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1.
Pulm Circ ; 13(4): e12306, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37927611

RESUMO

We aimed to follow a nationwide cohort of patients with pulmonary embolism (PE) without any exclusions to generate information regarding long-term symptoms, investigational findings and to determine the prevalence of chronic thromboembolic pulmonary hypertension (CTEPH). We hypothesized that this approach would yield generalizable estimates of CTEPH prevalence and incidence. All individuals diagnosed with acute PE in Sweden in 2005 were identified using the National Patient Register. In 2007, survivors were asked to complete a questionnaire regarding current symptoms. Those with dyspnea were referred for further examinations with laboratory tests, electrocardiogram (ECG), and a ventilation/perfusion scan (V/Q scan). If CTEPH was suspected, a referral to the nearest pulmonary arterial hypertension-center was recommended. Of 5793 unique individuals with PE diagnosis in 2005, 3510 were alive at the beginning of 2007. Altogether 53% reported dyspnea at some degree whereof a large proportion had V/Q scans indicating mismatched defects. Further investigation revealed 6 cases of CTEPH and in parallel 18 cases were diagnosed outside this study. The overall prevalence of CTEPH was 0.4% (95% confidence interval [CI]: 0.2%-0.6%) and 0.7% (95% CI: 0.4%-1.0%) among the survivors. The cumulative incidence of CTEPH in the group of patients who underwent a V/Q scan was 1.1% (95% CI: 0.2%-2.0%). There was a high mortality following an acute PE, a high proportion of persistent dyspnea among survivors, whereof several had pathological findings on V/Q scans and echocardiography. Only a minority developed CTEPH, indicating that CTEPH is the tip of the iceberg of post-PE disturbances.

2.
Carbohydr Polym ; 308: 120649, 2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-36813341

RESUMO

Heparin, a major anticoagulant drug, comprises a complex mixture of motifs. Heparin is isolated from natural sources while being subjected to a variety of conditions but the detailed effects of these on heparin structure have not been studied in depth. Therefore, the result of exposing heparin to a range of buffered environments, ranging pH values from 7 to 12, and temperatures of 40, 60 and 80 °C were examined. There was no evidence of significant N-desulfation or 6-O-desulfation in glucosamine residues, nor of chain scission, however, stereochemical re-arrangement of α-L-iduronate 2-O-sulfate to α-L-galacturonate residues occurred in 0.1 M phosphate buffer at pH 12/80 °C. The results confirm the relative stability of heparin in environments like those during extraction and purification processes; on the other hand, the sensitivity of heparin to pH 12 in buffered solution at high temperature is highlighted, providing an important insight for heparin manufacturers.


Assuntos
Heparina , Sulfatos , Heparina/química , Ácido Idurônico , Fosfatos
3.
Acta Biomater ; 157: 149-161, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36526241

RESUMO

Enzyme-responsive hydrogels, formed by step growth photopolymerization of biscysteine peptide linkers with alkene functionalized polyethylene glycol, provide interesting opportunities as biomaterials and drug delivery systems. In this study, we developed stimuli-responsive, specific, and cytocompatible hydrogels for delivery of anti-inflammatory drugs for the treatment of inflammatory skin diseases. We designed peptide linkers with optimized sensitivity towards matrix metalloproteinases, a family of proteolytic enzymes overexpressed in the extracellular matrix of the skin during inflammation. The peptide linkers were crosslinked with branched 4-arm and 8-arm polyethylene glycols by thiol-norbornene photopolymerization, leading to the formation of a hydrogel network, in which the anti-inflammatory Janus kinase inhibitor tofacitinib citrate was incorporated. The hydrogels were extensively characterized by physical properties, in vitro release studies, cytocompatibility with fibroblasts, and anti-inflammatory efficacy testing in both an atopic dermatitis-like keratinocyte assay and an activated T-cell assay. The drug release was studied after single and multiple-time exposure to matrix metalloproteinase 9 to mimic inflammatory flare-ups. Drug release was found to be triggered by matrix metalloproteinase 9 and to depend on type of crosslinker and of the polyethylene glycol polymer, due to differences in architecture and swelling behavior. Moreover, swollen hydrogels showed elastic properties similar to those of extracellular matrix proteins in the dermis. Cell studies revealed limited cytotoxicity when fibroblasts and keratinocytes were exposed to the hydrogels or their enzymatic cleavage products. Taken together, our results suggest multi-arm polyethylene glycol hydrogels as promising matrix metalloproteinase-responsive drug delivery systems, with potential in the treatment of inflammatory skin disease. STATEMENT OF SIGNIFICANCE: Smart responsive drug delivery systems such as matrix metalloproteinase-responsive hydrogels are excellent candidates for the treatment of inflammatory skin diseases including psoriasis. Their release profile can be optimized to correspond to the patient's individual disease state by tuning formulation parameters and disease-related stimuli, providing personalized treatment solutions. However, insufficient cross-linking efficiency, low matrix metalloproteinase sensitivity, and undesirable drug release kinetics remain major challenges in the development of such drug delivery systems. In this study, we address shortcomings of previous work by designing peptide linkers with optimized sensitivity towards matrix metalloproteinases and high cross-linking efficiencies. We further provide a proof-of-concept for the usability of the hydrogels in inflammatory skin conditions by employing a drug release set-up simulating inflammatory flare-ups.


