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1.
Nat Commun ; 14(1): 4954, 2023 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-37587123

RESUMO

Submolecular charge distribution significantly affects the physical-chemical properties of molecules and their mutual interaction. One example is the presence of a π-electron-deficient cavity in halogen-substituted polyaromatic hydrocarbon compounds, the so-called π-holes, the existence of which was predicted theoretically, but the direct experimental observation is still missing. Here we present the resolution of the π-hole on a single molecule using the Kelvin probe force microscopy, which supports the theoretical prediction of its existence. In addition, experimental measurements supported by theoretical calculations show the importance of π-holes in the process of adsorption of molecules on solid-state surfaces. This study expands our understanding of the π-hole systems and, at the same time, opens up possibilities for studying the influence of submolecular charge distribution on the chemical properties of molecules and their mutual interaction.

2.
J Hosp Infect ; 130: 122-130, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36202186

RESUMO

BACKGROUND: Limited data are currently available on the incidence rates and risk factors for bacterial sepsis and invasive fungal infections (IFIs) among neonates and infants undergoing major surgery. AIM: To assess the incidence of bacterial sepsis and IFI, fungal colonization, risk factors for sepsis, and mortality in neonates and infants aged <3 months undergoing major surgery. METHODS: A multicentre prospective study was conducted involving 13 level-3 neonatal intensive care units in Italy, enrolling all infants aged ≤3 months undergoing major surgery. FINDINGS: From 2018 to 2021, 541 patients were enrolled. During hospitalization, 248 patients had a bacterial infection, and 23 patients had a fungal infection. Eighty-four patients were colonized by fungal strains. Overall, in-hospital mortality was 2.8%, but this was higher in infected than in uninfected infants (P = 0.034). In multivariate analysis, antibiotic exposure before surgery, ultrasound-guided or surgical placement of vascular catheters, vascular catheterization duration, and gestational age ≤28 weeks were all associated with bacterial sepsis. The risk of IFI was markedly higher in colonized infants (odds ratio (OR): 8.20; P < 0.001) and was linearly associated with the duration of vascular catheterization. Fungal colonization in infants with abdominal surgery increased the probability of IFI 11-fold (OR: 11.1; P < 0.001). CONCLUSION: Preventive strategies such as early removal of vascular catheters and the fluconazole prophylaxis should be considered to prevent bacterial and fungal sepsis in infants undergoing abdominal surgery, and even more so in those with fungal colonization.


Assuntos
Infecções Fúngicas Invasivas , Micoses , Sepse , Recém-Nascido , Lactente , Humanos , Incidência , Estudos Prospectivos , Micoses/epidemiologia , Micoses/prevenção & controle , Infecções Fúngicas Invasivas/epidemiologia , Infecções Fúngicas Invasivas/tratamento farmacológico , Fatores de Risco , Sepse/epidemiologia , Sepse/tratamento farmacológico , Antifúngicos/uso terapêutico
3.
Science ; 374(6569): 863-867, 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34762455

RESUMO

An anisotropic charge distribution on individual atoms, such as σ-holes, may strongly affect the material and structural properties of systems. However, the spatial resolution of such anisotropic charge distributions on an atom represents a long-standing experimental challenge. In particular, the existence of the σ-hole on halogen atoms has been demonstrated only indirectly through the determination of the crystal structures of organic molecules containing halogens or with theoretical calculations, consequently calling for its direct experimental visualization. We show that Kelvin probe force microscopy with a properly functionalized probe can image the anisotropic charge of the σ-hole and the quadrupolar charge of a carbon monoxide molecule. This opens a new way to characterize biological and chemical systems in which anisotropic atomic charges play a decisive role.

