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1.
Poult Sci ; 98(8): 3304-3312, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-30941414

RESUMO

Five hundred and forty 19-wk-old HyLine Brown laying hens were randomly distributed to 6 dietary treatments and fed 1of 6 corn-soybean meal-based diets added into choline with 0, 425, 850, 1,700, 3,400, and 6,800 mg/kg to investigate effects of dietary choline supplementation on lipid profiles of egg yolk, serum and liver, and hepatic redox status of laying hens. Yolk weight and total lipid, triglyceride, cholesterol and phosphatidylcholine, serum triglyceride, cholesterol, apolipoprotein B 100 (apoB 100), and very low density lipoprotein (VLDL), and liver relative weight, total lipid, triglyceride and apoB 100 as well as hepatic total superoxide dismutase and glutathione peroxidase (GSH-Px) activities, total antioxidant capacity (T-AOC), and malondialdehyde (MDA) in laying hens at weeks 58 and 68 of age were determined. The differences (P < 0.001) were caused by choline treatments in yolk phosphatidylcholine (at 850 mg/kg or more choline), serum VLDL, and liver triglyceride (at 1,700 and 3,400 mg/kg choline) of birds, at weeks 58 and 68 of age, and yolk total lipids were elevated (P < 0.05) by supplemental choline at 3,400 mg/kg whereas liver total lipids were reduced (P < 0.05) by 1,700 and 3,400 mg/kg choline addition. Hens fed diets supplemented choline had higher (P = 0.005) liver GSH-Px activity (with 3,400 mg/kg choline) and greater (P = 0.014) T-AOC (with 1,700 mg/kg choline) than those fed diets with 0 and 425 mg/kg choline addition. Choline affected serum VLDL, liver total lipid, triglyceride and apoB 100 at weeks 58 and 68 of age and hepatic GSH-Px activity, T-AOC and MDA at week 68 of age quadratically (P < 0.05), whereas it influenced total lipid and phosphatidylcholine of egg yolk linearly (P < 0.05) and quadratically (P < 0.05). In conclusion, dietary choline supplementation elevated yolk total lipid and phosphatidylcholine and serum VLDL, reduced liver total lipid and triglyceride, and enhanced hepatic GSH-Px activity and T-AOC in laying hens.


Assuntos
Ração Animal/análise , Colina/farmacologia , Gema de Ovo/química , Lipídeos/sangue , Animais , Galinhas , Dieta/veterinária , Feminino , Glutationa Peroxidase/análise , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/metabolismo , Oxirredução/efeitos dos fármacos , Fosfatidilcolinas/análise , Distribuição Aleatória , Superóxido Dismutase/análise
2.
Nutrients ; 11(3)2019 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-30889905

RESUMO

BACKGROUND: Choline is essential for the synthesis of liver phosphatidylcholine (PC), parenchymal maintenance, bile formation, and lipoprotein assembly to secrete triglycerides. In choline deficiency, the liver accretes choline/PC at the expense of lung tissue, thereby impairing pulmonary PC homoeostasis. In cystic fibrosis (CF), exocrine pancreas insufficiency results in impaired cleavage of bile PC and subsequent fecal choline loss. In these patients, the plasma choline concentration is low and correlates with lung function. We therefore investigated the effect of choline supplementation on plasma choline/PC concentration and metabolism, lung function, and liver fat. METHODS: 10 adult male CF patients were recruited (11/2014⁻1/2016), and orally supplemented with 3 × 1 g choline chloride for 84 (84⁻91) days. Pre-/post-supplementation, patients were spiked with 3.6 mg/kg [methyl-D9]choline chloride to assess choline/PC metabolism. Mass spectrometry, spirometry, and hepatic nuclear resonance spectrometry served for analysis. RESULTS: Supplementation increased plasma choline from 4.8 (4.1⁻6.2) µmol/L to 10.5 (8.5⁻15.5) µmol/L at d84 (p < 0.01). Whereas plasma PC concentration remained unchanged, D9-labeled PC was decreased (12.2 [10.5⁻18.3] µmol/L vs. 17.7 [15.5⁻22.4] µmol/L, p < 0.01), indicating D9-tracer dilution due to higher choline pools. Supplementation increased Forced Expiratory Volume in 1 second percent of predicted (ppFEV1) from 70.0 (50.9⁻74.8)% to 78.3 (60.1⁻83.9)% (p < 0.05), and decreased liver fat from 1.58 (0.37⁻8.82)% to 0.84 (0.56⁻1.17)% (p < 0.01). Plasma choline returned to baseline concentration within 60 h. CONCLUSIONS: Choline supplementation normalized plasma choline concentration and increased choline-containing PC precursor pools in adult CF patients. Improved lung function and decreased liver fat suggest that in CF correcting choline deficiency is clinically important. Choline supplementation of CF patients should be further investigated in randomized, placebo-controlled trials.


