Resumen El virus del herpes simple (VHS) produce una encefalitis necrotizante aguda, afectando típicamente al lóbulo temporal. La existencia de un fármaco antiviral específico, así como el uso de ...medicación adyuvante como la corticoterapia, han mejorado el pronóstico de las infecciones graves. El retraso en el inicio del tratamiento con aciclovir es un factor claramente relacionado con mala evolución, así como las pautas cortas de tratamiento que se han asociado con mayor riesgo de recidivas.
Hindlimb ischemia is an unmet medical need, especially for those patients unable to undergo vascular surgery. Cellular therapy, mainly through mesenchymal stromal cell (MSC) administration, may be a ...potentially attractive approach in this setting. In the current work, we aimed to assess the potential of the combination of MSCs with a proangiogenic elastin-like recombinamer (ELR)–based hydrogel in a hindlimb ischemia murine model. Human bone marrow MSCs were isolated from four healthy donors, while ELR biomaterials were genetically engineered. Hindlimb ischemia was induced through ligation of the right femoral artery, and mice were intramuscularly injected with ELR biomaterial, 0.5 × 10
6
MSCs or the combination, and also compared to untreated animals. Tissue perfusion was monitored using laser Doppler perfusion imaging. Histological analysis of hindlimbs was performed after hematoxylin and eosin staining. Immunofluorescence with anti–human mitochondria antibody was used for human MSC detection, and the biomaterial was detected by elastin staining. To analyze the capillary density, immunostaining with an anti–CD31 antibody was performed. Our results show that the injection of MSCs significantly improves tissue reperfusion from day 7 (
p
= 0.0044) to day 21 (
p
= 0.0216), similar to the infusion of MSC + ELR (
p
= 0.0038,
p
= 0.0014), without significant differences between both groups. After histological evaluation, ELR hydrogels induced minimal inflammation in the injection sites, showing biocompatibility. MSCs persisted with the biomaterial after 21 days, both
in vitro
and
in vivo
. Finally, we observed a higher blood vessel density when mice were treated with MSCs compared to control (p<0.0001), but this effect was maximized and significantly different to the remaining experimental conditions when mice were treated with the combination of MSCs and the ELR biomaterial (
p
< 0.0001). In summary, the combination of an ELR-based hydrogel with MSCs may improve the angiogenic effects of both strategies on revascularization of ischemic tissues.
The pH-responsive elastin-like polymers, (PGVGV)2−(PGEGV)−(PGVGV)2 n with n = 5, 9, 15, 30, 45, were obtained using genetic engineering and microbial protein expression. These were intended to study ...the effects of the molecular weight (MW) on the properties of their inverse temperature transition (ITT) and its dependence on pH. As a result, the transition temperature decreased and the transition enthalpy increased as the molecular weight increased, especially for the lowest MWs. More strikingly, the apparent pK a for the γ-carboxyl residue of the glutamic acid also depends on MW. The apparent pK a is lower for lower MWs. In summary, the modification in the ITT caused by changes in MW is similar to the one caused by changes in the mean polarity of the polymer as described in the literature. A reduction in the molecular weight is equivalent to a decrease in the mean hydrophobicity of the polymer.
La principal manifestación clínica del herpesvirus 6 es el exantema súbito (también conocido como roséola o sexta enfermedad) y el síndrome febril. Las manifestaciones en el sistema nervioso central ...no son infrecuentes en la infección por herpesvirus 6, y su fisiopatología no está esclarecida, pero precisan diagnóstico y tratamiento temprano para evitar secuelas potencialmente graves. Se presenta el caso de una niña inmunocompetente de 2 años con cuadro de encefalitis como complicación de infección por herpesvirus 6. Se destaca la importancia del diagnóstico oportuno a fin de instaurar un adecuado tratamiento y seguimiento para evitar complicaciones secundarias a la afectación del sistema nervioso central.
Elastin-like polypeptides in drug delivery Rodríguez-Cabello, José Carlos; Arias, Francisco Javier; Rodrigo, Matilde Alonso ...
Advanced drug delivery reviews,
02/2016, Volume:
97
Journal Article
Peer reviewed
Open access
The use of recombinant elastin-like materials, or elastin-like recombinamers (ELRs), in drug-delivery applications is reviewed in this work. Although ELRs were initially used in similar ways to ...other, more conventional kinds of polymeric carriers, their unique properties soon gave rise to systems of unparalleled functionality and efficiency, with the stimuli responsiveness of ELRs and their ability to self-assemble readily allowing the creation of advanced systems. However, their recombinant nature is likely the most important factor that has driven the current breakthrough properties of ELR-based delivery systems. Recombinant technology allows an unprecedented degree of complexity in macromolecular design and synthesis. In addition, recombinant materials easily incorporate any functional domain present in natural proteins. Therefore, ELR-based delivery systems can exhibit complex interactions with both their drug load and the tissues and cells towards which this load is directed. Selected examples, ranging from highly functional nanocarriers to macrodepots, will be presented.