4.
Rev. esp. cir. ortop. traumatol. (Ed. impr.) ; 63(2): 95-103, mar.-abr. 2019. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-188891

RESUMO

Objetivos: Valorar el comportamiento histológico, en un modelo animal de conejo, de un nuevo cemento óseo modificado, el cual aumenta la liberación local de antibiótico, en la infección ósea. Material y métodos: Se han utilizado 16 conejos Nueva Zelanda divididos en 4 grupos, en función del cemento (comercial o experimental) y del antibiótico (vancomicina o linezolid) empleados para controlar una infección ósea por Staphylococcus aureus. El cemento comercial es Palacos(R) R y el cemento experimental se ha conseguido añadiendo PLGA a la fase sólida del cemento Palacos(R) R. Se ha empleado un método de estadificación histológica novedoso, basado en la histoarquitectura ósea. Esta estadificación nos permite tener una visión global de la capacidad de reparación ósea, en presencia del cemento modificado, así como correlacionar el daño generado con la funcionalidad del tejido. Resultados: El grado de desestructuración ósea encontrado depende del tipo de cemento y del antibiótico, siendo mayor en los grupos con cemento comercial respecto al experimental (p<0,01) y en los grupos con linezolid respecto a vancomicina (p=0,04). El porcentaje de macrófagos varía exclusivamente en función del antibiótico utilizado, siendo mayor en los grupos con vancomicina respecto a linezolid (p=0,04). Discusión: El desarrollo de nuevas formulaciones de cemento óseo que liberan mayor cantidad, y de forma más prolongada, de antibióticos de nueva generación como el linezolid presentan un comportamiento in vivo superior al cemento comercial, respetando más la estructura ósea. Este comportamiento tendría una implicación clínica para combatir las infecciones por gérmenes cada vez más resistentes y prevenir la colonización de los espaciadores de cemento usados habitualmente en el tratamiento de la infección protésica


Objectives: To evaluate the in vivo behaviour of a new bone cement loaded with antibiotics, in a rabbit bone infection model. Material and methods: Sixteen New Zealand rabbits divided into 4 groups were used, depending on the cement (commercial or experimental) and the antibiotic (vancomycin or linezolid) used to control a bone infection caused by Staphylococcus aureus. The commercial cement is Palacos(R) R and the experimental cement has been achieved by adding PLGA to the solid phase of Palacos(R) R cement. A novel histological staging method based on bone histoarchitecture has been used. This staging allows us a global vision of bone repair capacity, in the presence of modified cement, and also allows us to correlate the damage generated with the functionality of the tissue. Results: The degree of bone destructuration found depended on the type of cement and antibiotic, and was higher in the groups with commercial cement than in the experimental group (P<.01) and in the groups with linezolid with respect to vancomycin (P=.04) The percentage of macrophages varied exclusively depending on the antibiotic used, and was higher in the vancomycin groups (P=.04). Discussion: The development of new formulations of bone cement that release more, and more prolonged, new generation antibiotics such as linezolid, present an in vivo behaviour superior to commercial cement, respecting the bone structure. This behaviour would have a clinical implication in fighting infections by increasingly resistant germs in the treatment of prosthetic infection


Assuntos
Humanos , Masculino , Feminino , Idoso , Análise de Elementos Finitos , Fraturas do Quadril/patologia , Modelos Teóricos , Cadáver
5.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-30611707

RESUMO

OBJECTIVES: To evaluate the in vivo behaviour of a new bone cement loaded with antibiotics, in a rabbit bone infection model. MATERIAL AND METHODS: Sixteen New Zealand rabbits divided into 4 groups were used, depending on the cement (commercial or experimental) and the antibiotic (vancomycin or linezolid) used to control a bone infection caused by Staphylococcus aureus. The commercial cement is Palacos® R and the experimental cement has been achieved by adding PLGA to the solid phase of Palacos® R cement. A novel histological staging method based on bone histoarchitecture has been used. This staging allows us a global vision of bone repair capacity, in the presence of modified cement, and also allows us to correlate the damage generated with the functionality of the tissue. RESULTS: The degree of bone destructuration found depended on the type of cement and antibiotic, and was higher in the groups with commercial cement than in the experimental group (P<.01) and in the groups with linezolid with respect to vancomycin (P=.04) The percentage of macrophages varied exclusively depending on the antibiotic used, and was higher in the vancomycin groups (P=.04). DISCUSSION: The development of new formulations of bone cement that release more, and more prolonged, new generation antibiotics such as linezolid, present an in vivo behaviour superior to commercial cement, respecting the bone structure. This behaviour would have a clinical implication in fighting infections by increasingly resistant germs in the treatment of prosthetic infection.