Assuntos
Deficiência de Colina/tratamento farmacológico , Colina/uso terapêutico , Fibrose Cística/tratamento farmacológico , Volume Expiratório Forçado/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Adolescente , Adulto , Colina/sangue , Colina/farmacologia , Deficiência de Colina/sangue , Deficiência de Colina/complicações , Fibrose Cística/sangue , Fibrose Cística/patologia , Fibrose Cística/fisiopatologia , Suplementos Nutricionais , Insuficiência Pancreática Exócrina/sangue , Insuficiência Pancreática Exócrina/complicações , Insuficiência Pancreática Exócrina/tratamento farmacológico , Fígado Gorduroso/sangue , Fígado Gorduroso/etiologia , Fígado Gorduroso/prevenção & controle , Humanos , Fígado/metabolismo , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fosfatidilcolinas/sangue , Triglicerídeos/sangue , Adulto Jovem
3.
Nutrients ; 11(2)2019 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-30759768

RESUMO

Dlx3 (distal-less homeobox 3) haploinsufficiency in mice has been shown to result in restricted fetal growth and placental defects. We previously showed that maternal choline supplementation (4X versus 1X choline) in the Dlx3+/- mouse increased fetal and placental growth in mid-gestation. The current study sought to test the hypothesis that prenatal choline would modulate indicators of placenta function and development. Pregnant Dlx3+/- mice consuming 1X (control), 2X, or 4X choline from conception were sacrificed at embryonic (E) days E10.5, E12.5, E15.5, and E18.5, and placentas and embryos were harvested. Data were analyzed separately for each gestational day controlling for litter size, fetal genotype (except for models including only +/- pups), and fetal sex (except when data were stratified by this variable). 4X choline tended to increase (p < 0.1) placental labyrinth size at E10.5 and decrease (p < 0.05) placental apoptosis at E12.5. Choline supplementation decreased (p < 0.05) expression of pro-angiogenic genes Eng (E10.5, E12.5, and E15.5), and Vegf (E12.5, E15.5); and pro-inflammatory genes Il1b (at E15.5 and 18.5), Tnfα (at E12.5) and Nfκb (at E15.5) in a fetal sex-dependent manner. These findings provide support for a modulatory effect of maternal choline supplementation on biomarkers of placental function and development in a mouse model of placental insufficiency.


Assuntos
Apoptose/efeitos dos fármacos , Colina/farmacologia , Suplementos Nutricionais , Inflamação/metabolismo , Neovascularização Fisiológica/efeitos dos fármacos , Insuficiência Placentária , Fenômenos Fisiológicos da Nutrição Animal , Animais , Biomarcadores , Colina/administração & dosagem , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Proteínas de Homeodomínio/genética , Camundongos , Camundongos Knockout , Neovascularização Fisiológica/fisiologia , Gravidez , Fenômenos Fisiológicos da Nutrição Pré-Natal , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fatores de Transcrição/genética
4.
Ticks Tick Borne Dis ; 10(3): 568-574, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30733146

RESUMO

Theileria equi and Babesia caballi are tick-borne apicomplexan haemoprotozoan parasites of equines and are responsible for considerable economic losses to stakeholders. Chemotherapeutic drugs that are available not only require multiple dosages but also prompt multiple organ toxicity in treated host though incapable of clearing parasitaemia completely. In this study, we have screened the in vitro inhibitory efficacy of four different drug molecules (o-choline, DABCO®, lumefantrine and eugenol) against T. equi and B. caballi, targeting different parasite metabolism pathways. Imidocarb dipropionate and diminazene aceturate were used as reference control drugs. The 50% in vitro growth inhibitory concentration (IC50) of lumefantrine, o-choline, DABCO® and eugenol for T. equi were: 30.90 µM; 84.38 µM; 443 µM; 120 µM and for B. caballi growth inhibition were: 5.58 µM; 135.29 µM; 150 µM; 197.05 µM, respectively. Imidocarb dipropionate inhibited the in vitro growth of T. equi at IC50 of 257.5 nM, while diminazene aceturate inhibited the in vitro growth of B. caballi at IC50 of 22 nM. DABCO® and eugenol were not so effective in inhibiting the in vitro growth of T. equi and B. caballi, while lumefantrine and o-choline significantly (p ≤ 0.05) inhibited the in vitro growth of these piroplasms targeting haem digestion and parasite membrane phospholipid synthesis.


Assuntos
Babesia/efeitos dos fármacos , Colina/farmacologia , Lumefantrina/farmacologia , Redes e Vias Metabólicas/efeitos dos fármacos , Theileria/efeitos dos fármacos , Animais , Babesia/crescimento & desenvolvimento , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Hemoglobinas/metabolismo , Cavalos , Concentração Inibidora 50 , Lactatos/metabolismo , Fosfolipídeos/metabolismo , Filogenia , Theileria/crescimento & desenvolvimento
5.
Talanta ; 197: 567-577, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-30771977

RESUMO

With the development of deep eutectic solvents (DESs), more DES-based functional materials have been explored and applied in various areas. In this work, a novel choline chloride-acrylic acid (ChCl-AA) DES polymer, on a 2D magnetic base, was prepared for the recognition of ß-lactoglobulin (ß-LG) biomacromolecules in milk and for the inhibition of common bacteria such as Escherichia coli (E. coli), Pseudomonas fluorescens (P. fluorescens), Staphylococcus aureus (S. aureus), and Bacillus subtilis (B. subtilis). The ChCl-AA DESs were polymerized on the surface of 2D MoS2 sheets doped with nano Fe3O4 particles, and the resulting polymer was abbreviated poly(ChCl-AA DES)@Fe3O4@MoS2. The free energy (ΔG=-92) of ChCl-AA DES was calculated using the Gaussian software, the composition and structure of poly(ChCl-AA DES)@Fe3O4@MoS2 were characterized by field emission scanning electron microscopy, transmission electron microscopy, etc., the qualitative and quantitative analyses of ß-LG were done by fluorescence spectra, sodium dodecyl sulfate polyacrylamide gel electrophoresis and high performance liquid chromatography, and the bioactivity of bacteria was analyzed by flat colony counting. Based on the present analysis, poly(ChCl-AA DES)@Fe3O4@MoS2 specifically recognized ß-LG in a good fitting Langmuir isotherm (R2 = 0.9909) and second-order kinetic model (R2 = 0.9989) by affinity, and evidently inhibited three bacteria, namely, E. coil (65%), S. aureus (50%), and B. subtilis (54%), effectively reducing the relative colony number. As the poly(ChCl-AA DES)@Fe3O4@MoS2 material did not only exhibit specific recognition of biomacromolecules, but also had an antimicrobial effect against common bacteria, it could be an ideal separation media or carrier for biomacromolecules in real samples.


