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1.
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.

2.
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
3.
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
4.
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
5.
Environ Sci Technol ; 51(2): 838-845, 2017 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-27958705

RESUMO

Recharge of Red River water into arsenic-contaminated aquifers below Hanoi was investigated. The groundwater age at 40 m depth in the aquifer underlying the river was 1.3 ± 0.8 years, determined by tritium-helium dating. This corresponds to a vertical flow rate into the aquifer of 19 m/year. Electrical conductivity and partial pressure of CO2 (PCO2) indicate that water recharged from the river is present in both the sandy Holocene and gravelly Pleistocene aquifers and is also abstracted by the pumping station. Infiltrating river water becomes anoxic in the uppermost aquifer due to the oxidation of dissolved organic carbon. Further downward, sedimentary carbon oxidation causes the reduction of As-containing Fe-oxides. Because the release of arsenic by reduction of Fe-oxides is controlled by the reaction rate, arsenic entering the solution becomes highly diluted in the high water flux and contributes little to the groundwater arsenic concentration. Instead, the As concentration in the groundwater of up to 1 µM is due to equilibrium-controlled desorption of arsenic, adsorbed to the sediment before river water started to infiltrate due to municipal pumping. Calculations indicate that it will take several decades of river water infiltration to leach arsenic from the Holocene aquifer to below the World Health Organization limit of 10 µg/L.


Assuntos
Arsênio , Rios , Monitoramento Ambiental , Água Subterrânea , Vietnã , Poluentes Químicos da Água , Abastecimento de Água
6.
Scand Cardiovasc J ; 50(4): 243-50, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27146648

RESUMO

OBJECTIVES: The Swedish Pulmonary Arterial Hypertension Register (SPAHR) is an open continuous register, including pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) patients from 2000 and onwards. We hereby launch the first data from SPAHR, defining baseline characteristics and survival of Swedish PAH and CTEPH patients. DESIGN: Incident PAH and CTEPH patients 2008-2014 from all seven Swedish PAH-centres were specifically reviewed. RESULTS: There were 457 PAH (median age: 67 years, 64% female) and 183 CTEPH (median age: 70 years, 50% female) patients, whereof 77 and 81%, respectively, were in functional class III-IV at diagnosis. Systemic hypertension, diabetes, ischaemic heart disease and atrial fibrillation were common comorbidities, particularly in those >65 years. One-, 3- and 5-year survival was 85%, 71% and 59% for PAH patients. Corresponding numbers for CTEPH patients with versus without pulmonary endarterectomy were 96%, 89% and 86% versus 91%, 75% and 69%, respectively. In 2014, the incidence of IPAH/HPAH, associated PAH and CTEPH was 5, 3 and 2 per million inhabitants and year, and the prevalence was 25, 24 and 19 per million inhabitants. CONCLUSION: The majority of the PAH and CTEPH patients were diagnosed at age >65 years, in functional class III-IV, and exhibiting several comorbidities. PAH survival in SPAHR was similar to other registers.


Assuntos
Hipertensão Pulmonar Primária Familiar , Hipertensão Pulmonar , Embolia Pulmonar/complicações , Idoso , Comorbidade , Hipertensão Pulmonar Primária Familiar/diagnóstico , Hipertensão Pulmonar Primária Familiar/epidemiologia , Feminino , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/epidemiologia , Hipertensão Pulmonar/etiologia , Incidência , Masculino , Gravidade do Paciente , Análise de Sobrevida , Suécia/epidemiologia
7.
Biochem J ; 468(3): 495-506, 2015 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-25846210

RESUMO

Class 1 cytokine receptors regulate essential biological processes through complex intracellular signalling networks. However, the structural platform for understanding their functions is currently incomplete as structure-function studies of the intracellular domains (ICDs) are critically lacking. The present study provides the first comprehensive structural characterization of any cytokine receptor ICD and demonstrates that the human prolactin (PRL) receptor (PRLR) and growth hormone receptor (GHR) ICDs are intrinsically disordered throughout their entire lengths. We show that they interact specifically with hallmark lipids of the inner plasma membrane leaflet through conserved motifs resembling immuno receptor tyrosine-based activation motifs (ITAMs). However, contrary to the observations made for ITAMs, lipid association of the PRLR and GHR ICDs was shown to be unaccompanied by changes in transient secondary structure and independent of tyrosine phosphorylation. The results of the present study provide a new structural platform for studying class 1 cytokine receptors and may implicate the membrane as an active component regulating intracellular signalling.