Assuntos
Hidrogéis , Metaloproteinase 9 da Matriz , Humanos , Hidrogéis/farmacologia , Hidrogéis/química , Peptídeos , Metaloproteinases da Matriz/metabolismo , Materiais Biocompatíveis , Polietilenoglicóis/química
4.
Angew Chem Int Ed Engl ; 61(35): e202207137, 2022 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-35718746

RESUMO

The complexation of MgII with adenosine 5'-triphosphate (ATP) is omnipresent in biochemical energy conversion, but is difficult to interrogate directly. Here we use the spin- 1/2 ß-emitter 31 Mg to study MgII -ATP complexation in 1-ethyl-3-methylimidazolium acetate (EMIM-Ac) solutions using ß-radiation-detected nuclear magnetic resonance (ß-NMR). We demonstrate that (nuclear) spin-polarized 31 Mg, following ion-implantation from an accelerator beamline into EMIM-Ac, binds to ATP within its radioactive lifetime before depolarizing. The evolution of the spectra with solute concentration indicates that the implanted 31 Mg initially bind to the solvent acetate anions, whereafter they undergo dynamic exchange and form either a mono- (31 Mg-ATP) or di-nuclear (31 MgMg-ATP) complex. The chemical shift of 31 Mg-ATP is observed up-field of 31 MgMg-ATP, in accord with quantum chemical calculations. These observations constitute a crucial advance towards using ß-NMR to probe chemistry and biochemistry in solution.


Assuntos
Trifosfato de Adenosina , Magnésio , Trifosfato de Adenosina/química , Imidazóis , Espectroscopia de Ressonância Magnética/métodos
5.
J Hydrol (Amst) ; 609: 127778, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35711240

RESUMO

The relation between arsenic groundwater concentrations and hydrogeological processes was investigated in the proximal part of the Red River delta, Vietnam, west of the depression cone formed by the exploitation of groundwater in Hanoi. Flow paths in the Quaternary aquifers were modeled based on previously interpreted geological structure and hydrogeological data gathered during field work in 2014-2017. Sedimentary structures and simulated flow patterns were compared with the spatial distribution of the groundwater arsenic concentration. The regression of the sea in the area started 4 ka BP in the Holocene. The low tectonic subsidence rate of the Red River delta led to intensive erosion and replacement of fine grained sediments of the sea level high stand by sandy channel belts, resulting in hydraulic connections between the Pleistocene and Holocene aquifers. The Pleistocene aquifer is recharged by both regional flow paths and naturally occurring vertical recharge through Holocene sand and clay layers. Young groundwater (<40 a) in the shallow Holocene aquifer generally discharges to surface water bodies. The shallow flow system is also seasonally recharged with surface water, as indicated by δ18O enrichment of groundwater and oscillating groundwater ages in wells in the vicinity of water channels. The deeper flow system discharges into the Red River and Day River or flows parallel to the rivers, toward the sea. The overall pattern of arsenic groundwater concentrations (decreasing with increasing sediment age) is modified by groundwater flow. The arsenic contamination of the Pleistocene aquifer of the Red River delta is not only caused by the intensive groundwater abstraction in Hanoi, as reported previously, but also by the natural flow of high arsenic groundwater from Holocene to Pleistocene aquifers in areas located outside of the depression cone. Groundwater with < 50 µg L-1 arsenic is found in the Pleistocene aquifer close to the recharge zone in the mountains bordering the Red River delta and in the Holocene and Pleistocene aquifers where clay deposits were eroded. Close to the recent Red River channel, recharge of older Holocene and Pleistocene sediments occurs partially by arsenic-contaminated groundwater from the youngest Holocene aquifers, and here arsenic concentrations exceed 50 µg L-1. A high arsenic concentration is also present in the early Holocene-Pleistocene aquifer, beneath thick clay layers, indicating a limited extent of flushing and the inflow of fresh organic matter.

