RESUMO
One of the main pitfalls in EXAFS fitting is correlation among parameters, which can lead to unreliable fits. The use of theoretical Debye-Waller factors (DWs) is a promising way to reduce the number of fitted parameters. When working with molecular dynamics, it is not only possible to evaluate DWs from the statistical distributions issued from the trajectory but also to estimate the distribution anharmonicity, and to compute simulated average EXAFS spectra that can be fitted as experimental ones, in order to assess the ability of EXAFS fitting to recover information on DWs, as well as other structural and spectroscopical parameters. The case studied is oxaliplatin, a third generation anticancer drug. The structural information and the simulated average spectra were derived from a Car-Parrinello molecular dynamics (CP-MD) trajectory of a compound closely related to oxaliplatin. We present the DWs issued from this simulation and their use, by taking their theoretical absolute values (no DW fitted) or their ratios (one DW fitted). In this second approach, the fit of oxaliplatin experimental spectra leads to DWs values very close to the theoretical ones. This shows that the CP-MD trajectory provides a good representation of the distance distributions for oxaliplatin. Transferability of oxaliplatin DWs, for all relevant single and multiple scattering paths, to closely related compounds is proven for the case of bis(oxalato)platinum(II) and bis(ethylene diamine)platinum(II).
RESUMO
Single-atom catalysts represent an intense topic of research due to their interesting catalytic properties for a wide range of reactions. Clarifying the nature of the active sites of single-atom catalysts under realistic working conditions is of paramount importance for the design of performant materials. We have prepared an Ir single-atom catalyst supported on a nitrogen-rich carbon substrate that has proven to exhibit substantial activity toward the hydrogenation of butadiene with nearly 100% selectivity to butenes even at full conversion. We evidence here, by quantitative operando X-ray absorption spectroscopy, that the initial Ir single atoms are coordinated with four light atoms i.e., Ir-X4 (X = C/N/O) with an oxidation state of +3.2. During pre-treatment under hydrogen flow at 250 °C, the Ir atom loses one neighbour (possibly oxygen) and partially reduces to an oxidation state of around +2.0. We clearly demonstrate that Ir-X3 (X = C/N/O) is an active species with very good stability under reactive conditions. Moreover, Ir single atoms remain isolated under a reducing atmosphere at a temperature as high as 400 °C.
RESUMO
BACKGROUND: After stopping a 3 to 6 months course of oral anticoagulation for a first episode of idiopathic venous thromboembolism (VTE), the risk of recurrent VTE is high (10% per year). In this setting, international guidelines recommend at least 6 months treatment. However, this recommendation is not satisfactory for the following reasons: (1) no randomized trial has compared 6 months to extended duration (2 years) anticoagulation; and (2), even though the frequency of recurrent VTE is similar after pulmonary embolism (PE) and deep vein thrombosis (DVT), the fatality rate of recurrent VTE after PE is higher than that after DVT. METHODS: A French multicentre double blind randomized trial. The main objective is to demonstrate, after a first episode of symptomatic idiopathic PE treated for 6 months using a vitamin K antagonist, that extended anticoagulation for 18 months (INR between 2 and 3) is associated with an increased benefit / risk ratio (recurrent VTE and severe anticoagulant-related bleeding) compared to placebo. The double blind evaluation is ensured using by active warfarin and placebo, and blinded INR. The protocol was approved by the ethics board of the Brest Hospital on the 7th of March 2006. For an alpha risk of 5% and a beta risk of 20%, the estimated sample size is 374 patients. EXPECTED RESULTS: This study has the potential to: (1) demonstrate that the benefit / risk ratio of extended anticoagulation for 18 months is higher than that observed with placebo in patients with a first episode of idiopathic PE initially treated for 6 months, during and after the treatment period; and (2) to validate or invalidate the contribution of isotope lung scans, lower limb Doppler ultrasound and D-Dimer at 6 months of treatment as predictors of recurrent VTE (medico-economic analysis included).