Assuntos
Membrana Celular/metabolismo , Modelos Moleculares , Receptores da Prolactina/metabolismo , Receptores da Somatotropina/metabolismo , Linhagem Celular , Membrana Celular/química , Dicroísmo Circular , Humanos , Interações Hidrofóbicas e Hidrofílicas , Bicamadas Lipídicas/química , Bicamadas Lipídicas/metabolismo , Ressonância Magnética Nuclear Biomolecular , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/metabolismo , Fosfatidilcolinas/química , Fosfatidilcolinas/metabolismo , Fosfatidilserinas/química , Fosfatidilserinas/metabolismo , Dobramento de Proteína , Estrutura Terciária de Proteína , Receptores da Prolactina/química , Receptores da Prolactina/genética , Receptores da Somatotropina/química , Receptores da Somatotropina/genética , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Espalhamento a Baixo Ângulo , Transdução de Sinais , Tirosina/metabolismo , Difração de Raios X
8.
Mol Pharm ; 12(11): 4067-76, 2015 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-26393273

RESUMO

The aim of this study was to investigate if molecular interactions between the weak base cinnarizine and lipolysis products were affecting the morphology of precipitated drug formed during in vitro lipolysis. In vitro lipolysis studies of a self-nanoemulsifying drug delivery system with or without cinnarizine were conducted. The digestion phases (aqueous phase and pellet phase) were separated by ultracentrifugation, and the pellet was isolated and lyophilized. The lyophilized pellets were examined by X-ray powder diffraction, (13)C solid-state nuclear magnetic resonance ((13)C NMR), (1)H liquid-state NMR ((1)H NMR) spectroscopy and differential scanning calorimetry (DSC). The (13)C NMR data indicated that the carbonyl groups and aliphatic part of the lipids undergo structural changes when the pellet contains cinnarizine. The (1)H NMR data suggests interactions occurring around the nitrogens on cinnarizine and the carboxylic group of fatty acids. DSC thermograms showed cinnarizine to be homogeneously incorporated into the lipids of the pellet, and no free amorphous cinnarizine was present. The three techniques (13)C NMR, (1)H NMR, and DSC complement each other and suggest interactions to occur between fatty acids and cinnarizine, which in turn favors amorphous precipitation.


Assuntos
Bloqueadores dos Canais de Cálcio/química , Precipitação Química , Cinarizina/química , Sistemas de Liberação de Medicamentos , Lipídeos/química , Varredura Diferencial de Calorimetria , Química Farmacêutica , Portadores de Fármacos , Lipólise , Solubilidade , Fatores de Tempo
9.
Mol Pharm ; 12(7): 2484-92, 2015 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-26057950

RESUMO

Two coamorphous drug-amino acid systems, indomethacin-tryptophan (Ind-Trp) and furosemide-tryptophan (Fur-Trp), were analyzed toward their ease of amorphization and mechanism of coamorphization during ball milling. The two mixtures were compared to the corresponding amorphization of the pure drug without amino acid. Powder blends at a 1:1 molar ratio were milled for varying times, and their physicochemical properties were investigated using XRPD, (13)C solid state NMR (ssNMR), and DSC. Comilling the drug with the amino acid reduced the milling time required to obtain an amorphous powder from more than 90 min in the case of the pure drugs to 30 min for the coamorphous powders. Amorphization was observed as reductions in XRPD reflections and was additionally quantified based on normalized principal component analysis (PCA) scores of the ssNMR spectra. Furthermore, the evolution in the glass temperature (Tg) of the coamorphous systems over time indicated complete coamorphization after 30 min of milling. Based on the DSC data it was possible to identify the formation mechanism of the two coamorphous systems. The Tg position of the samples suggested that coamorphous Ind-Trp was formed by the amino acid being dissolved in the amorphous drug, whereas coamorphous Fur-Trp was formed by the drug being dissolved in the amorphous amino acid.


Assuntos
Aminoácidos/química , Furosemida/química , Indometacina/química , Cristalização/métodos , Estabilidade de Medicamentos , Espectroscopia de Ressonância Magnética/métodos , Pós/química , Solubilidade , Temperatura , Triptofano/química , Difração de Raios X/métodos
10.
Angew Chem Int Ed Engl ; 54(52): 15756-61, 2015 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-26563985

RESUMO

Metal-ion-responsive transcriptional regulators within the MerR family effectively discriminate between mono- and divalent metal ions. Herein we address the origin of the specificity of the CueR protein for monovalent metal ions. Several spectroscopic techniques were employed to study Ag(I) , Zn(II) , and Hg(II) binding to model systems encompassing the metal-ion-binding loop of CueR from E. coli and V. cholerae. In the presence of Ag(I) , a conserved cysteine residue displays a pKa  value for deprotonation of the thiol that is close to the physiological pH value. This property is only observed with the monovalent metal ion. Quantum chemically optimized structures of the CueR metal site with Cys 112 protonated demonstrate that the conserved Ser 77 backbone carbonyl oxygen atom from the other monomer of the homodimer is "pulled" towards the metal site. A common allosteric mechanism of the metalloregulatory members of the MerR family is proposed. For CueR, the mechanism relies on the protonation of Cys 112.