6.
Sci Total Environ ; 814: 152641, 2022 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-34963605

RESUMO

Arsenic (As) is highly toxic and over 100 million people living on the floodplains of Asia are exposed to excessive groundwater As. A very large spatial variability over small distances has been observed in the groundwater As concentrations. Advances in the prediction of the As distribution in aquifers would support drinking water management. The application of remote sensing of geomorphic paleo river features combined with geological, geophysical and archeological data and available groundwater As measurements may be used to predict groundwater As levels in rural areas, as shown by the example from the Red River delta, Vietnam. Groundwater in sediments deposited in the marine environment is low in As, probably due to the precipitation of As in sulfide minerals under anoxic conditions. Groundwater As levels in freshwater alluvial deposits in undisturbed floodplain areas are slightly increased and the highest As concentrations are associated with meander belts. The meander belts remain clearly visible in remote sensing and may well reflect the youngest preserved alluvial sediments. High As levels in the meander belt aquifers are probably related to the availability of highly reactive organic matter and consequent reduction of iron oxyhydroxides and As release. Furthermore, given similar hydrogeological conditions, the extent of flushing of As from the youngest alluvial sands is limited compared to the older Pleistocene sands. Even within abandoned meander belts a high spatial variability of As concentrations was observed. The younger channel belts (<1 ka BP) and old Holocene aquifers below undisturbed floodplain environments deposited during a period with high sea level host groundwater enriched in As. Low As groundwater is found in sandy channel belts deposited during the regression of the sea and in Pleistocene islands preserved within the floodplain. The decisive influence of the depositional environment of the aquifer sediments on groundwater As content is revealed.


Assuntos
Arsênio , Água Subterrânea , Poluentes Químicos da Água , Arsênio/análise , Monitoramento Ambiental , Sedimentos Geológicos , Humanos , Vietnã , Poluentes Químicos da Água/análise
7.
Pulm Circ ; 11(4): 20458940211046831, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34616546

RESUMO

Dyspnea is common after a pulmonary embolism. Often, but not always, the dyspnea can be explained by pre-existing comorbidities, and only rarely by chronic thromboembolic pulmonary hypertension (CTEPH). CTEPH is probably the extreme manifestation of a far more common condition, called the post-pulmonary embolism syndrome. The purpose of this retrospective study was to investigate the prevalence and predictors of dyspnea among Swedish patients that survived a pulmonary embolism, compared to the general population. All Swedish patients diagnosed with an acute pulmonary embolism in 2005 (n = 5793) were identified via the Swedish National Patient Registry. Patients that lived until 2007 (n = 3510) were invited to participate. Of these, 2105 patients responded to a questionnaire about dyspnea and comorbidities. Data from the general population (n = 1905) were acquired from the multinational MONItoring of trends and determinants in CArdiovascular disease health survey, conducted in 2004. Patients with pulmonary embolism had substantially higher prevalences of both exertional dyspnea (53.0% vs. 17.3%, odds ratio (OR): 5.40, 95% confidence intervals (CI): 4.61-6.32) and wake-up dyspnea (12.0% vs. 1.7%, OR: 7.7, 95% CI: 5.28-11.23) compared to control subjects. These differences remained after adjustments and were most pronounced among younger patients. The increased risk for exertional dyspnea and wake-up dyspnea remained after propensity score matching (OR (95% CI): 4.11 (3.14-5.38) and 3.44 (1.95-6.06), respectively). This population-based, nation-wide study demonstrated that self-reported dyspnea was common among patients with previous pulmonary embolism. This finding suggested that a post-pulmonary embolism syndrome might be present, which merits further investigation.