Assuntos
Antibacterianos/administração & dosagem , Cimentos Ósseos , Linezolida/administração & dosagem , Osteomielite/tratamento farmacológico , Osteomielite/microbiologia , Infecções Estafilocócicas/tratamento farmacológico , Vancomicina/administração & dosagem , Animais , Modelos Animais de Doenças , Coelhos
6.
Rev. chil. enferm. respir ; 34(2): 89-94, ago. 2018. tab
Artigo em Espanhol | LILACS | ID: biblio-959412

RESUMO

RESUMEN Objetivo: Evaluar el efecto de un dispositivo binivel autoajustable sobre los eventos respiratorios en pacientes adultos con síndrome de apnea obstructiva del sueño (SAOS) grave. Se revisaron las polisomnografías (PSG) realizadas con el uso de un dispositivo de binivel autoajustable. La arquitectura de sueño, eventos respiratorios, saturación de O2 (SpO2) y dióxido de carbono exhalado (EtCO2) se compararon entre la PSG basal y la PSG terapéutica. Resultados: Se incluyeron 10 PSG. El dispositivo binivel autoajustable corrigió la arquitectura de sueño; disminuyó el índice de apnea hipopnea (IAH) de 76 (39-137) a 14 (6-13) a expensas de apneas obstructivas y mixtas (p < 0,05), no se observó descenso significativo en las hipopneas. Las apneas centrales incrementaron de 0,5 (0-12,4) a 8,2 (0-20) h−1. La SpO2 y EtCO2 mejoraron. Conclusiones: En pacientes con SAOS grave el dispositivo binivel autoajustable corrige la arquitectura de sueño, mejora la SpO2 y EtCO2 y disminuye el IAH a expensas de apneas obstructivas y mixtas, pero podría no eliminar las hipopneas e incrementar las apneas centrales.


Objective: To evaluate the effect of an auto-bilevel device on respiratory events in adults with severe obstructive sleep apnea syndrome (OSAS). Polysomnographies (PSG) with the use of auto-bilevel device were reviewed. Sleep architecture, respiratory events, O2 saturation (SpO2) and exhaled carbon dioxide (EtCO2) were compared among baseline and therapeutic PSG. Results: We included 10 PSG. Auto-bilevel device corrected the sleep architecture; the apnea hypopnea index (AHI) decreased from 76 (39-137) to 14 (6-13) at the expense of obstructive and mixed apneas (p < 0.05), there was no significant decrease in hypopneas. Central apneas increased from 0.5 (0-12.4) to 8.2 (0-20) h−1. SpO2 and EtCO2 improved. Conclusions: In severe OSAS auto-bilevel device corrects sleep architecture, improves SpO2 and EtCO2 and decreases AHI at the expense of obstructive and mixed apneas, but could not eliminate hypopneas and even could increase central apneas.


Assuntos
Humanos , Masculino , Adolescente , Adulto , Pessoa de Meia-Idade , Engenharia Biomédica/instrumentação , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/terapia , Equipamentos e Provisões , Engenharia Biomédica/métodos , Polissonografia , Pressão Positiva Contínua nas Vias Aéreas/instrumentação , Pressão Positiva Contínua nas Vias Aéreas/métodos
7.
Carbohydr Polym ; 197: 246-252, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30007610

RESUMO

Elemental composition, physical dimensions (length and apparent diameter), and crystallinity of different types of naturally colored cotton (NCCs) fibers from Peru were investigated using a CHNS organic elemental analyzer, optical microscopy and X-Ray Diffraction (XRD). Spectroscopic studies involving Fourier Transform Infrared Spectroscopy and X-Ray photoelectron spectroscopy (XPS) were conducted; and the thermal stability of cotton samples were also investigated. Results from organic elemental analyzer and XPS showed that cotton samples contain mainly carbon, oxygen and hydrogen, but darker color samples also presented nitrogen. It was also found that the white cotton sample exhibited the longest fibers whereas the darker color samples showed the shortest values in length. Interestingly, the crystallinity seems also decrease with color intensity of NCCs. Finally, the thermal stability of white cotton fibers was similar to those obtained for the NCCs.