Assuntos
Acrilatos/química , Antibacterianos/análise , Colina/química , Lactoglobulinas/análise , Leite/química , Polímeros/química , Acrilatos/farmacologia , Animais , Antibacterianos/farmacologia , Colina/farmacologia , Dissulfetos/química , Dissulfetos/farmacologia , Compostos Férricos/química , Compostos Férricos/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Leite/microbiologia , Molibdênio/química , Molibdênio/farmacologia , Tamanho da Partícula , Polímeros/farmacologia , Solventes/química , Propriedades de Superfície
6.
J Agric Food Chem ; 67(7): 2004-2011, 2019 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-30715867

RESUMO

It is of great significance to explore novel applications of renewable resources. In this study, a rosin-based anionic surfactant (abbreviated R-11-2-Na), which contains a large hydrophobic group of 30 carbon atoms, was synthesized. R-11-2-Na forms wormlike micelles in the presence of the equimolar organic salt choline chloride, endowing solutions with strong viscoelasticity. The wormlike micellar solutions were investigated using rheology, small-angle X-ray scattering, and freeze-fracture transmission electron microscopy (FF-TEM) methods at 25 °C. Due to the strong van der Waals interactions caused by the large hydrophobic group contained in R-11-2-Na, the zero-shear viscosity (η0) of solutions showed extremely strong dependence on the concentration with an exponent of 23.4. The cross-sectional diameter of the wormlike micelles in the present system was significantly larger than that of the wormlike micelles formed by surfactants containing conventional alkyl tails. This finding may be attributed to the steric hindrance brought by the bulky and rigid dehydroabietic acid unit in the hydrophobic part. The wormlike micelles also showed high tolerance to the organic salt concentration. The present study reveals the notable qualities of rosin-based derivatives in forming complex fluids and facilitates new utilizations of forest resources.


Assuntos
Resinas Vegetais/química , Reologia , Tensoativos/química , Substâncias Viscoelásticas/química , Ânions , Colina/farmacologia , Interações Hidrofóbicas e Hidrofílicas , Micelas , Microscopia Eletrônica de Transmissão/métodos , Viscosidade
7.
Eur J Pharmacol ; 847: 72-82, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30689994

RESUMO

Defect in one-carbon metabolism is one of the multiple underlying pathological pathways contributing to NAFLD pathogenesis. Hence, our study was designed to examine whether different one-carbon donors; betaine, choline, and folic acid would possess beneficial effects in NAFLD treatment. Rats were fed with high fat diet and NAFLD rats were orally treated with different doses of betaine or choline or folic acid for 28 days. All used one-carbon donors had dose-dependent ameliorating effects on NAFLD as they succeeded to reduce body and relative liver weights, serum lipids and liver enzymes. These were accompanied by decreasing hepatic fat accumulation and amending hepatic histological structure. They also improved serum and hepatic redox systems (total glutathione (tGSH), reduced GSH, oxidized GSSG, and GSH/GSSG ratio), hepatic S-adenosylmethionine/S-adenosyl homocysteine (SAM/SAH) ratio and increased hepatic global DNA methylation. There were some discrepancies in the dose and the extent of their effect, where folic acid showed the most prominent effects that could be mediated through the significant surge in hepatic SAM/SAH ratio and better efficient correction of one-carbon metabolism than the other donors. Thus, one-carbon donors can be strongly considered in NAFLD management and might influence the whole therapeutic approaches of fatty liver diseases.


Assuntos
Carbono/farmacologia , Fígado/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Animais , Betaína/farmacologia , Colina/farmacologia , Metilação de DNA/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Suplementos Nutricionais , Ácido Fólico/farmacologia , Glutationa/metabolismo , Homocisteína/metabolismo , Fígado/metabolismo , Masculino , Hepatopatia Gordurosa não Alcoólica/metabolismo , Ratos , Ratos Wistar , S-Adenosilmetionina/metabolismo
8.
Curr Radiopharm ; 12(1): 88-92, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30117406