8.
J Phys Chem C Nanomater Interfaces ; 125(14): 7824-7838, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-34262634

RESUMO

Solid-state, natural-abundance 95Mo NMR experiments of four different MoS2 materials have been performed on a magnet B 0 = 19.6 T and on a new Series Connected Hybrid (SCH) magnet at 35.2 T. Employing two different 2H-MoS2 (2H phase) materials, a "pseudo-amorphous" MoS2 nano-material, and a MoS2 layer on the Al2O3 support of a hydrodesulphurization (HDS) catalyst have enabled introduction of solid-state 95Mo NMR as an important analytical tool in studies of MoS2 nano-materials. 95Mo spin-lattice relaxation time (T 1) studies of 160- and 4-layer 2H-MoS2 samples at 19.6 and 35.2 T show their relaxation rates (1/T 1) increase in proportion to B 0 2. This is in accord with chemical shift anisotropy (CSA) relaxation being the dominant T 1(95Mo) mechanism, with a large 95Mo CSA = 1025 ppm determined for all four MoS2 nano-materials. The dominant CSA mechanism suggests the MoS2 band-gap electrons are delocalized throughout the lattice-layer structures, thereby acting as a fast modulation source (ω oτc << 1) for 95Mo CSA in 2H-MoS2. A decrease in T 1(95Mo) is observed for an increase in B 0 field and for a decrease in the number of 2H-MoS2 layers. All four nano-materials exhibit identical 95Mo electric field gradient (EFG) parameters. The T 1 results account for the several failures to retrieve 95Mo spectral EFG and CSA parameters for multilayer 2H-MoS2 samples in the pioneering solid-state 95Mo NMR studies performed during the past two decades (1990-2010), because of the extremely long T 1(95Mo) = ~200-250 s observed at low B 0 (~9.4 T) used at that time. Much shorter T 1(95Mo) values are observed even at 19.6 T for the "pseudo-amorphous" and the HDS catalyst (MoS2-Al2O3 support) MoS2 nano-materials. These allowed useful solid-state 95Mo NMR spectra for these two samples to be obtained at 19.6 T in a few to < 24 h. Most importantly, this research led to observation of an impressive 95Mo MAS spectrum for an average of 1-4 thick MoS2-layers on a Al2O3 support, i.e., the first MAS NMR spectrum of a low natural-abundance, low-γ quadrupole-nucleus species layered on a catalyst support. While a huge gain in NMR sensitivity, factor ~ 60, is observed for the 95Mo MAS spectrum of the 160-layer sample at 35.2 T compared to 14.1 T, the MAS spectrum for the 4-layer sample is almost completely wiped out at 35.2 T. This unusual observation for the 4-layer sample (crumpled, rose-like and defective Mo-edge structures) is due to an increased distribution of the isotropic 95Mo shifts in the 95Mo MAS spectra at B 0 up to 35.2 T upon reduction of the number of sample layers.

9.
J Agric Food Chem ; 68(8): 2506-2515, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32013414

RESUMO

Thiol groups of cysteine (Cys) residues in proteins react with quinones, oxidation products of polyphenols, to form protein-polyphenol adducts. The aim of the present work was to quantify the amount of adduct formed between Cys residues and 4-methylcatechol (4MC) in minced beef. A Cys-4MC adduct standard was electrochemically synthesized and characterized by liquid chromatography-mass spectrometry (LC-MS) as well as NMR spectroscopy. Cys-4MC adducts were quantified after acidic hydrolysis of myofibrillar protein isolates (MPIs) and LC-MS/MS analysis of meat containing either 500 or 1500 ppm 4MC and stored at 4 °C for 7 days under a nitrogen or oxygen atmosphere. The concentrations of Cys-4MC were found to be 2.2 ± 0.3 nmol/mg MPI and 8.1 ± 0.9 nmol/mg MPI in meat containing 500 and 1500 ppm 4MC, respectively, and stored for 7 days under oxygen. The formation of the Cys-4MC adduct resulted in protein thiol loss, and ca. 62% of the thiol loss was estimated to account for the formation of the Cys-4MC adduct for meat containing 1500 ppm 4MC. Furthermore, protein polymerization increased in samples containing 4MC as evaluated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and the polymerization was found to originate from protein-polyphenol interactions as evaluated by a blotting assay with staining by nitroblue tetrazolium.