8.
Int J Pharm ; 522(1-2): 11-20, 2017 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-28257884

RESUMO

The incidence increase of infections in patients with hip or knee implants with resistant pathogens (mainly some S. coagulase-negative and gram positive bacteria) demands advanced antibiotic loaded formulations. In this paper, we report the design of new biantibiotic acrylic bone cements for in situ delivery. They include a last generation antibiotic (daptomycin or linezolid) in combination with vancomycin and are performed based on a novel modification of the Palacos R® acrylic bone cement, which is based on two components, a liquid (methyl methacrylate) and a solid (polymeric phase). Hence, the solid component of the experimental formulations include 45wt% of microparticles of poly(D,L-lactic-co-glycolic) acid, 55wt% of poly(methyl methacrylate) beads and supplements (10wt-% each) of antibiotics. These formulations provide a selective and excellent control of the local release of antibiotics during a long time period (up to 2 months), avoiding systemic dissemination. The antimicrobial activity of the advanced spacers tested against S. aureus shows that single doses would be enough for the control of the infection. In vitro biocompatibility of cements on human osteoblasts is ensured. This paper is mainly focused on the preparation and characterization of cements and the studies of elution kinetics and bactericidal effects. Developed formulations are proposed as spacers for the treatment of infected arthroplasties, but also, they could be applied in other antibiotic devices to treat relevant bone-related infection diseases.


Assuntos
Antibacterianos/administração & dosagem , Artroplastia/efeitos adversos , Cimentos Ósseos , Infecções Relacionadas à Prótese/prevenção & controle , Antibacterianos/farmacologia , Artroplastia de Quadril/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Daptomicina/administração & dosagem , Daptomicina/farmacologia , Combinação de Medicamentos , Composição de Medicamentos , Humanos , Linezolida/administração & dosagem , Linezolida/farmacologia , Teste de Materiais , Testes de Sensibilidade Microbiana , Microesferas , Staphylococcus aureus/efeitos dos fármacos , Vancomicina/administração & dosagem , Vancomicina/farmacologia
9.
Nanoscale ; 9(8): 2768-2777, 2017 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-28155926

RESUMO

In bio-imaging by electron microscopy, damage of the sample and limited contrast are the two main hurdles for reaching high image quality. We extend a new preparation method based on nanofabrication and super-hydrophobicity to the imaging and structural studies of nucleic acids, nucleic acid-protein complexes (DNA/Rad51 repair protein complex) and neuronal ion channels (gap-junction, K+ and GABAA channels) as paradigms of biological significance and increasing complexity. The preparation method is based on the liquid phase and is compatible with physiological conditions. Only in the very last stage, samples are dried for TEM analysis. Conventional TEM and high-resolution TEM (HRTEM) were used to achieve a resolution of 3.3 and 1.5 Å, respectively. The EM dataset quality allows the determination of relevant structural and metrological information on the DNA structure, DNA-protein interactions and ion channels, allowing the identification of specific macromolecules and their structure.


Assuntos
DNA/ultraestrutura , Canais Iônicos/ultraestrutura , Microscopia Eletrônica de Transmissão , Ácidos Nucleicos/ultraestrutura , Animais , Bicamadas Lipídicas , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/ultraestrutura , Rad51 Recombinase/ultraestrutura
10.
Phys Rev Lett ; 116(24): 245502, 2016 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-27367394

RESUMO

We show that noncontact atomic force microscopy (AFM) is sensitive to the local stiffness in the atomic-scale limit on weakly coupled 2D materials, as graphene on metals. Our large amplitude AFM topography and dissipation images under ultrahigh vacuum and low temperature resolve the atomic and moiré patterns in graphene on Pt(111), despite its extremely low geometric corrugation. The imaging mechanisms are identified with a multiscale model based on density-functional theory calculations, where the energy cost of global and local deformations of graphene competes with short-range chemical and long-range van der Waals interactions. Atomic contrast is related with short-range tip-sample interactions, while the dissipation can be understood in terms of global deformations in the weakly coupled graphene layer. Remarkably, the observed moiré modulation is linked with the subtle variations of the local interplanar graphene-substrate interaction, opening a new route to explore the local mechanical properties of 2D materials at the atomic scale.