Assuntos
Anticoagulantes/uso terapêutico , Embolia Pulmonar/tratamento farmacológico , Tromboembolia Venosa/tratamento farmacológico , Vitamina K/antagonistas & inibidores , Varfarina/uso terapêutico , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Distribuição de Qui-Quadrado , Interpretação Estatística de Dados , Método Duplo-Cego , Hemorragia/induzido quimicamente , Humanos , Placebos , Guias de Prática Clínica como Assunto , Prognóstico , Recidiva , Medição de Risco , Fatores de Tempo , Varfarina/administração & dosagem , Varfarina/efeitos adversosRESUMO
We prospectively evaluated the long-term prognosis of 14 patients with alcoholic cardiomyopathy and severe end-stage congestive heart failure after total abstinence. Improvement was very significant after 6 months of follow-up in most patients, and continued thereafter.
Assuntos
Alcoolismo/reabilitação , Cardiomiopatia Alcoólica/fisiopatologia , Insuficiência Cardíaca/fisiopatologia , Função Ventricular Esquerda/fisiologia , Adulto , Cardiomiopatia Alcoólica/diagnóstico , Progressão da Doença , Ecocardiografia , Eletrocardiografia , Seguimentos , Insuficiência Cardíaca/diagnóstico , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Volume Sistólico , gama-Glutamiltransferase/metabolismoRESUMO
A 77-year-old woman presented with chest pain and cardiogenic shock. Transesophageal echocardiography showed a mobile mass occluding intermittently the left coronary ostium. The mass was surgically resected, and histologic examination revealed an organized thrombus. Coagulation study demonstrated a protein S deficiency. This is the first case of aortic thrombosis associated with protein S deficiency, and it is the first time that transesophageal echocardiography provided definite evidence that a mass can cause intermittent left ostium coronary obstruction.
Assuntos
Valva Aórtica , Trombose Coronária/etiologia , Doenças das Valvas Cardíacas/complicações , Deficiência de Proteína S/complicações , Trombose/complicações , Idoso , Valva Aórtica/diagnóstico por imagem , Procedimentos Cirúrgicos Cardíacos , Angiografia Coronária , Trombose Coronária/diagnóstico por imagem , Trombose Coronária/cirurgia , Ecocardiografia Transesofagiana , Eletrocardiografia , Feminino , Doenças das Valvas Cardíacas/diagnóstico por imagem , Doenças das Valvas Cardíacas/cirurgia , Humanos , Proteína S/metabolismo , Deficiência de Proteína S/sangue , Trombose/diagnóstico por imagem , Trombose/cirurgiaRESUMO
A comparative study of the results of quantitative coronary angiography and endocoronary ultrasonography was performed in 37 patients undergoing percutaneous transluminal coronary angioplasty to determine the correlations between the two methods. The analyses were made before and after angioplasty at the site of stenosis and on a reference segment. A complete study before and after angioplasty using both techniques was only possible in 24 cases. The quantitative ultrasonographic analysis consisted of measurement of two orthogonal diameters, total surface area of the vessel, the endoluminal surface area and surface area of plaque. Transluminal coronary angioplasty acts mainly by forcing the plaque outwards. Ultrasonography showed a decrease in plaque area, from 10.5 +/- 6 mm2 to 9.8 +/- 5.5 mm2 and the total surface area of the vessel increased from 12.8 +/- 0.7 to 15.3 +/- 6.9 mm2 (p < 0.05). This accounted for the gain in main surface area of the stenosed lumen, from 2.28 +/- 1.28 to 5.9 +/- 2.65 mm2 (p < 0.001). The correlations between quantitative coronary angiography and ultrasonography at the site of stenosis were only significant after angioplasty both the vessel diameter (r = 0.67; p < 0.0002) and endoluminal surface area (r = 0.63; p < 0.0001). A correlation was not observed before angioplasty because of the complexity of the plaque and its excentric location. At the reference site, the correlations between ultrasonography and angiography before and after angioplasty were significant but not very close (Spearman coefficient 0.53 and 0.82 respectively, p < 0.001). Therefore, correlations between quantitative data obtained by coronary angiography and ultrasonography are modest in patients undergoing transluminal coronary angioplasty. The ultrasonographic information is more qualitative, enabling a better understanding of the mechanism of the therapeutic procedure and allowing optimal choice of the appropriate tool.