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The integration of implants or medical devices into the body tissues requires of good cell–material interactions. However, most polymeric materials used for these applications lack on biological ...cues, which enhanced mid- and long-term implant failure due to weak integration with the surrounding tissue. Commonly used strategies for tissue–material integration focus on functionalization of the material surface by means of natural proteins or short peptides. However, the use of these biomolecules involves major drawbacks such as immunogenic problems and oversimplification of the constructs. Here, designed elastin-like recombinamers (ELRs) are used to enhance poly(methyl methacrylate) surface properties and compared against the use of short peptides. In this study, cell response has been analysed for different functionalization conditions in the presence and absence of a competing protein, which interferes on surface–cell interaction by unspecific adsorption on the interface. The study has shown that ELRs can induce higher rates of cell attachment and stronger cell anchorages than short peptides, being a better choice for surface functionalization.
La linfadenitis es la manifestación clínica más frecuente de la infección por micobacterias no tuberculosas en niños inmunocompetentes. Se presentan dos casos de linfadenitis por M. lentiflavum ...diagnosticados en un hospital de tercer nivel en los últimos 10 años. Se realizaron pruebas complementarias de rutina ante adenopatía persistente y se obtuvo una muestra mediante drenaje para el cultivo, que resultó positivo para este germen. Ambos pacientes recibieron tratamiento antibiótico oral durante varias semanas. El caso 1 precisó exéresis completa al quinto mes de evolución, mientras que el caso 2 presentó resolución completa de la lesión a los 4 meses. M. lentiflavum es considerado, de entre las nuevas especies de micobacterias no tuberculosas recientemente descritas, un germen emergente en nuestro medio. Posee unas características microbiológicas y clínicas especiales, diferentes del resto de las micobacterias no tuberculosas. Son pocos los casos publicados hasta la fecha desde que se describió por primera vez la infección en 1997.
Here, we described a “one-pot” synthesis of smart hybrid materials based on elastin-like recombinamers (ELRs) and gold nanoparticles. Outstandingly, the reduction of auric acid in the presence of ELR
...Glu15 gave biohybrid
Au–
Glu15. TEM analysis carried out for
Au–
Glu15 exhibited nano-sized gold crystals with diameter ranging from 2 to 11
nm. Furthermore,
Au–
Glu15 promoted the formation of linear arrangements of gold clusters in areas of low particle density. Remarkable was that analogous architectures were obtained in a control experiment carried out with
Glu15 and gold nanoparticles synthesized via a citrate reduction route. Therefore,
Glu15 promoted the formation of 2D linear arrangements of gold clusters that exhibited interparticle distances in the range from 10 to 40
nm. Notable were the branched nanostructures exhibited by
Au–
Glu15B obtained for reduced gold–ELR mixtures that exhibited a lower gold ratio. On the other hand,
Au–
Glu15 exhibited spectroscopic properties (UV–vis absorption) that could be modulated as function of pH and temperature of the environment as result of reversible aggregation–expansion of gold nanoparticles. Thereby,
Au–
Glu15 displayed remarkable features suitable for the development of stimuli responsive optical sensors and detectors for biological applications that could operate in aqueous media and under a wide range of pH’s.
Water-induced chain dynamics alterations are of paramount importance in many protein-based polymers because they determine and affect to a great extent the temperature dependence of the end ...properties. In this study, the thermal behavior of the reversible unfolding and refolding of poly(Val-Pro-Gly-Val-Gly) and poly(Val-Pro-Ala-Val-Gly) and of their concurrent dehydration and hydration processes has been studied by differential scanning calorimetry (DSC) and turbidimetry. Contrary to the good reversibility shown by poly(Val-Pro-Gly-Val-Gly), the substitution of glycine by alanine in poly(Val-Pro-Ala-Val-Gly) perturbed to a large extent the process of chain unfolding. For the latter polymer, it was found that both chain unfolding and rehydration processes take place at large undercoolings, suggesting that both events occur far from equilibrium conditions and, therefore, are strongly dominated by kinetics. In this context, the existence of an hydration excess with a kinetic rather than a thermodynamic nature is a remarkable observation. The kinetics of folding and unfolding were also studied by using an isoconversional method of kinetic analysis, i.e., the model-free Friedmand's isoconversional method. As expected, the kinetics of the solvation of nonpolar moieties for both polymers indicated a complex and multistep process. Again, poly(Val-Pro-Ala-Val-Gly) showed a quite different pattern characterized by an acute hysteresis behavior which seems to govern the hydration process for this polymer. The differences observed between both polymers have been interpreted in terms of the hindrance provided by the methyl group in alanine during temperature-induced chain dynamics.
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