RESUMO

OBJECTIVE: Glioblastoma multiforme (GBM) represents the most common and malignant glioma, accounting for 45%-50% of all gliomas. The median survival time for patients with glioblastoma is only 12-15 months after surgical, chemioterapic and radiotherapic treatment; a correct diagnosis is naturally fundamental to establish a rapid and correct therapy. Non-invasive imaging plays a pivotal role in each phase of the diagnostic workup of patients with suspected for diagnosis. The aim of this case report was to describe the potential clinical impact of 18F-fluorocholine (FCH) PET/CT in the assessment of a cystic GBM mimicking a spontaneous hemorrhage. METHODS: a 57 years-old male with intraparenchymal hemorrhage at CT imaging initially in reduction ad serial imaging and suspected right fronto-temporo-parietal lesion at MRI underwent dynamic and static (60' after tracer injection) FCH PET/CT of the brain. RESULTS: FCH PET/CT showed rapid tracer uptake after few second from injection at dynamic acquisition and consequent incremental mild uptake at static imaging after 60 minutes at the level of oval formation in the right cerebral hemisphere characterized by annular and peripheral high metabolic activity. The central region of the lesion was characterized by the absence 18F-FCH uptake most likely due to blood component. The patient underwent surgery for tumor removal; the histopathological examination confirmed the suspect of GBM. Chemo-radiotherapic adjuvant protocol according to Stupp protocol was therefore administrated; to date the patient is alive without any progression disease at 5 months from treatment. CONCLUSION: In this case report FCH PET/CT represented the final diagnostic technique to confirm the suspicious of a cystic GBM. Our case demonstrated the potential role of 18F-FCH PET/CT for discrimination of higher proliferation area over intraparenchymal hemorrhage, supporting the potential use of this imaging biomarker in surgical or radiosurgical approach. Obviously, further prospective studies are needed to confirm this role and to exactly define possible routinely applications.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Colina/análogos & derivados , Glioblastoma/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/farmacologia , Neoplasias Encefálicas/cirurgia , Hemorragia Cerebral/diagnóstico por imagem , Colina/farmacologia , Diagnóstico Diferencial , Glioblastoma/cirurgia , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade
9.
Mol Neurobiol ; 56(6): 3882-3896, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30220058

RESUMO

Rett syndrome (RTT) is a postnatal neurodevelopmental disorder that primarily affects girls, with 95% of RTT cases resulting from mutations in the methyl-CpG-binding protein 2 (MECP2) gene. Choline, a dietary micronutrient found in most foods, has been shown to be important for brain development and function. However, the exact effects and mechanisms are still unknown. We found that 13 mg/day (1.7 × required daily intake) of postnatal choline treatment to Mecp2-conditional knockout mice rescued not only deficits in motor coordination, but also their anxiety-like behaviour and reduced social preference. Cortical neurons in the brains of Mecp2-conditional knockout mice supplemented with choline showed enhanced neuronal morphology and increased density of dendritic spines. Modelling RTT in vitro by knocking down the expression of the MeCP2 protein with shRNA, we found that choline supplementation to MeCP2-knockdown neurons increased their soma sizes and the complexity of their dendritic arbors. Rescue of the morphological defects could lead to enhanced neurotransmission, as suggested by an observed trend of increased expression of synaptic proteins and restored miniature excitatory postsynaptic current frequency in choline-supplemented MeCP2-knockdown neurons. Through the use of specific inhibitors targeting each of the known physiological pathways of choline, synthesis of phosphatidylcholine from choline was found to be essential in bringing about the changes seen in the choline-supplemented MeCP2-knockdown neurons. Taken together, these data reveal a role of choline in modulating neuronal plasticity, possibly leading to behavioural changes, and hence, a potential for using choline to treat RTT.


Assuntos
Comportamento Animal/efeitos dos fármacos , Colina/farmacologia , Plasticidade Neuronal/efeitos dos fármacos , Síndrome de Rett/fisiopatologia , Animais , Córtex Cerebral/patologia , Espinhas Dendríticas/efeitos dos fármacos , Espinhas Dendríticas/patologia , Suplementos Nutricionais , Modelos Animais de Doenças , Feminino , Proteína 2 de Ligação a Metil-CpG/metabolismo , Camundongos Knockout , Neuritos/efeitos dos fármacos , Neuritos/metabolismo , Fosfatidilcolinas/biossíntese , Ratos Sprague-Dawley
10.
Food Chem ; 276: 768-775, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30409660

RESUMO

Sinapine is the main secondary metabolite present in rapeseed pomace (RSP) with its concentration being dependent on rapeseed processing, growing conditions, extraction parameters and the country of origin. Here we report, the concentration of sinapine from an extract of defatted RSP harvested in the North East of Scotland. Using liquid chromatography tandem mass spectrometry, the most abundant phenolic compound in the RSP extract was, as expected, sinapine (109.1 mg/g RSP extract). Additionally, sinapic, caffeic, ferulic and syringic acids were identified (0.159-3.91 mg/g RSP extract). Sinapine together with the phenolics at the concentration present in the RSP extract, exhibited ≥50% activity relative to the extract in antioxidant assays. Furthermore, sinapine provided plasmid DNA (pBR322) protection, from 2,2'-azobis(2-amidinopropane) dihydrochloride and inhibited acetylcholinesterase activity by 85%. Molecular docking was utilised to explain the inhibitory activity. RSP can be an excellent source of bioactive compounds for pharmaceuticals, food additive and nutraceutical applications.