11.
Nanotechnology ; 26(28): 285301, 2015 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-26120077

RESUMO

In this paper, we report on a method to reduce thin films of graphene oxide (GO) to a spatial resolution better than 100 nm over several tens of micrometers by means of an electrochemical scanning probe based lithography. In situ tip-current measurements show that an edged drop in electrical resistance characterizes the reduced areas, and that the reduction process is, to a good approximation, proportional to the applied bias between the onset voltage and the saturation thresholds. An atomic force microscope (AFM) quantifies the drop of the surface height for the reduced profile due to the loss of oxygen. Complementarily, lateral force microscopy reveals a homogeneous friction coefficient of the reduced regions that is remarkably lower than that of native graphene oxide, confirming a chemical change in the patterned region. Micro Raman spectroscopy, which provides access to insights into the chemical process, allows one to quantify the restoration and de-oxidation of the graphitic network driven by the electrochemical reduction and to determine characteristic length scales. It also confirms the homogeneity of the process over wide areas. The results shown were obtained from accurate analysis of the shift, intensity and width of Raman peaks for the main vibrational bands of GO and reduced graphene oxide (rGO) mapped over large areas. Concerning multilayered GO thin films obtained by drop-casting we have demonstrated an unprecedented lateral resolution in ambient conditions as well as an improved control, characterization and understanding of the reduction process occurring in GO randomly folded multilayers, useful for large-scale processing of graphene-based material.

12.
Amino Acids ; 46(11): 2561-71, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25100358

RESUMO

Cathelicidins are phylogenetically ancient, pleiotropic host defense peptides-also called antimicrobial peptides (AMPs)-expressed in numerous life forms for innate immunity. Since even the jawless hagfish expresses cathelicidins, these genetically encoded host defense peptides are at least 400 million years old. More recently, cathelicidins with varying antipathogenic activities and cytotoxicities were discovered in the venoms of poisonous snakes; for these creatures, cathelicidins may also serve as weapons against prey and predators, as well as for innate immunity. We report herein the expression of orthologous cathelicidin genes in the venoms of four different South American pit vipers (Bothrops atrox, Bothrops lutzi, Crotalus durissus terrificus, and Lachesis muta rhombeata)-distant relatives of Asian cobras and kraits, previously shown to express cathelicidins-and an elapid, Pseudonaja textilis. We identified six novel, genetically encoded peptides: four from pit vipers, collectively named vipericidins, and two from the elapid. These new venom-derived cathelicidins exhibited potent killing activity against a number of bacterial strains (S. pyogenes, A. baumannii, E. faecalis, S. aureus, E. coli, K. pneumoniae, and P. aeruginosa), mostly with relatively less potent hemolysis, indicating their possible usefulness as lead structures for the development of new anti-infective agents. It is worth noting that these South American snake venom peptides are comparable in cytotoxicity (e.g., hemolysis) to human cathelicidin LL-37, and much lower than other membrane-active peptides such as mastoparan 7 and melittin from bee venom. Overall, the excellent bactericidal profile of vipericidins suggests they are a promising template for the development of broad-spectrum peptide antibiotics.


Assuntos
Peptídeos Catiônicos Antimicrobianos/química , Bothrops/metabolismo , Peptídeos/química , Peçonhas/química , Animais , Anti-Infecciosos/química , Bactérias/efeitos dos fármacos , Hemólise , Humanos , Imunidade Inata , Peptídeos e Proteínas de Sinalização Intercelular , Meliteno/química , Especificidade da Espécie , Venenos de Vespas/química , Catelicidinas
13.
Nanotechnology ; 25(12): 125702, 2014 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-24572071

RESUMO

Exploiting the intrinsic photosensitivity of TiO2 nanoparticles, we demonstrated how ultraviolet (UV) pulsed laser irradiation of acrylate polymer nanocomposite solutions can separate the initial clusters of these colloidal semiconductor nanorods into clearly distinct units. From the irradiated solutions, optically clear nanocomposite films are obtained which exhibit enhanced optical properties with respect to the nanocomposites obtained without previous UV treatment.

14.
Nat Nanotechnol ; 8(11): 845-52, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24141538

RESUMO

Surface plasmon polaritons are a central concept in nanoplasmonics and have been exploited to develop ultrasensitive chemical detection platforms, as well as imaging and spectroscopic techniques at the nanoscale. Surface plasmons can decay to form highly energetic (or hot) electrons in a process that is usually thought to be parasitic for applications, because it limits the lifetime and propagation length of surface plasmons and therefore has an adverse influence on the functionality of nanoplasmonic devices. Recently, however, it has been shown that hot electrons produced by surface plasmon decay can be harnessed to produce useful work in photodetection, catalysis and solar energy conversion. Nevertheless, the surface-plasmon-to-hot-electron conversion efficiency has been below 1% in all cases. Here we show that adiabatic focusing of surface plasmons on a Schottky diode-terminated tapered tip of nanoscale dimensions allows for a plasmon-to-hot-electron conversion efficiency of ∼30%. We further demonstrate that, with such high efficiency, hot electrons can be used for a new nanoscopy technique based on an atomic force microscopy set-up. We show that this hot-electron nanoscopy preserves the chemical sensitivity of the scanned surface and has a spatial resolution below 50 nm, with margins for improvement.