11.
Chemphyschem ; 15(18): 3929-32, 2014 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-25303164

RESUMO

ß-nuclear magnetic resonance (NMR) spectroscopy is highly sensitive compared to conventional NMR spectroscopy, and may be applied for several elements across the periodic table. ß-NMR has previously been successfully applied in the fields of nuclear and solid-state physics. In this work, ß-NMR is applied, for the first time, to record an NMR spectrum for a species in solution. (31)Mg ß-NMR spectra are measured for as few as 10(7) magnesium ions in ionic liquid (EMIM-Ac) within minutes, as a prototypical test case. Resonances are observed at 3882.9 and 3887.2 kHz in an external field of 0.3 T. The key achievement of the current work is to demonstrate that ß-NMR is applicable for the analysis of species in solution, and thus represents a novel spectroscopic technique for use in general chemistry and potentially in biochemistry.


Assuntos
Magnésio/análise , Espectroscopia de Ressonância Magnética/métodos , Líquidos Iônicos/química , Radioisótopos/análise , Soluções
12.
Pharm Res ; 30(1): 280-9, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22996567

RESUMO

PURPOSE: To understand the transformation pathways amongst anhydrate/hydrate solid forms of sodium naproxen and to highlight the importance of a polymorphic dihydrate within this context. METHODS: Multi-temperature dynamic vapour sorption (DVS) analysis combined with variable-humidity X-ray powder diffraction (XRPD) to establish the transformation pathways as a function of temperature and humidity. XRPD and thermogravimetric analysis (TGA) to characterise bulk samples. Monitoring of in-situ dehydration using solid-state (13)C CP/MAS spectroscopy. RESULTS: At 25 °C, anhydrous sodium naproxen (AH) transforms directly to one dihydrate polymorph (DH-II). At 50 °C, AH transforms stepwise to a monohydrate (MH) then to the other dihydrate polymorph (DH-I). DH-II transforms to a tetrahydrate (TH) more readily than DH-I transforms to TH. Both dihydrate polymorphs transform to the same MH. CONCLUSIONS: The properties of the polymorphic dihydrate control the transformation pathways of sodium naproxen.


Assuntos
Anti-Inflamatórios não Esteroides/química , Naproxeno/química , Água/química , Cristalização , Umidade , Difração de Pó , Sódio/química , Temperatura , Termogravimetria , Difração de Raios X
13.
Analyst ; 138(7): 2096-103, 2013 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-23400050

RESUMO

A method for quantification of total soluble protein-derived thiols in beer was developed based on the formation of fluorescent adducts with the maleimide compound ThioGlo 1. The problem of interference from fluorescent adducts of sulfite and ThioGlo 1 was solved by HPLC separation of the adducts followed by fluorescence detection. Using standard addition of GSH, a detection limit of 0.028 µM thiols was achieved. The application and validation of the method was demonstrated for beers with different color intensities, and the application range is in principle for any biological system containing thiols. However, the quantification of cysteine was complicated by a lower fluorescence response of its ThioGlo 1 adducts. Based on the studies of the responses of a series of cysteine-derived thiols and (1)H NMR studies of the structures of ThioGlo 1 adducts with GSH and cysteine, it was concluded that thiols with a neighboring free amino group yield ThioGlo 1 adducts with a reduced fluorescence intensity.


Assuntos
Cerveja/análise , Proteínas/química , Compostos de Sulfidrila/análise , Cromatografia Líquida de Alta Pressão/métodos , Cisteína/química , Corantes Fluorescentes/química , Glutationa/química , Naftalenos , Ressonância Magnética Nuclear Biomolecular , Pirróis
14.
Am J Emerg Med ; 31(3): 482-6, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23154103

