanolamine (GP-NAE). Thus, the produced GP-NAE was further hydrolyzed to NAE by glycerophosphodiesterase 1. These results suggested that cPLA2γ is involved in the biosynthesis of NAE by its phospholipase A1/A2 and lysophospholipase activities.


Assuntos
Etanolaminas/metabolismo , Fosfolipases A2/metabolismo , Isoformas de Proteínas/metabolismo , Aciltransferases/metabolismo , Amidas/metabolismo , Animais , Ácidos Araquidônicos/metabolismo , Linhagem Celular , Endocanabinoides/metabolismo , Etanolamina/metabolismo , Células HEK293 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ácidos Oleicos/metabolismo , Ácidos Palmíticos/metabolismo , Fosfatidiletanolaminas/metabolismo , Diester Fosfórico Hidrolases/metabolismo , Alcamidas Poli-Insaturadas/metabolismo
6.
J Enzyme Inhib Med Chem ; 36(1): 1996-2009, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34525898

RESUMO

Microtubule dynamics are crucial for multiple cell functions, and cancer cells are particularly sensitive to microtubule-modulating agents. Here, we describe the design and synthesis of a series of (Z)-2-(5-benzylidene-4-oxo-2-thioxothiazolidin-3-yl)-N-phenylacetamide derivatives and evaluation of their microtubule-modulating and anticancer activities in vitro. Proliferation assays identified I20 as the most potent of the antiproliferative compounds, with 50% inhibitory concentrations ranging from 7.0 to 20.3 µM with A549, PC-3, and HepG2 human cancer cell lines. Compound I20 also disrupted cancer A549 cell migration in a concentration-dependent manner. Immunofluorescence microscopy, transmission electron microscopy, and tubulin polymerisation assays suggested that compound I20 promoted protofilament assembly. In support of this possibility, computational docking studies revealed a strong interaction between compound I20 and tubulin Arg ß369, which is also the binding site for the anticancer drug Taxol. Our results suggest that (Z)-2-(5-benzylidene-4-oxo-2-thioxothiazolidin-3-yl)-N-phenylacetamide derivatives could have utility for the development of microtubule-stabilising therapeutic agents.


Assuntos
Acetatos/farmacologia , Amidas/farmacologia , Antineoplásicos/farmacologia , Descoberta de Drogas , Microtúbulos/efeitos dos fármacos , Rodanina/farmacologia , Moduladores de Tubulina/farmacologia , Células A549 , Acetatos/síntese química , Acetatos/química , Amidas/química , Antineoplásicos/síntese química , Antineoplásicos/química , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Microtúbulos/metabolismo , Estrutura Molecular , Polimerização/efeitos dos fármacos , Rodanina/análogos & derivados , Rodanina/química , Relação Estrutura-Atividade , Tubulina (Proteína)/metabolismo , Moduladores de Tubulina/síntese química , Moduladores de Tubulina/química
7.
Biomater Sci ; 9(19): 6555-6567, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34582536

RESUMO

Amino acid-based poly(ester amide) (PEA) has been utilized for various biomedical applications due to its tunable mechanical properties, good biocompatibility, and biodegradability. However, bioactive components have rarely been incorporated into the PEA structure, and there has been no systematic investigation of amino acid-based PEAs with branched structures. Herein, an in vivo metabolizable branched poly(ester amide) (BPEA) was synthesized from inositol (a natural growth factor) and amino acids for drug delivery in cancer therapy. The bioactive components, inositol, arginine, and phenylalanine, could improve the biocompatibility of the BPEA nanocarrier, and convert into other valuable biomolecules (phosphatidylinositol for cell signaling, functional protein, or other amino acids including ornithine, citrulline, and tyrosine) after accomplishing drug delivery and biodegradation. Paclitaxel (PTX) was encapsulated into BPEA nanocarriers to formulate drug-loaded BPEA nanoparticles (BPEA@PTX NPs). In vitro results indicated that BPEA@PTX NPs had a sub 100 nm size and could effectively inhibit the growth and migration of cancer cells. In vivo experiments further demonstrated significant suppression of tumor size compared with that with free PTX. Both in vitro and in vivo results confirmed the superior biosafety of BPEA, indicating that BPEA exhibits excellent biocompatibility and considerable potential as a drug carrier.