Assuntos
Cisteína/química , Guaiacol/química , Carne/análise , Fenol/química , Animais , Bovinos , Proteínas Musculares/química , Oxirredução , Quinonas/química , Espectrometria de Massas em Tandem
10.
Nat Prod Rep ; 37(7): 919-961, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31971193

RESUMO

Covering: Up to 2019Phenolic cross-links and phenolic inter-unit linkages result from the oxidative coupling of two hydroxycinnamates or two molecules of tyrosine. Free dimers of hydroxycinnamates, lignans, play important roles in plant defence. Cross-linking of bound phenolics in the plant cell wall affects cell expansion, wall strength, digestibility, degradability, and pathogen resistance. Cross-links mediated by phenolic substituents are particularly important as they confer strength to the wall via the formation of new covalent bonds, and by excluding water from it. Four biopolymer classes are known to be involved in the formation of phenolic cross-links: lignins, extensins, glucuronoarabinoxylans, and side-chains of rhamnogalacturonan-I. Lignins and extensins are ubiquitous in streptophytes whereas aromatic substituents on xylan and pectic side-chains are commonly assumed to be particular features of Poales sensu lato and core Caryophyllales, respectively. Cross-linking of phenolic moieties proceeds via radical formation, is catalyzed by peroxidases and laccases, and involves monolignols, tyrosine in extensins, and ferulate esters on xylan and pectin. Ferulate substituents, on xylan in particular, are thought to be nucleation points for lignin polymerization and are, therefore, of paramount importance to wall architecture in grasses and for the development of technology for wall disassembly, e.g. for the use of grass biomass for production of 2nd generation biofuels. This review summarizes current knowledge on the intra- and extracellular acylation of polysaccharides, and inter- and intra-molecular cross-linking of different constituents. Enzyme mediated lignan in vitro synthesis for pharmaceutical uses are covered as are industrial exploitation of mutant and transgenic approaches to control cell wall cross-linking.


Assuntos
Parede Celular/química , Fenóis/química , Plantas/química , Sequência de Carboidratos
11.
N Biotechnol ; 56: 54-62, 2020 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-31770609

RESUMO

Real-time monitoring of bioprocesses plays a key-role in modern industries, providing new information on full-scale production, thus enabling control of the process and allowing it to run at optimal conditions while minimizing waste. Monitoring of phosphates and ammonium in fermentation processes has a twofold interest: they are important nutrients for living organisms while at the same time constituting environmental nutrient pollutants, for which unnecessary use and disposal must be avoided. In this report, the possibility of simultaneous analysis of phosphates and ammonium in fermentations was verified using spectroscopy-based methods combined with chemometrics to construct calibration models. To achieve this, the models were based on synthetic samples mimicking real fermentation media, providing a dataset where the analytes were completely uncorrelated. Different at-line techniques (mid- and near- infrared spectroscopy, MIR and NIR) were evaluated for their ability to monitor quickly both analytes, in a wide range of concentrations (10-100 mM), in three media of different complexities. Partial Least Squares (PLS) models on MIR spectroscopy gave very good results, with prediction errors lower than 5 % for both analytes in all datasets. In contrast, the results for PLS models on NIR spectroscopy were inferior (prediction errors between 3 and 26 %) for both analytes, as, in the case of phosphate, it could be demonstrated that the model was based on based on indirect predictions.