Assuntos
Antioxidantes/farmacologia , Brassica rapa/química , Colina/análogos & derivados , Acetilcolinesterase/química , Acetilcolinesterase/metabolismo , Antioxidantes/análise , Colina/análise , Colina/química , Colina/farmacologia , Inibidores da Colinesterase/análise , Inibidores da Colinesterase/farmacologia , Cromatografia Líquida , Ácido Gálico/análogos & derivados , Ácido Gálico/análise , Simulação de Acoplamento Molecular , Fenóis/análise , Extratos Vegetais/análise , Extratos Vegetais/química , Escócia , Espectrometria de Massas em Tandem
11.
Carbohydr Polym ; 206: 187-197, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30553312

RESUMO

The utilization of natural compounds, such as phenolic acids and biopolymers, in the healthcare domain is gaining increasing attention. In this study, bacterial nanocellulose (BC) membranes were loaded with ionic liquids (ILs) based on phenolic acids. These ionic compounds, with improved solubility and bioavailability, were prepared by combining the cholinium cation with anions derived from caffeic, ellagic and gallic acids. The obtained BC-ILs membranes were homogeneous, conformable and their swelling ability agreed with the solubility of each IL. These membranes revealed a controlled ILs dissolution rate in the wet state and high antioxidant activity. In vitro assays performed with Raw 264.7 macrophages and HaCaT keratinocytes revealed that these novel BC-ILs membranes are non-cytotoxic and present relevant anti-inflammatory properties. Diffusion studies with Hanson vertical diffusion cells showed a prolonged release profile of the ILs from the BC membranes. Thus, this work, successfully demonstrates the potential of BC-ILs membranes for skin treatment.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Celulose/química , Líquidos Iônicos/farmacologia , Administração Cutânea , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/química , Antioxidantes/administração & dosagem , Antioxidantes/química , Ácidos Cafeicos/administração & dosagem , Ácidos Cafeicos/química , Ácidos Cafeicos/farmacologia , Linhagem Celular , Colina/administração & dosagem , Colina/química , Colina/farmacologia , Liberação Controlada de Fármacos , Módulo de Elasticidade , Ácido Elágico/administração & dosagem , Ácido Elágico/química , Ácido Elágico/farmacologia , Feminino , Ácido Gálico/administração & dosagem , Ácido Gálico/química , Ácido Gálico/farmacologia , Humanos , Líquidos Iônicos/administração & dosagem , Líquidos Iônicos/química , Membranas Artificiais , Camundongos , Nanoestruturas/química , Pele/efeitos dos fármacos
12.
Folia Neuropathol ; 56(3): 206-214, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30509042

RESUMO

INTRODUCTION: Perinatal maternal separation stress (PMSS) induces brain lipid peroxidation and reduction in endogenous antioxidants. The present study was designed to assess the brain oxidative stress (MDA) and protein thiol levels through various stages of aging in PMSS rat pups supplemented with choline with docosahexaenoic acid (DHA) or Clitoria ternatea (Linn) aqueous root extract (CTR). MATERIAL AND METHODS: Study groups, control, PMSS, PMSS + choline with DHA, PMSS + CTR (n = 6/group) were included in the study. Pups of PMSS groups were separated from their mothers for a period of 6 h/day for 30 days. PMSS + supplemented groups were treated as appropriate during the same period. Rats were sacrificed on day 30, 60, 90, 210 and 360. Brains were processed for MDA and protein thiol levels. RESULTS: Brain MDA levels were significantly increased in PMSS rats at day 30, 60 (p < 0.001), 90 (p < 0.01) and attenuated in PMSS pups supplemented with choline with DHA and CTR at day 30, 60 (p < 0.01), 90 (p < 0.01, p < 0.05) and 360 (p < 0.001) when compared to the same in age-matched controls and PMSS rats, respectively. Alternatively, brain protein thiol levels in PMSS rats were reduced in all age groups when compared to the same in age-matched controls. A significant increase in brain thiol levels was observed in supplemented groups at day 60 (p < 0.01) and 210 (p < 0.01, p < 0.05) when compared to the same in age-matched PMSS rats. CONCLUSIONS: PMSS causes enhanced brain lipid peroxidation (MDA levels) and reduces endogenous antioxidants. Supplementation of choline and DHA or CTR during PMSS in rats persistently attenuates brain oxidative stress through aging.


Assuntos
Encéfalo/metabolismo , Colina/farmacologia , Ácidos Docosa-Hexaenoicos/farmacologia , Privação Materna , Extratos Vegetais/farmacologia , Envelhecimento/metabolismo , Animais , Antioxidantes/farmacologia , Clitoria , Suplementos Nutricionais , Feminino , Masculino , Estresse Oxidativo/fisiologia , Raízes de Plantas , Ratos , Ratos Wistar , Estresse Psicológico/etiologia , Estresse Psicológico/metabolismo
13.
Front Immunol ; 9: 2448, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30410489

RESUMO

Dietary choline can impact systemic immunity, but it remains unclear whether this is primarily via direct impacts on immune cells or secondary effects of altered metabolic function. To determine whether increased choline concentrations (3.2, 8.2, 13.2 µM) in cell culture alter the function of bovine innate and adaptive immune cells, we isolated cells from dairy cows in early and mid-lactation as models of immuno-compromised and competent cells, respectively. Phagocytic and killing capacity of isolated neutrophils were linearly diminished with increasing doses of choline. In contrast, lymphocyte proliferation was linearly enhanced with increasing doses of choline. Furthermore, increasing doses of choline increased the mRNA abundance of genes involved in the synthesis of choline products (betaine, phosphatidylcholine, and acetylcholine) as well as muscarinic and nicotinic acetylcholine receptors in a quadratic and linear fashion for neutrophils and monocytes, respectively. Phagocytic and killing capacity of neutrophils and proliferation of lymphocytes were not affected by stage of lactation or its interaction with choline or LPS. In neutrophils from early lactation cows, choline linearly increased the mRNA abundance of muscarinic and nicotinic cholinergic receptors, whereas choline-supplemented monocytes from mid-lactation cows linearly increased the mRNA abundance of several genes coding for choline metabolism enzymes. These data demonstrate that choline regulates the inflammatory response of immune cells and suggest that the mechanism may involve one or more of its metabolic products.