Assuntos
Nanopartículas , Neoplasias , Amidas/uso terapêutico , Aminoácidos , Linhagem Celular Tumoral , Portadores de Fármacos/uso terapêutico , Ésteres , Inositol/uso terapêutico , Neoplasias/tratamento farmacológico , Paclitaxel/uso terapêutico
9.
Molecules ; 26(17)2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34500600

RESUMO

Carbon-carbon bond forming reactions, such as aldol reaction and condensation, belong to extremely desired transformations as manifested by >25,000 entries in SciFinder. Their stereoselective variant requires the use of an appropriate catalyst with a strictly defined structure. Hence, chiral 2-azabicycloalkane-based catalysts were designed, synthesized and tested in a stereoselective aldol reaction between cyclic/acyclic ketone and p-nitrobenzaldehyde both in organic and aqueous media. Among catalysts containing a chiral bicyclic backbone, amide based on 2-azabicyclo[3.2.1]octane and pyrrolidine units showed the best catalytic activity and afforded aldol product in excellent chemical yields (up to 95%) and good diastereo- and enantioselectivity (dr 22:78, ee up to 63%).


Assuntos
Aminoácidos/química , Cicloparafinas/química , Poliaminas/química , Amidas/química , Carbono/química , Catálise , Cetonas/química , Pirrolidinas/química , Estereoisomerismo
10.
J Phys Chem B ; 125(39): 10928-10938, 2021 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-34559531

RESUMO

The dynamics and spectroscopy of N-methyl-acetamide (NMA) and trialanine in solution are characterized from molecular dynamics simulations using different energy functions, including a conventional point charge (PC)-based force field, one based on a multipolar (MTP) representation of the electrostatics, and a semiempirical DFT method. For the 1D infrared spectra, the frequency splitting between the two amide-I groups is 10 cm-1 from the PC, 13 cm-1 from the MTP, and 47 cm-1 from self-consistent charge density functional tight-binding (SCC-DFTB) simulations, compared with 25 cm-1 from experiment. The frequency trajectory required for the frequency fluctuation correlation function (FFCF) is determined from individual normal mode (INM) and full normal mode (FNM) analyses of the amide-I vibrations. The spectroscopy, time-zero magnitude of the FFCF C(t = 0), and the static component Δ02 from simulations using MTP and analysis based on FNM are all consistent with experiments for (Ala)3. Contrary to this, for the analysis excluding mode-mode coupling (INM), the FFCF decays to zero too rapidly and for simulations with a PC-based force field, the Δ02 is too small by a factor of two compared with experiments. Simulations with SCC-DFTB agree better with experiment for these observables than those from PC-based simulations. The conformational ensemble sampled from simulations using PCs is consistent with the literature (including PII, ß, αR, and αL), whereas that covered by the MTP-based simulations is dominated by PII with some contributions from ß and αR. This agrees with and confirms recently reported Bayesian-refined populations based on 1D infrared experiments. FNM analysis together with a MTP representation provides a meaningful model to correctly describe the dynamics of hydrated trialanine.


Assuntos
Alanina , Amidas , Teorema de Bayes , Conformação Molecular , Simulação de Dinâmica Molecular , Análise Espectral
11.
Mater Sci Eng C Mater Biol Appl ; 128: 112288, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474839

RESUMO

The bone extracellular matrix (ECM) is a composite scaffold having inorganic hydroxyapatite and organic collagen fibers. Synthetic bone repair scaffolds that mimic the chemical composition of the native ECM and capable of delivering therapeutics are beneficial. In this study, we prepared intrinsically fluorescent organic-inorganic hybrid microparticle biomaterials by sol-gel process. Unlike the conventional Stöber process which requires an alkaline condition for microparticle formation, an acidic condition in the presence of a biodegradable poly(ester amide) (PEA) polymer was used to prepare silica and tertiary bioactive glass hybrids. During their preparation, one or two model drugs were loaded in the microparticles. Our results showed that a gelation temperature between 40 °C-60 °C and the inclusion of PEA were critical for microparticle formation. Unexpectedly, the hybrid microparticles were fluorescent with tunable emission by changing the excitation wavelengths ranging from 300 to 565 nm for potential multiplex imaging. Gene expression studies showed that the hybrid materials induce osteogenic differentiation of 10T1/2 cells without adding exogenous biochemical factors. The bioactivity of the inorganic phase and the dual drug release from homogenous, biodegradable, biocompatible, osteoinductive, and intrinsically fluorescent microparticles may offer a unique platform for bone regeneration and therapy.