Assuntos
Angioplastia Coronária com Balão , Angiografia Coronária , Vasos Coronários/diagnóstico por imagem , Isquemia Miocárdica , Ultrassonografia de Intervenção , Adulto , Idoso , Distribuição de Qui-Quadrado , Ecocardiografia , Estudos de Avaliação como Assunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/diagnóstico por imagem , Isquemia Miocárdica/terapiaRESUMO
Between 1979 and 1996, 4 acute occlusions of the left main coronary artery (LMC) were treated by primary transluminal coronary angioplasty. They were 4 men with a mean age of 43 +/- 5 years, admitted to hospital less than 8 hours after the clinical onset of symptoms of anterior myocardial infarction in Killip class 4 with complete right bundle branch block on the initial electrocardiogramme. All cases had a previous history of unstable angina over 2 to 15 days. Angioplasty was undertaken immediately in view of the haemodynamic instability. The coronary circulation was of a dominant right coronary type in the 4 cases: significant stenoses were discovered after recanalisation, on the left anterior descending artery (LAD) in 2 cases and the circumflex or marginal arteries in 3 cases. The right coronary artery was atheromatous in all cases but without significant stenosis. Angioplasty was completed by implantation of a stent in 3 cases (LAD : 1 case, LMC : 2 cases). The outcome was rapidly fatal in 3 cases. Only one patient survived 6 months in functional class 3. These results show that myocardial infarction due to occlusion of the left main coronary artery is a very severe condition which justifies rapid recanalisation. Primary angioplasty with stent implantation in an immediate therapeutic option which enables the patient to survive the acute stage, though only in a limited number of cases.
Assuntos
Trombose Coronária/complicações , Infarto do Miocárdio/etiologia , Adulto , Angioplastia Coronária com Balão , Angiografia Coronária , Trombose Coronária/terapia , Emergências , Evolução Fatal , Seguimentos , Bloqueio Cardíaco/etiologia , Humanos , Balão Intra-Aórtico , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/terapia , Complicações Pós-Operatórias , Stents , Resultado do TratamentoRESUMO
CRYSTALFF is an alternative utility to ATOMS containing most of the features of this standard program for converting crystallographic data to FEFF input. In addition, it offers an interface with molecular modelling programs via the PDB format and new coordination sphere analysis options.
RESUMO
A combination of small angle X-ray scattering and gel techniques was used to follow the kinetics of protein crystal growth as a function of time. Hen egg white lysozyme, at different protein concentrations, was used as a model system. A new sample holder was designed, in which supersaturation is induced in the presence of salt by decreasing the temperature. It had been shown previously that a decrease in temperature and/or an increase in crystallizing agent induces an increase in the attractive interactions present in the lysozyme solutions, the lysozyme remaining monomeric. In the present paper we show that similar behaviour is observed in NaCl when agarose gels are used. During crystal growth, special attention was paid to determine whether oligomers were formed as the protein in solution was incorporated in the newly formed crystals. From these first series of experiments, we did not find any indication of oligomer formation between monomer in solution and crystal. The results obtained are in agreement with the hypothesis that lysozyme crystals in NaCl grow by addition of monomeric particles.
Assuntos
Muramidase/química , Cristalização , Proteínas do Ovo/química , Géis , Cinética , Espalhamento de Radiação , Soluções , Temperatura , Raios XRESUMO
The stability of carboplatin and oxaliplatin aqueous solutions has been studied under different chloride ions concentration and pH conditions. For both compounds, we demonstrate the chloration of the platinum first coordination shell.