RESUMO

BACKGROUND: Right ventricular (RV) involvement in pulmonary embolism (PE) is an ominous sign. The aim of this study was to investigate the extent to which the d-dimer level or simplified PE severity index (sPESI) indicates RV dysfunction in patients with preserved systemic arterial pressure. METHODS: Right ventricular function was studied in 34 consecutive patients with acute nonmassive PE by echocardiography including Doppler tissue imaging within 24 hours after arrival to the hospital. d-Dimer and sPESI were assessed upon arrival. RESULTS: d-Dimer correlated with RV pressure (Rs, 0.60; P < .001) and pulmonary vascular resistance (PVR; Rs, 0.68; P < .0001) and tended to be related to myocardial performance index (MPI; Rs, 0.31; P = .067). Compared to a level less than 3.0 mg/L, patients with d-dimer 3.0 mg/L or higher had lower systolic tricuspid annular velocity (11.3 ± 2.7 vs 13.5 ± 2.7 cm/s; P < .05), a prolonged MPI (0.8 ± 0.3 vs 0.5 ± 0.2; P < .01), increased RV pressure (58 ± 13 vs 37 ± 12 mm Hg; P < .001), and increased PVR (3.3 ± 1.1 vs 1.8 ± 0.4 Woods units; P < .001). Patients in the high-risk sPESI group had higher filling pressure than those in the low risk sPESI group. CONCLUSIONS: In the acute stage of PE, a d-dimer level 3 mg/L or higher may identify nonmassive PE patients with RV dysfunction and thereby help to determine their risk profile. We found no additional value for sPESI in this context.


Assuntos
Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Embolia Pulmonar/complicações , Índice de Gravidade de Doença , Disfunção Ventricular Direita/diagnóstico , Doença Aguda , Idoso , Biomarcadores/sangue , Técnicas de Apoio para a Decisão , Ecocardiografia Doppler , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Embolia Pulmonar/sangue , Embolia Pulmonar/diagnóstico , Curva ROC , Medição de Risco , Sensibilidade e Especificidade , Disfunção Ventricular Direita/sangue , Disfunção Ventricular Direita/diagnóstico por imagem , Disfunção Ventricular Direita/etiologia
15.
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.

16.
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
17.
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
18.
Int J Mol Sci ; 13(1): 929-942, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22312295

RESUMO

Gelatinized wheat, potato and waxy maize starches were treated enzymatically in order to increase the degree of branching of the amylopectin fraction and thereby change the starch degradation profile towards a higher proportion of slowly digestible starch (SDS). The materials were characterized by single-pulse (1)H HR-MAS NMR spectroscopy and in vitro digestion profile according to the Englyst procedure. Using various concentrations and incubation times with branching enzyme (EC 2.4.1.18) without or with additional treatment with the hydrolytic enzymes; ß-amylase (EC 3.2.1.2), α-glucosidase (EC 3.2.1.20), or amyloglucosidase (EC 3.2.1.3) the proportion of α-(1-6) linkages was increased by up to a factor of 4.1, 5 and 5.8 in waxy maize, wheat and potato starches, respectively. The proportion of SDS was significantly increased when using hydrolytic enzymes after treatment with branching enzyme but it was only for waxy maize that the proportion of α-(1-6) bonds and the in vitro digestion profile was significantly correlated.


Assuntos
Amido/metabolismo , Glucana 1,4-alfa-Glucosidase/metabolismo , Hidrólise , Espectroscopia de Ressonância Magnética , Solanum tuberosum/metabolismo , Amido/química , Triticum/metabolismo , Zea mays/metabolismo , alfa-Glucosidases/metabolismo , beta-Amilase/metabolismo
19.
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
20.
Biomacromolecules ; 12(5): 1844-50, 2011 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-21462966

RESUMO

Hydration of rhamnogalacturonan-I (RG-I) derived from potato cell wall was analyzed by (13)C single-pulse (SP) magic-angle-spinning (MAS) and (13)C cross-polarization (CP) MAS nuclear magnetic resonance (NMR) and supported by (2)H SP/MAS NMR experiments. The study shows that the arabinan side chains hydrate more readily than the galactan side chains and suggests that the overall hydration properties can be controlled by modifying the ratio of these side chains. Enzymatic modification of native (NA) RG-I provided samples with reduced content of arabinan (sample DA), galactan (sample DG), or both side chains (sample DB). Results of these samples suggested that hydration properties were determined by the length and character of the side chains. NA and DA exhibited similar hydration characteristics, whereas DG and DB were difficult to hydrate because of the less hydrophilic properties of the rhamnose-galacturonic acid (Rha-GalA) backbone in RG-I. Potential food ingredient uses of RG-I by tailoring of its structure are discussed.


Assuntos
Parede Celular/química , Espectroscopia de Ressonância Magnética/métodos , Pectinas/química , Solanum tuberosum/química , Água/química , Isótopos de Carbono
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