Assuntos
Preparações Farmacêuticas , Tecidos Suporte , Amidas , Materiais Biocompatíveis/farmacologia , Regeneração Óssea , Ésteres , Osteogênese
12.
J Food Sci ; 86(9): 3951-3963, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34383315

RESUMO

Alkylamides, as the representative hemp flavor and active ingredients, can reflect the quality of Zanthoxylum bungeanum Maxim. However, conjugated triene structure exists in alkylamides, which is easy to be oxidized and decomposed in air, making it difficult to quantify. In this study, a method for the quantitative determination of alkylamides by 1 H-NMR technology was developed with 85% ethanol as the best extraction solvent, CDCl3 as the best deuterium dissolution reagent, pyrazine as the internal standard, and triple peaks of hydrogen protons on the amide bond at δ 6.33 ppm as the quantitative signal peak. Meanwhile, methodological verification was carried out to prove the reliability and effectiveness of the method. On this basis, the contents of alkylamides in nine germplasms of Zanthoxylum with monthly dynamics were obtained. The results showed that the alkylamides of Hancheng stingless Z. bungeanum (HC) exhibited the highest content in August (51.92 ± 0.96 mg/g), while the lowest was FG in June (1.23 ± 0.21 mg/g). The results of 1 H-NMR corresponded to those of HPLC, and the effectiveness of this method was verified. Accumulation dynamic results show that the best harvest period of Z. bungeanum is July and August. Moreover, the quality of nine varieties of Zanthoxylum bungeanum from a common garden was evaluated by the established 1 H-NMR fingerprint and chemometric analyses. The results showed that Hancheng stingless Z. bungeanum was the best germplasm. This study provides a new strategy for the quantitative determination of alkylamides in Z. bungeanum and improves the quality evaluation system of Z. bungeanum. PRACTICAL APPLICATION: The results provide a new research idea for the analysis of important chemical components of Z. bungeanum. Meanwhile, the study provides a scientific basis for the quality evaluation and high-quality germplasm resources of Z. bungeanum.


Assuntos
Amidas , Análise de Alimentos , Espectroscopia de Ressonância Magnética , Zanthoxylum , Amidas/análise , Cromatografia Líquida de Alta Pressão , Análise de Alimentos/métodos , Prótons , Reprodutibilidade dos Testes , Zanthoxylum/química
13.
Nat Commun ; 12(1): 4996, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404793

RESUMO

Between 10 and 20 million people worldwide are infected with the human T-cell lymphotropic virus type 1 (HTLV-1). Despite causing life-threatening pathologies there is no therapeutic regimen for this deltaretrovirus. Here, we screened a library of integrase strand transfer inhibitor (INSTI) candidates built around several chemical scaffolds to determine their effectiveness in limiting HTLV-1 infection. Naphthyridines with substituents in position 6 emerged as the most potent compounds against HTLV-1, with XZ450 having highest efficacy in vitro. Using single-particle cryo-electron microscopy we visualised XZ450 as well as the clinical HIV-1 INSTIs raltegravir and bictegravir bound to the active site of the deltaretroviral intasome. The structures reveal subtle differences in the coordination environment of the Mg2+ ion pair involved in the interaction with the INSTIs. Our results elucidate the binding of INSTIs to the HTLV-1 intasome and support their use for pre-exposure prophylaxis and possibly future treatment of HTLV-1 infection.


Assuntos
Antivirais/química , Antivirais/farmacologia , Microscopia Crioeletrônica , Infecções por HTLV-I/tratamento farmacológico , Vírus Linfotrópico T Tipo 1 Humano/efeitos dos fármacos , Amidas , Domínio Catalítico , Deltaretrovirus , Farmacorresistência Viral/efeitos dos fármacos , Integrase de HIV/efeitos dos fármacos , HIV-1 , Compostos Heterocíclicos com 3 Anéis , Vírus Linfotrópico T Tipo 1 Humano/genética , Humanos , Naftiridinas/farmacologia , Piperazinas , Piridonas , Proteínas Recombinantes
14.
Nat Prod Res ; 35(16): 2655-2659, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34414848

RESUMO

Two novel amide glycosides, named oleraciamide E (1) and oleraciamide F (2), were isolated from the Portulaca oleracea L. Their structures were determined by means of 1D and 2D NMR spectroscopic and UHPLC-ESI-TOF-MS methods. Oleraciamide E (1) exhibited anticholinesterase activity with IC50 values of 52.43 ± 0.33 µM, and presented scavenging activity in 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical quenching assay, with the IC50 values of 24.64 ± 0.33 µM.