Assuntos
Colina/farmacologia , Linfócitos/imunologia , Monócitos/imunologia , Neutrófilos/imunologia , RNA Mensageiro/análise , Acetilcolina/genética , Imunidade Adaptativa/efeitos dos fármacos , Animais , Betaína/metabolismo , Bovinos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Colina/metabolismo , Feminino , Imunidade Inata/efeitos dos fármacos , Inflamação/imunologia , Lactação , Fagocitose/efeitos dos fármacos , Fagocitose/imunologia , Fosfatidilcolinas/genética , Receptores Muscarínicos/genética , Receptores Nicotínicos/genética
14.
J Neurophysiol ; 120(6): 3217-3233, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30354793

RESUMO

Choline chloride is often, and N-methyl-d-glucamine (NMDG) sometimes, used to replace sodium chloride in studies of sodium-activated potassium channels. Given the high concentrations used in sodium replacement protocols, it is essential to test that it is not the replacement substances themselves, as opposed to the lack of sodium, that cause any observed effects. We therefore compared, in lobster stomatogastric neurons and leech Retzius cells, the effects of applying salines in which choline chloride replaced sodium chloride, and in which choline hydroxide or sucrose was added to normal saline. We also tested, in stomatogastric neurons, the effect of adding NMDG to normal saline. These protocols allowed us to measure the direct effects (i.e., effects not due to changes in sodium concentration or saline osmolarity or ionic strength) of choline on stomatogastric and leech currents, and of NMDG on stomatogastric currents. Choline directly reduced transient and sustained depolarization-activated outward currents in both species, and NMDG directly reduced transient depolarization-activated outward currents in stomatogastric neurons. Experiments with lower choline concentrations showed that adding as little as 150 mM (stomatogastric) or 5 mM (leech) choline reduced at least some depolarization-activated outward currents. Reductions in outward current with choline chloride or NMDG replacement alone are thus not evidence of sodium-activated potassium currents. NEW & NOTEWORTHY We show that choline or N-methyl-d-glucamine (NMDG) directly (i.e., not due to changes in extracellular sodium) decrease outward currents. Prior work studying sodium-activated potassium channels in which sodium was replaced with choline or NMDG without an addition control may therefore be artifactual.


Assuntos
Potenciais de Ação , Meglumina/farmacologia , Neurônios/metabolismo , Canais de Potássio/metabolismo , Potássio/metabolismo , Sódio/metabolismo , Animais , Colina/farmacologia , Sanguessugas , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Palinuridae
15.
J Nutr ; 148(10): 1513-1520, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30281112

RESUMO

Background: Phosphatidylethanolamine N-methyltransferase (PEMT) converts phosphatidylethanolamine to phosphatidylcholine. Pemt-/-/low density lipoprotein receptor (Ldlr)-/- mice have significantly reduced plasma lipids and are protected against atherosclerosis. Recent studies have shown that choline can be metabolized by the gut flora into trimethylamine-N-oxide (TMAO), which is an emerging risk factor for atherosclerosis. Objective: The objective of this study was to determine whether ectopic hepatic PEMT expression or choline supplementation would promote atherosclerosis in Pemt-/-/Ldlr-/- mice. Methods: Male 8- to 10-wk-old Pemt+/+/Ldlr-/- (SKO) and Pemt-/-/Ldlr-/- (DKO) mice were injected with an adeno-associated virus (AAV) expressing green fluorescent protein (GFP) or human PEMT and fed a Western diet (40% of calories from fat, 0.5% cholesterol) for 8 wk. In a separate experiment, 8- to 10-wk-old SKO and half of the DKO male mice were fed a Western diet with normal (3 g/kg) choline for 12 wk. The remaining DKO mice [choline-supplemented (CS) DKO] were fed a CS Western diet (10 g choline/kg). Plasma lipid concentrations, choline metabolites, and aortic atherosclerosis were measured. Results: Plasma cholesterol, plasma TMAO, and aortic atherosclerosis were reduced by 60%, 40%, and 80%, respectively, in DKO mice compared with SKO mice. AAV-PEMT administration increased plasma cholesterol and TMAO by 30% and 40%, respectively, in DKO mice compared with AAV-GFP-treated DKO mice. Furthermore, AAV-PEMT-injected DKO mice developed atherosclerotic lesions similar to SKO mice. In the second study, there was no difference in atherosclerosis or plasma cholesterol between DKO and CS-DKO mice. However, plasma TMAO concentrations were increased 2.5-fold in CS-DKO mice compared with DKO mice. Conclusions: Reintroducing hepatic PEMT reversed the atheroprotective phenotype of DKO mice. Choline supplementation did not increase atherosclerosis or plasma cholesterol in DKO mice. Our data suggest that plasma TMAO does not induce atherosclerosis when plasma cholesterol is low. Furthermore, this is the first report to our knowledge that suggests that de novo choline synthesis alters TMAO status.