Assuntos
Antineoplásicos/química , Carboplatina/química , Cloretos/química , Compostos Organoplatínicos/química , Cisplatino/química , Estabilidade de Medicamentos , Análise de Fourier , Concentração de Íons de Hidrogênio , Oxaliplatina , Soluções , Espectrometria por Raios X/métodosRESUMO
A 21 kDa protein purified from bovine brain cytosol was previously described as a hydrophobic ligand binding protein; however, its accurate biological function remained still uncertain. In order to get further information about its potential biological role, an extended prediction of its secondary and three dimensional structures was undertaken. We describe here a process which permitted us to discover a structural homology between the 21 kDa protein and the N-domain of yeast phosphoglycerate kinase (PGK). This process is based on comparing the 21 kDa protein with all the proteins presenting a slight homology, by using the Hydrophobic Cluster Analysis (HCA) method. According to the observed similarity between the N-domain of yeast PGK and the 21 kDa protein, we built a model which was shown to possess a potential binding site for nucleotides. Moreover, the model obtained presents three-dimensional (3D) structure similarity with adenylate kinase. These results suggest two main hypotheses: (i) the 21 kDa protein may belong to the kinase family; (ii) the binding of a nucleotide could imply a modification of the 3D structure of the 21 kDa protein that can promote the transfer of hydrophobic ligands to the plasma membrane. Meanwhile, verification of these hypotheses has been in part performed experimentally: the 21 kDa protein binds MgATP as well as, to a lesser extent, phosphoglycerate.
Assuntos
Proteínas do Tecido Nervoso/química , Sequência de Aminoácidos , Animais , Química Encefálica , Bovinos , Citosol/química , Modelos Moleculares , Dados de Sequência Molecular , Proteínas do Tecido Nervoso/fisiologia , Fosfoglicerato Quinase/química , Conformação Proteica , Homologia de SequênciaRESUMO
Two compounds have been designed to serve as photoaffinity reagents for use with carboxyl proteases. 1,2-Epoxy-3-(4'-azido-2'-nitrophenoxy)propane has been synthesized and shown to react with porcine pepsin in the same fashion as the traditional inhibitor 1,2-epoxy-3-(p-nitrophenoxy)propane, while p-azidophenacyl bromide is similar to other phenacyl bromides in its reaction with pepsin. In combination with p-azido-alpha-diazoacetophenone, previously shown to resemble alpha-diazo carbonyl reagents in its reaction with pepsin, photoaffinity analogs are now available for all three of the widely-used carboxyl protease inhibitors.
Assuntos
Marcadores de Afinidade/metabolismo , Endopeptidases/metabolismo , Pepsina A/metabolismo , Animais , Ácido Aspártico Endopeptidases , Azidas/metabolismo , Fotoquímica , SuínosRESUMO
[Fe(btzp)3](ClO4)2 (btzp = 1,2-bis(tetrazol-1-yl)propane) represents the first structurally characterized Fe(II) linear chain compound exhibiting thermal spin crossover. It shows a very gradual spin transition (T1/2 = 130 K) which has been followed by magnetic susceptibility measurements and 57Fe Mössbauer spectroscopy. The structure has been solved at 200 and 100 K by single-crystal X-ray analysis. It crystallizes in the trigonal space group P3c1 with Z = 2 Fe(II) units at both temperatures. The molecular structure consists of chains running along the c axis in which the Fe(II) ions are linked by three N4,N4' coordinating bis(tetrazole) ligands. The main difference between the two forms appears to be in the Fe-N bond lengths, which are 2.164(4) A at 200 K and 2.038(4) A at 100 K. The Fe-Fe separations are 7.422(1) A at 200 K and 7.273(1) A at 100 K. The EXAFS results are consistent with the crystal structure. In both spin states, the FeN6 octahedron is almost regular within the EXAFS resolution. The Fe-N distance is found as 2.16(2) A at 300 K and 2.00(2) A at 40 K. The absence of the "7 A peak" in the EXAFS spectra of [Fe(btzp)3](ClO4)2, in contrast with what has been observed for the [Fe(4-R-1,2,4-triazole)3]-(anion)2 chain compounds, confirms that this peak can be used as the signature of a metal alignment only when it involves a strongly enhanced multiple scattering M-M-M path, with M-M spacing less than 4 A. Irradiation with green light at 5 K has led to the population of the metastable high-spin state for the iron(II) ion. The nature of the spin-crossover behavior has been discussed on the basis of the structural features.