Assuntos
Compostos de Amônio/análise , Fermentação , Fosfatos/análise , Compostos de Amônio/metabolismo , Calibragem , Estudos de Viabilidade , Análise dos Mínimos Quadrados , Fosfatos/metabolismo , Espectroscopia de Luz Próxima ao Infravermelho
12.
Dalton Trans ; 48(23): 8327-8339, 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31111849

RESUMO

Hg2+ and Cd2+ complexation of a short hexapeptide, Ac-DCSSCY-NH2 (DY), was studied by pH-potentiometry, UV and NMR spectroscopy and fluorimetry in aqueous solutions and the Hg2+-binding ability of the ligand was also described in an immobilized form, where the peptides were anchored to a hydrophilic resin. Hg2+ was demonstrated to form a 1 : 1 complex with the ligand even at pH = 2.0 while Cd2+ coordination by the peptide takes place only above pH ∼ 3.5. Both metal ions form bis-ligand complexes by the coordination of four Cys-thiolates at ligand excess above pH ∼ 5.5 (Cd2+) and 7.0 (Hg2+). Fluorescence studies demonstrated a Hg2+ induced concentration-dependent quenching of the Tyr fluorescence until a 1 : 1 Hg2+ : DY ratio. The fluorescence emission intensity decreases linearly with the increasing Hg2+ concentration in a range of over two orders of magnitude. The fact that this occurs even in the presence of 1.0 eq. of Cd2+ per ligand reflects a complete displacement of the latter metal ion by Hg2+ from its peptide-bound form. The immobilized peptide was also shown to bind Hg2+ very efficiently even from samples at pH = 2.0. However, the existence of lower affinity binding sites was also demonstrated by binding of more than 1.0 eq. of Hg2+ per immobilized DY molecule under Hg2+-excess conditions. Experiments performed with a mixture of four metal ions, Hg2+, Cd2+, Zn2+ and Ni2+, indicate that this molecular probe may potentially be used in Hg2+-sensing systems under acidic conditions for the measurement of µM range concentrations.

13.
Food Chem ; 289: 558-567, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-30955648

RESUMO

São Francisco River Valley (SFRV) is a wine-producing semi-arid region in Brazil. Therefore, we used a 1H NMR and UPLC-MS-based metabolomic approach coupled to chemometrics to evaluate the variability in Chenin Blanc and Syrah wines for two harvest seasons, two vine training system and six rootstocks. Overall, the secondary metabolites were influenced by the three factors studied, whereas the primary metabolites were only by the seasonality. Chenin Blanc wines made in December presented higher content of an unidentified carbohydrate. In Syrah wines, glycerol, tartaric acid, succinic acid and 2,3-butanediol were greater in December, while proline and lactic acid were more abundant in July. For training system, caffeic acid derivatives were increased in wines produced from espalier. Lyre system increased phenolic compounds, organic acids and apocarotenoids. The effect of the rootstocks was less pronounced, affecting basically caffeic acid derivatives. Thus, we expect that our results may assist the winemakers to improve the SFRV wine quality.


Assuntos
Agricultura/métodos , Espectroscopia de Ressonância Magnética/métodos , Espectrometria de Massas/métodos , Vinho/análise , Brasil , Cromatografia Líquida/métodos , Análise de Alimentos/métodos , Metabolômica/métodos , Fenóis/análise , Estações do Ano , Metabolismo Secundário , Vitis/química , Vitis/metabolismo
14.
Dalton Trans ; 47(41): 14431-14435, 2018 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-30280170

RESUMO

NMR spectra of Mg2+ ions in ionic liquids were recorded using a highly sensitive variant of NMR spectroscopy known as ß-NMR. The ß-NMR spectra of MgCl2 in EMIM-Ac and EMIM-DCA compare favourably with conventional NMR, and exhibit linewidths of ∼3 ppm, allowing for discrimination of species with oxygen and nitrogen coordination.

15.
ACS Appl Mater Interfaces ; 10(43): 36686-36692, 2018 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-30211530

RESUMO

Poly(lactic- co-glycolic acid) (PLGA) microparticles represent a promising formulation approach for providing steady pharmacokinetic/pharmacodynamic profiles of therapeutic drugs for a long period. Understanding and controlling the supramolecular structure of PLGA microparticles at a molecular level is a prerequisite for the rational design of well-controlled, reproducible sustained-release profiles. Herein, we reveal the role of PLGA molecular conformation in particle formation and drug release. The nanoscale network of PLGA microparticles spray-dried using the solvents with distinct polarities was investigated by using NMR and neutron scattering. By employing chemometric method, we further demonstrate the evolution of nanoscale networks in spray-dried PLGA microparticles upon water absorption. Our results indicate that PLGA molecules form more chain entanglements during spray drying when using the solvents with low polarity, where PLGA molecule adopts a more flexible, extended conformation, resulting in the network being more resistant to water absorption in spray-dried PLGA microparticles. This work underlines the role of PLGA molecular conformation in controlling formation and evolution of nanoscale network of spray-dried PLGA microparticles and will have important consequences in achieving customized drug release from the PLGA microparticles.