Assuntos
Aterosclerose/metabolismo , Colesterol/sangue , Colina/farmacologia , Fígado/metabolismo , Metilaminas/sangue , Fosfatidiletanolamina N-Metiltransferase/metabolismo , Receptores de LDL/metabolismo , Animais , Aorta , Aterosclerose/etiologia , Aterosclerose/patologia , Aterosclerose/prevenção & controle , Colesterol na Dieta/administração & dosagem , Colina/metabolismo , Dieta Ocidental , Suplementos Nutricionais , Humanos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fosfatidiletanolamina N-Metiltransferase/farmacologia , Fosfatidiletanolaminas/metabolismo
16.
J Dairy Sci ; 101(11): 10374-10382, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30172410

RESUMO

Polymorphonuclear leukocytes (PMNL) are the first responders upon pathogen invasion and hence play an important role in inflammatory and immune responses. Rumen-protected methionine (MET) and choline (CHOL) during the peripartal period affect the immune response and inflammatory status in dairy cows to different extents. We aimed to examine the effect of MET and CHOL supply on expression of genes regulating key PMNL functions and associations with whole-blood immune challenge. Thirty multiparous Holstein cows from a larger cohort randomly assigned from -21 to 30 d relative to parturition to a basal control (CON) diet, CON plus MET at a rate of 0.08% of dry matter, or CON plus CHOL at 60 g/d were used. Blood was sampled at -10, 7, and 30 d relative to parturition for inflammatory biomarker analyses and PMNL isolation. Neutrophil and monocyte phagocytosis and oxidative burst in vitro were assessed in whole blood at 1, 7, and 28 d. Although neutrophil and monocyte phagocytosis did not differ, oxidative burst in neutrophils and monocytes was greater in MET-supplemented cows relative to CON cows. Compared with CON, PMNL adhesion and migration-related genes (ITGAM, ITGB2, ITGA4) were downregulated in response to MET and CHOL. Expression of CADM1 and SELL was also lower in MET-supplemented cows compared with CON cows but not in CHOL cows. In contrast, compared with CON cows, the expression of ICAM1 was lower in CHOL but not MET cows. Similar to adhesion and migration-related genes, cows receiving MET- or CHOL-supplemented diets had lower expression of inflammation-related genes (IL1ß, IL10RA, NFKB1, STAT3, TLR2). However, expression of IRAK1 and TLR4 was lower in MET- but not CHOL-supplemented cows. Plasma taurine concentration was greater in MET cows compared with CHOL and CON cows, suggesting a better redox status in plasma. In agreement with plasma taurine, oxidative stress-related genes (CBS, CTH, GPX1, GSS, SOD2) in PMNL were lower in response to MET and to CHOL supply. Overall, immunometabolic gene expression profile and blood biomarker analyses suggest an overall better redox status in PMNL during the transition period in response to MET and CHOL supply. These adaptations in PMNL might be beneficial for mounting a better bactericidal response upon challenge.


Assuntos
Bovinos/fisiologia , Colina/farmacologia , Suplementos Nutricionais , Metionina/farmacologia , Animais , Biomarcadores/sangue , Bovinos/imunologia , Dieta/veterinária , Feminino , Regulação da Expressão Gênica , Inflamação/veterinária , Neutrófilos/imunologia , Estresse Oxidativo , Parto , Gravidez , Distribuição Aleatória , Rúmen/metabolismo
17.
Cell Physiol Biochem ; 49(3): 1208-1216, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30196290

RESUMO

BACKGROUND/AIMS: Because the prevalence of age-related cardiac impairment increases as the human lifespan increases, it is important to combat the effects of aging. Recently, the cardiac M3 muscarinic acetylcholine receptor (M3-mAChR) has been demonstrated to play important roles in cardiac development and in the pathogenesis of cardiac diseases. However, the role of M3-mAChR in aging remains largely unknown. Therefore, the aim of this study was to investigate the involvement of M3-mAChR in the progression of cardiac aging. METHODS: We established a cardiac aging model in mice through subcutaneous injection with D-galactose at a dose of 100 mg/kg/day for 6 weeks. D-galactose was also used to induce aging in primary cultured neonatal mouse cardiomyocytes. The myocardium from mice was stained with hematoxylin and eosin for histological analysis. The protein expression levels of p53 and p21 were determined using western blotting. The mRNA and protein expression levels of M3-mAChR, caspase-1, and interleukin (IL)-1ß were determined using real-time PCR, immunohistochemical staining, and western blotting. RESULTS: The expression of M3-mAChR was down-regulated in the myocardium from aged mice and D-galactose-treated mice, while the expression levels of caspase-1 and its downstream molecule IL-1ß were significantly increased. The M3-mAChR agonist choline reduced the increase in caspase-1 in cardiomyocytes induced by D-galactose, which was reversed by the M3-mAChR antagonist 4-DAMP. Moreover, 4-DAMP promoted D-galactose-induced cardiomyocyte aging, which was attenuated by a caspase-1 inhibitor. CONCLUSION: Activation of M3-mAChR delayed cardiac aging by inhibiting the caspase-1/IL-1ß signaling pathway.