Assuntos
Amidas , Sequestradores de Radicais Livres , Glicosídeos , Portulaca , Amidas/isolamento & purificação , Amidas/farmacologia , Sequestradores de Radicais Livres/isolamento & purificação , Sequestradores de Radicais Livres/farmacologia , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Portulaca/química , Espectrometria de Massas por Ionização por Electrospray
16.
Int J Mol Sci ; 22(16)2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34445417

RESUMO

This study aimed to assess the neuro-regenerative properties of co-ultramicronized PEALut (Glialia®), composed of palmitoylethanolamide (PEA) and the flavonoid luteolin (Lut), in an in vivo model of traumatic brain injury (TBI) and patients affected by moderate TBI. An increase in neurogenesis was seen in the mice at 72 h and 7 d after TBI. The co-ultra PEALut treatment helped the neuronal reconstitution process to restore the basal level of both novel and mature neurons; moreover, it induced a significant upregulation of the neurotrophic factors, which ultimately led to progress in terms of memory recall during behavioral testing. Moreover, our preliminary findings in a clinical trial suggested that Glialia® treatment facilitated neural recovery on working memory. Thus, co-ultra PEALut (Glialia®) could represent a valuable therapeutic agent for intensifying the endogenous repair response in order to better treat TBI.


Assuntos
Amidas/administração & dosagem , Lesões Encefálicas Traumáticas/tratamento farmacológico , Etanolaminas/administração & dosagem , Luteolina/administração & dosagem , Neurogênese/efeitos dos fármacos , Ácidos Palmíticos/administração & dosagem , Administração Oral , Adulto , Idoso , Amidas/farmacologia , Animais , Lesões Encefálicas Traumáticas/etiologia , Lesões Encefálicas Traumáticas/psicologia , Modelos Animais de Doenças , Quimioterapia Combinada , Etanolaminas/farmacologia , Feminino , Humanos , Luteolina/farmacologia , Masculino , Memória de Curto Prazo/efeitos dos fármacos , Camundongos , Pessoa de Meia-Idade , Teste do Labirinto Aquático de Morris/efeitos dos fármacos , Ácidos Palmíticos/farmacologia , Distribuição Aleatória , Aprendizagem Espacial/efeitos dos fármacos , Resultado do Tratamento
17.
J Infect Public Health ; 14(9): 1247-1253, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34464921

RESUMO

OBJECTIVE: To assess the efficacy of Favipiravir compared to the standard therapy in treating patients with severe COVID-19 infection. METHODS: This is a retrospective cohort of patients with COVID-19 pneumonia who were treated with favipiravir, versus comparison group that received the standard of care. RESULTS: A total of 226 patients were included; 110 patients received favipiravir and 116 patients received standard of care. Patients who received favipiravir had longer time to recovery (14.2 ± 8.8 versus 12.8 ± 5.2, p = 0.17). Favipiravir was associated with an improved early day 14 mortality (4 [3.6%] versus 11 [9.5%]), p = 0.008), but was associated with a higher day 28 mortality (26 [23.6%] versus 11 [9.5%], p = 0.02). The overall mortality was higher in the favipiravir versus the standard of care group but difference was not statistically significant (33 [30.0%] versus 24 [20.7%], p = 0.10). CONCLUSION: The addition of favipiravir to standard of care was not associated with any improvement in clinical outcomes or mortality. Larger randomized controlled clinical trials are needed to further assess the efficacy of favipiravir.