15.
Nanotechnology ; 24(32): 325104, 2013 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-23868095

RESUMO

Traditional dynamic modalities for atomic force microscopy imaging suffer from a stringent trade-off between fast scanning speed, weak interaction forces and accurate topography reconstruction. Finding an effective compromise between these aspects is often challenging, especially for soft biological samples for which stringent requirements hold when imaged in vivo. In this paper the main causes of this undesired trade-off in standard systems are analyzed and the exploitation of the intrinsic dynamics of the cantilever through a nonlinear control strategy is proposed as a method to overcome this limitation. A direct application to imaging of biological samples is reported to validate the results and show the effectiveness of the proposed technique.

16.
Bioconjug Chem ; 24(4): 578-85, 2013 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-23458489

RESUMO

Multimeric presentation, a well-proven way of enhancing peptide immunogenicity, has found substantial application in synthetic vaccine design. We have reported that a combination of four copies of a B-cell epitope with one of a T-cell epitope in a single branched construct results in a peptide vaccine conferring total protection against foot-and-mouth disease virus in swine, a natural host (Cubillos et al. (2008) J. Virol. 82, 7223-7230). More recently, a downsized version of this prototype with only two copies of the B epitope has proven as effective as the tetravalent one in mice. Here we evaluate three approaches to bivalent platforms of this latter type, involving different chemistries for the conjugation of two B epitope peptides to a branching T epitope. Comparison of classical thioether, "reverse" thioether (Monsó et al. (2012) Org. Biomol. Chem. 10, 3116-3121) and thiol-ene conjugation chemistries in terms of synthetic efficiency clearly singles out the latter, maleimide-based strategy as most advantageous. We also examine how minor structural differences among the conjugates--including the N- or C-terminal attachment of the B epitope to the branching T epitope--bear on the immunogenicity of these vaccine candidates, with the maleimide-based conjugate again emerging as the most successful.


Assuntos
Epitopos de Linfócito B/química , Epitopos de Linfócito B/imunologia , Peptídeos/química , Peptídeos/imunologia , Animais , Reações Antígeno-Anticorpo/imunologia , Antígenos Virais/química , Antígenos Virais/imunologia , Epitopos de Linfócito T/química , Epitopos de Linfócito T/imunologia , Feminino , Camundongos , Estrutura Molecular , Peptídeos/síntese química , Vacinas Sintéticas/química , Vacinas Sintéticas/imunologia
17.
Opt Express ; 19(23): 22364-76, 2011 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-22109113

RESUMO

Optical tweezers are recognized single-molecule technique to resolve forces and motion on the molecular scale. Complex biological phenomena, such as cell differentiation and locomotion, require long range tracking capabilities with nanometer resolution over an extended period, to resolve molecular processes on the cellular scale. Here we introduce a real-time control of the microscope stage position to perform long-term tracking, with sub-millisecond resolution, of a bead attached to a neuron, preserving sub-nanometer sensitivity on a spatial range of centimeters, seven orders of magnitude larger. Moreover, the suitability of the system is tested by time- modulating the force-clamp condition to study the role of statically and dynamically applied forces in neuronal differentiation.