Assuntos
Caspase 1/metabolismo , Interleucina-1beta/metabolismo , Miocárdio/metabolismo , Receptor Muscarínico M3/metabolismo , Envelhecimento , Animais , Células Cultivadas , Colina/farmacologia , Regulação para Baixo/efeitos dos fármacos , Galactose/farmacologia , Camundongos , Modelos Animais , Miocárdio/patologia , Miócitos Cardíacos/citologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Transdução de Sinais/efeitos dos fármacos
18.
Mediators Inflamm ; 2018: 1312626, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30116142

RESUMO

DNA methylation has been suggested as a regulatory mechanism behind some inflammatory processes. The physiological actions of methyl donors, such as folic acid, choline, and vitamin B12 on inflammation-related disease have been associated with the synthesis of the universal methyl donor S-adenosyl methionine (SAM). The aim of this study was to evaluate the effects of folic acid, choline, vitamin B12, and a combination of all on preventing the lipopolysaccharide- (LPS-) induced inflammatory response in human THP-1 monocyte/macrophage cells. Folic acid and the mixture of methyl donors reduced interleukin 1 beta (IL1B) and tumour necrosis factor (TNF) expression as well as protein secretion by these cells. Folic acid and choline decreased C-C motif chemokine ligand 2 (CCL2) mRNA levels. In addition to this, the methyl donor mixture reduced Cluster of differentiation 40 (CD40) expression, but increased serpin family E member 1 (SERPINE1) expression. All methyl donors increased methylation levels in CpGs located in IL1B, SERPINE1, and interleukin 18 (IL18) genes. However, TNF methylation was not modified. After treatment with folic acid and the methyl donor mixture, ChIP analysis showed no change in the binding affinity of nuclear factor-κB (NF-κB) to IL1B and TNF promoter regions after the treatment with folic acid and the methyl donor mixture. The findings of this study suggest that folic acid might contribute to the control of chronic inflammation in inflammatory-related disease.


Assuntos
Ácido Fólico/farmacologia , Inflamação , Macrófagos/efeitos dos fármacos , Células THP-1/citologia , Sobrevivência Celular , Colina/farmacologia , Ilhas de CpG , Metilação de DNA , Ensaio de Imunoadsorção Enzimática , Humanos , Lipopolissacarídeos , Macrófagos/metabolismo , NF-kappa B/metabolismo , Regiões Promotoras Genéticas , Ligação Proteica , Vitamina B 12/farmacologia
19.
Nat Med ; 24(9): 1407-1417, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30082863

RESUMO

Trimethylamine N-oxide (TMAO) is a gut microbiota-derived metabolite that enhances both platelet responsiveness and in vivo thrombosis potential in animal models, and TMAO plasma levels predict incident atherothrombotic event risks in human clinical studies. TMAO is formed by gut microbe-dependent metabolism of trimethylamine (TMA) moiety-containing nutrients, which are abundant in a Western diet. Here, using a mechanism-based inhibitor approach targeting a major microbial TMA-generating enzyme pair, CutC and CutD (CutC/D), we developed inhibitors that are potent, time-dependent, and irreversible and that do not affect commensal viability. In animal models, a single oral dose of a CutC/D inhibitor significantly reduced plasma TMAO levels for up to 3 d and rescued diet-induced enhanced platelet responsiveness and thrombus formation, without observable toxicity or increased bleeding risk. The inhibitor selectively accumulated within intestinal microbes to millimolar levels, a concentration over 1-million-fold higher than needed for a therapeutic effect. These studies reveal that mechanism-based inhibition of gut microbial TMA and TMAO production reduces thrombosis potential, a critical adverse complication in heart disease. They also offer a generalizable approach for the selective nonlethal targeting of gut microbial enzymes linked to host disease limiting systemic exposure of the inhibitor in the host.


Assuntos
Microbioma Gastrointestinal , Trombose/microbiologia , Animais , Bactérias/efeitos dos fármacos , Bactérias/metabolismo , Colina/farmacologia , Dieta , Microbioma Gastrointestinal/efeitos dos fármacos , Hexanóis/farmacologia , Camundongos Endogâmicos C57BL , Oxirredutases N-Desmetilantes/antagonistas & inibidores , Oxirredutases N-Desmetilantes/metabolismo , Agregação Plaquetária/efeitos dos fármacos
20.
Radiol Med ; 123(12): 952-965, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30116970

RESUMO

Positron emission tomography (PET) has been commonly and successfully used, in combination with computed tomography (CT) and more recently magnetic resonance (MRI), in the workup of intermediate or high-risk prostate cancer (PCa). Nowadays, new specific receptor targeted PET tracers in prostate cancer imaging have been introduced; one of the most used is 68Ga-PSMA, that evaluates the expression of prostate-specific membrane antigen (PSMA). This tracer has been rapidly taken into account for its better sensitivity and specificity compared to lipid metabolism tracers, such as 11C/18F labelled fluorocholine. Besides, in the era of theranostics, this tracer is having a useful application not only for imaging but also for therapeutic purposes. The aim of this review article is, in the first part, to give an overview of the main indications and future development of 68Ga-PSMA imaging, using PET/CT or PET/MRI, according to the clinical course of the disease and in view of the current use of multiparametric MRI (mpMRI) and choline PET in the management of PCa. In the second part, a brief overview of the promising 18F-labelled PSMA tracers and the current use of PSMA radionuclide therapy will be provided.


Assuntos
Imagem por Ressonância Magnética/métodos , Imagem Multimodal , Tomografia por Emissão de Pósitrons/métodos , Antígeno Prostático Específico/análise , Neoplasias da Próstata/diagnóstico por imagem , Colina/farmacologia , Radioisótopos de Gálio/farmacologia , Humanos , Biópsia Guiada por Imagem , Masculino , Recidiva Local de Neoplasia/diagnóstico por imagem , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Compostos Radiofarmacêuticos/farmacologia , Terapia de Salvação
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