Assuntos
Nanopartículas/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Polímeros/química , Acetona/química , Sistemas de Liberação de Medicamentos , Espectroscopia de Ressonância Magnética , Metanol/química , Conformação Molecular , Nêutrons , Análise de Componente Principal , Espalhamento de Radiação , Solventes/química , Viscosidade
16.
Foods ; 7(5)2018 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-29783633

RESUMO

Intake of butyrylated starches may increase colonic butyrate supply, which can be of public health and clinical benefit by maintaining colonic health. The objective was to investigate if an organocatalytic method with tartaric acid as a catalyst could be applied to produce butyrylated products from different starch sources and to characterize their chemical structure and fermentation capability by using solid-state 13C MAS NMR (magic angle spinning nuclear magnetic resonance) spectroscopy and an in vitro fermentation model, respectively. Low-amylose and high-amylose potato starch (LAPS and HAPS) and low-amylose and high-amylose maize starch (LAMS and HAMS) were subjected to organocatalytic butyrylation. This resulted in products with an increasing degree of substitution (DS) measured by heterogenous saponification and back titration with the HCl (chemical method) depending on reaction time. NMR analysis, however, showed that the major part of the acylation was induced by tartarate (75⁻89%) and only a minor part (11⁻25%) by butyrate. Generally, the chemical method overestimated the DS by 38% to 91% compared with the DS determination by NMR. Increasing the DS appeared to lower the in vitro fermentation capability of starches independent of the starch source and, therefore, do not seem to present a feasible method to deliver more butyrate to the colon than lower DS products.

17.
J Rehabil Med ; 50(5): 465-471, 2018 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-29670997

RESUMO

OBJECTIVE: To follow up the long-term outcome in return-to-work (RTW) rate in burn-injury patients, and to determine the degree of impairment in pulmonary and muscular function and exercise tolerance. DESIGN: A prospective, longitudinal follow-up study without a control group. PATIENTS: Twenty-five burn-injury patients referred for medical-vocational rehabilitation. METHODS: Return-to-work rate was followed after completed medical-vocational rehabilitation. Pulmonary function was evaluated with spirometry, diffusing capacity and radio spirometry. Exercise capacity was determined using a bicycle ergometer. Muscle functions evaluated in the arms and legs were: isokinetic torque, isometric strength, endurance and muscular strength utilization. RESULTS: Return-to-work rate was 87%. During bicycle exercise tests the patients, on average, reached their expected workloads. The dominating lung func-tion abnormality observed on lung scintigraphy was delayed wash-out time of inhaled radioactive xenon gas, suggesting airway obstruction. All tests of shoulder-flexor and knee-extensor muscle function showed large minimum-maximum differences. Mean isometric endurance of shoulder flexors was lower than mean of references, and isokinetic knee extensor torques were slightly lower. CONCLUSION: High return-to-work rates can be achieved after burn injury requiring hospital-ward care. Despite measurable impairments in muscle strength/endurance and pulmonary function in a substantial proportion of these patients, overall normal bicycle exercise capacity was observed except for a few cases.