Assuntos
Interferometria/métodos , Pinças Ópticas , Animais , Fenômenos Biomecânicos , Calibragem , Movimento Celular , Sobrevivência Celular , Giro Denteado/citologia , Retroalimentação , Cones de Crescimento/metabolismo , Células-Tronco Neurais/citologia , Neuritos/metabolismo , Ratos , Ratos Sprague-Dawley , Fatores de Tempo
18.
Eur J Clin Microbiol Infect Dis ; 30(11): 1391-8, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21479973

RESUMO

Pan-resistant Acinetobacter baumannii have prompted the search for therapeutic alternatives. We evaluate the efficacy of four cecropin A-melittin hybrid peptides (CA-M) in vivo. Toxicity was determined in mouse erythrocytes and in mice (lethal dose parameters were LD(0), LD(50), LD(100)). Protective dose 50 (PD(50)) was determined by inoculating groups of ten mice with the minimal lethal dose of A. baumannii (BMLD) and treating with doses of each CA-M from 0.5 mg/kg to LD(0). The activity of CA-Ms against A. baumannii was assessed in a peritoneal sepsis model. Mice were sacrificed at 0 and 1, 3, 5, and 7-h post-treatment. Spleen and peritoneal fluid bacterial concentrations were measured. CA(1-8)M(1-18) was the less haemolytic on mouse erythrocytes. LD(0) (mg/kg) was 32 for CA(1-8)M(1-18), CA(1-7)M(2-9), and Oct-CA(1-7)M(2-9), and 16 for CA(1-7)M(5-9). PD(50) was not achieved with non-toxic doses (≤ LD(0)). In the sepsis model, all CA-Ms were bacteriostatic in spleen, and decreased bacterial concentration (p < 0.05) in peritoneal fluid, at 1-h post-treatment; at later times, bacterial regrowth was observed in peritoneal fluid. CA-Ms showed local short-term efficacy in the peritoneal sepsis model caused by pan-resistant Acinetobacter baumannii.


Assuntos
Infecções por Acinetobacter/tratamento farmacológico , Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Meliteno/farmacologia , Sepse/diagnóstico , Infecções por Acinetobacter/microbiologia , Infecções por Acinetobacter/mortalidade , Acinetobacter baumannii/crescimento & desenvolvimento , Animais , Antibacterianos/uso terapêutico , Peptídeos Catiônicos Antimicrobianos/uso terapêutico , Líquido Ascítico/microbiologia , Farmacorresistência Bacteriana , Eritrócitos/efeitos dos fármacos , Feminino , Humanos , Injeções Intraperitoneais , Dose Letal Mediana , Meliteno/uso terapêutico , Camundongos , Camundongos Endogâmicos C57BL , Testes de Sensibilidade Microbiana , Modelos Animais , Proteínas Recombinantes de Fusão , Sepse/microbiologia , Sepse/mortalidade , Baço/microbiologia , Fatores de Tempo
19.
Nefrologia ; 30(3): 342-8, 2010.
Artigo em Espanhol | MEDLINE | ID: mdl-20514101

RESUMO

AIM: To evaluate the prevalence of cardiovascular disease (CVD) and its association with cardiovascular risk factors, as well as their control in end-stage renal disease (ESRD) patients under maintenance hemodialysis (HD). PATIENTS AND METHODS: A total of 265 patients with ESRD on maintenance HD from a University Hospital and 4 dialysis units were included in this multicenter and cross-sectional study that analyzed the prevalence of CVD and the possible association with classic and new cardiovascular risk factors. Usual biochemical and haemathological parameters were analyzed, as well as plasma levels of homocysteine, troponin-I, BNP, lipoprotein(a), C reactive protein, IL-6, fibrinogen, asymmetrical dimethylarginine (ADMA), advanced oxidation protein products (AOPP), malondialdehyde, adiponectin, osteoprotegerin, and fetuin. In a subset of patients an echocardiography and carotid artery Doppler echography were also performed. RESULTS: The prevalence of CVD was 52.8%. Factors positively associated with prevalent CVD were age, BMI, left ventricular hypertrophy, hypertension, dyslipidemia and diabetes mellitus, dialysis vintage, Charlson s comorbility index, levels of fibrinogen, osteoprotegerin, BNP and CRP, as well as carotid intima-media thickness, left ventricular mass and pulse pressure. Factors negatively associated with prevalent CVD were: previous renal transplant, ejection fraction or levels of LDL-c and phosphorous. In the multivariate analysis dyslipidemia, left ventricular hypertrophy, age and LDL-c (negatively) were associated with CVD. CONCLUSIONS: In HD patients the prevalence of CVD is high and is associated with the presence of cardiovascular risk factors and subclinical CVD.