Assuntos
COVID-19 , Amidas , Antivirais/uso terapêutico , Humanos , Pirazinas , Estudos Retrospectivos , SARS-CoV-2 , Padrão de Cuidado , Resultado do Tratamento
18.
Int Immunopharmacol ; 99: 108043, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34426105

RESUMO

BACKGROUND: Regarding the COVID-19 pandemic, potential therapeutic agents are being evaluated almost every day. Ciclosporin, a calcineurin inhibitor, is characterized by beneficial antiviral and immunomodulatory effects. The present study aimed to evaluate the efficacy of ciclosporin in managing COVID-19. METHODS: This study was a prospective non-controlled clinical trial carried out on 20 patients. Confirmed COVID-19 patients received two doses of ciclosporin (10 mg/kg and 5 mg/kg injections) 24 h apart. Mortality rate and the lengths of intensive care unit (ICU) and hospital stays were assessed for all 20 patients. RESULTS: The mortality rate and the need for mechanical ventilation were calculated as 50%. The percentage of ICU admission was 70%. The lengths of ICU and hospital stays were 8.13 ± 6.81 and 14.25 ± 8.55 days, respectively. The levels of ferritin and white blood cells were significantly higher after injecting the second dose of ciclosporin. Seven patients (35%) had radiologically improved lungs after ciclosporin therapy. CONCLUSION: It seems that the protocol of two doses of ciclosporin in combination with favipiravir does not have favorable effects among COVID-19 patients that do not respond to dexamethasone. Controlled trials are needed to confirm the results.


Assuntos
Amidas/uso terapêutico , Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , Ciclosporina/uso terapêutico , Pirazinas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Dexametasona/uso terapêutico , Monitoramento de Medicamentos , Quimioterapia Combinada , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Pandemias , Estudos Prospectivos , Respiração Artificial , SARS-CoV-2 , Resultado do Tratamento , Adulto Jovem
19.
J Environ Manage ; 298: 113466, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34371223

RESUMO

Novel highly porous nanoparticle materials are increasingly being applied in adsorption processes, but they need to be supported by robust matrixes to maintain their functionality. We present a study of hosting graphene oxide (GO) particles on polyether block amide (PEBA) melt electrospun fibers and applying such composite matrix to the adsorption of the cationic dye (crystal violet) from water. Various amounts of GO (from 0.5 to 2.0%) were mixed into pure PEBA and electrospun by melt electrospinning obtaining micro fibrous matrixes. These were characterized for morphology (SEM), chemical composition (FTIR), crystallinity (XRD), and wetting behavior (WCA). The increasing amount of GO adversely affected fiber diameter (reduced from 13.18 to 4.38 µm), while the hydrophilic properties (Water contact angle decrease from 109 to 76°) and overall dye adsorption was increased. Efficient adsorption has been demonstrated, reaching approximately 100 % removal efficiency using a 2% GO composite matrix at a dose of 40 mg/l and pH of 10. Further increase of GO concentration in polymer is not feasible due to instability in the electrospinning process.


Assuntos
Grafite , Poluentes Químicos da Água , Adsorção , Amidas , Elastômeros , Águas Residuárias
20.
Eur J Neurosci ; 54(6): 5932-5950, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34396611

RESUMO

The peroxisome proliferator-activated receptor alpha (PPARα) is a nuclear receptor that has been linked to the modulation of several physiological functions, including the sleep-wake cycle. The PPARα recognizes as endogenous ligands the lipids oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), which in turn, if systemically injected, they exert wake-promoting effects. Moreover, the activation of PPARα by the administration of OEA or PEA increases the extracellular contents of neurotransmitters linked to the control of wakefulness; however, the role of PPARα activated by OEA or PEA on additional biochemicals related to waking regulation, such as acetylcholine (ACh) and 5-hydroxytryptamine (5-HT), has not been fully studied. Here, we have investigated the effects of treatments of OEA or PEA on the contents of ACh and 5-HT by using in vivo microdialysis techniques coupled to HPLC means. For this purpose, OEA or PEA were systemically injected (5, 10 or 30 mg/kg; i.p.), and the levels of ACh and 5-HT were collected from the basal forebrain, a wake-related brain area. These pharmacological treatments significantly increased the contents of ACh and 5-HT as determined by HPLC procedures. Interestingly, PPARα antagonist MK-886 (30 mg/kg; i.p.) injected before the treatments of OEA or PEA blocked these outcomes. Our data suggest that the activation of PPARα by OEA or PEA produces significant changes on ACh and 5-HT levels measured from the basal forebrain and support the conclusion that PPARα is a suitable molecular element involved in the regulation of wake-related neurotransmitters.


Assuntos
PPAR alfa , Serotonina , Acetilcolina , Amidas , Encéfalo/metabolismo , Endocanabinoides , Etanolaminas , Ácidos Oleicos , PPAR alfa/metabolismo , Ácidos Palmíticos
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