Assuntos
Queimaduras/reabilitação , Tolerância ao Exercício/fisiologia , Reabilitação Vocacional/métodos , Testes de Função Respiratória/tendências , Retorno ao Trabalho/tendências , Adulto , Queimaduras/mortalidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Força Muscular/fisiologia , Estudos Prospectivos , Sobreviventes , Adulto Jovem
18.
Metabolomics ; 14(7): 93, 2018 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-30830430

RESUMO

INTRODUCTION: There has been a growing interest towards creating defined mixed starter cultures for alcoholic fermentations. Previously, metabolite differences between single and mixed cultures have been explored at the endpoint of fermentations rather than during fermentations. OBJECTIVES: To create metabolic footprints of metabolites that discriminate single and mixed yeast cultures at two key time-points during mixed culture alcoholic fermentations. METHODS: 1H NMR- and GC-MS-based metabolomics was used to identify metabolites that discriminate single and mixed cultures of Lachancea thermotolerans (LT) and Saccharomyces cerevisiae (SC) during alcoholic fermentations. RESULTS: Twenty-two metabolites were found when comparing single LT and mixed cultures, including both non-volatiles (carbohydrate, amino acid and acids) and volatiles (higher alcohols, esters, ketones and aldehydes). Fifteen of these compounds were discriminatory only at the death phase initiation (T1) and fifteen were discriminatory only at the death phase termination (T2) of LT in mixed cultures. Eight metabolites were discriminatory at both T1 and T2. These results indicate that specific metabolic changes may be descriptive of different LT growth behaviors. Fifteen discriminatory metabolites were found when comparing single SC and mixed cultures. These metabolites were all volatiles, and twelve metabolites were discriminatory only at T2, indicating that LT-induced changes in volatiles occur during the death phase of LT in mixed cultures and not during their initial growth stage. CONCLUSIONS: This work provides a detailed insight into yeast metabolites that differ between single and mixed cultures, and these data may be used for understanding and eventually predicting yeast metabolic changes in wine fermentations.


Assuntos
Técnicas de Cocultura , Etanol/metabolismo , Fermentação , Metabolômica , Saccharomyces cerevisiae/citologia , Saccharomyces cerevisiae/metabolismo , Fatores de Tempo
19.
Food Res Int ; 102: 256-264, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29195947

RESUMO

Protein hydrolysates are of great interest in the food industry due to their nutritional and functional properties, but their use often implies solubilization in water and therefore hamper the use of plant proteins with inherent low water solubility. Protein solubility in water can be modified by enzymatic hydrolysis, but during this process several collateral properties of the protein hydrolysates changes. It is therefore important to determine the end-point of the process and to monitor its development. In this feasibility study, we demonstrated the potential of different spectroscopic techniques (1H NMR and IR) coupled with chemometrics analysis in monitoring the hydrolysis of five different industrial grade plant proteins by the enzyme Alcalase. Logarithmic modeling of the PCA (Principal Component Analysis) scores confirmed that they can represent a measurement of the solubilized protein material released and resulted in kinetic parameters describing the suitability of protein sources as substrates for the hydrolysis. This way, we showed that a qualitative evaluation of the degree of hydrolysis is possible using fast at-line technologies and PCA.


Assuntos
Espectroscopia de Ressonância Magnética/métodos , Proteínas de Plantas/metabolismo , Subtilisinas/metabolismo , Estudos de Viabilidade , Hidrólise , Proteínas de Plantas/química , Solubilidade , Espectrofotometria Infravermelho , Vibração
20.
Food Res Int ; 91: 140-147, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-28290318

RESUMO

The ultimate aim of this study was to apply a non-targeted chemometric analysis (principal component analysis and hierarchical clustering analysis using the heat map approach) of NMR data to investigate the variability of organic compounds in nine genotype cowpea seeds, without any complex pre-treatment. In general, both exploratory tools show that Tvu 233, CE-584, and Setentão genotypes presented higher amount mainly of raffinose and Tvu 382 presented the highest content of choline and least content of raffinose. The evaluation of the aromatic region showed the Setentão genotype with highest content of niacin/vitamin B3 whereas Tvu 382 with lowest amount. To investigate rigid and mobile components in the seeds cotyledon, 13C CP and SP/MAS solid-state NMR experiments were performed. The cotyledon of the cowpea comprised a rigid part consisting of starch as well as a soft portion made of starch, fatty acids, and protein. The variable contact time experiment suggests the presence of lipid-amylose complexes.


Assuntos
Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Valor Nutritivo , Espectroscopia de Prótons por Ressonância Magnética , Sementes/química , Vigna/química , Análise por Conglomerados , Cotilédone/química , Cotilédone/genética , Genótipo , Fenótipo , Análise de Componente Principal , Sementes/genética , Vigna/genética
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