Assuntos
Doenças Cardiovasculares/epidemiologia , Uremia/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Arginina/análogos & derivados , Arginina/sangue , Biomarcadores , Proteínas Sanguíneas/análise , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico por imagem , Comorbidade , Estudos Transversais , Complicações do Diabetes/epidemiologia , Feminino , Humanos , Hiper-Homocisteinemia/epidemiologia , Hiperlipidemias/epidemiologia , Transplante de Rim , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Prevalência , Fatores de Risco , Fumar/epidemiologia , Volume Sistólico , Ultrassonografia , Uremia/sangue
20.
Nefrología (Madr.) ; 30(3): 342-348, mayo-jun. 2010. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-104562

RESUMO

Objetivo: Evaluar la prevalencia de ECV y su asociación con FRCV clásicos y nuevos, así como el control de los mismos en pacientes con IRCT en programa de HD. Pacientes y métodos: Se incluyeron 265 enfermos prevalentes con IRCT en HD de un hospital universitario y cuatro centros de diálisis. Estudio multicéntrico y transversal que analizó la prevalencia de ECVy su posible asociación con FRCV clásicos y nuevos. Se analizaron parámetros bioquímicos y hematológicos habituales, así como niveles de homocisteína, troponina-I, BNP, Lp(a), PCR,IL-6, fibrinógeno, ADMA, AOPP, malondialdehído, adiponectina, osteoprotegerina y fetuína. En un subgrupo de enfermos también se realizaron ecocardiografía y ecografía Doppler carotídea. Resultados: La prevalencia de ECV fue del52,8%. Los factores asociados positivamente a ECV prevalente fueron la edad, el índice de masa corporal, los antecedentes de HVI, la HTA, la dislipemia y la diabetes mellitus, el tiempo en diálisis, el índice de comorbilidad de Charlson, los niveles elevados de fibrinógeno, la osteoprotegerina, el BNPy la PCR, así como el grosor del complejo íntima-media carotídeo, la masa ventricular izquierda o la presión de pulso. Se asociaron negativamente: los antecedentes de trasplante previo, la fracción de eyección cardíaca y los niveles de cLDL ofósforo. En el análisis multivariante, los factores asociados con ECV fueron la dislipemia, la presencia de HVI, la edad y los niveles de cLDL (negativamente). Conclusiones: En los pacientes con IRCT en HD, la prevalencia de ECV es elevada y se asocia con la presencia de FRCV clásicos y ECV subclínica (AU)


Aim: To evaluate the prevalence of cardiovascular disease (CVD)and its association with cardiovascular risk factors, as well as their control in end-stage renal disease (ESRD) patients undermaintenance hemodialysis (HD). Patients and methods: A total of265 patients with ESRD on maintenance HD from a University Hospital and 4 dialysis units were included in this multicenter and cross-sectional study that analyzed the prevalence of CVD and the possible association with classic and new cardiovascular risk factors. Usual biochemical and haemathological parameters were analyzed, as well as plasma levels of homocysteine, troponin-I, BNP, lipoprotein(a), C reactive protein, IL-6,fibrinogen, asymmetrical dimethylarginine (ADMA), advanced oxidation protein products (AOPP), malondialdehyde,adiponectin, osteoprotegerin, and fetuin. In a subset of patients an echocardiography and carotid artery Doppler echography were also performed. Results: The prevalence of CVD was52.8%. Factors positively associated with prevalent CVD were age, BMI, left ventricular hypertrophy, hypertension, dyslipidemia and diabetes mellitus, dialysis vintage, Charlson´s comorbility index, levels of fibrinogen, osteoprotegerin, BNP and CRP, as well as carotid intima-media thickness, left ventricular mass and pulse pressure. Factors negatively associated with prevalent CVD were: previous renal transplant, ejection fraction or levels of LDL-c and phosphorous. In the multivariate analysis dyslipidemia, left ventricular hypertrophy, age and LDL-c (negatively) were associated with CVD. Conclusions: In HD patients the prevalence of CVD is high and is associated with the presence of cardiovascular risk factors and subclinical CVD (AU)


Assuntos
Humanos , Doenças Cardiovasculares/epidemiologia , Uremia/epidemiologia , Insuficiência Renal Crônica/epidemiologia , Fatores de Risco , Diálise Renal/métodos , Insuficiência Renal Crônica/terapia , Homocisteína/análise
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