Nanomaterials and Nanostructures Hand-In-Hand with Biology.

The nanoparticle's synthesis had its tipping point at the beginning of the 21st century, opening up the possibility of manufacturing nanoparticles with almost every imaginable shape and size [...].

SPION nanoparticles for delivery of dopaminergic isoquinoline and benzazepine derivatives.

Superparamagnetic iron nanoparticles (SPIONs) have become one of the most useful colloidal systems in nanomedicine. We report here the preparation of new hybrid core@shell systems based on SPION nanoparticles coated with a SiO2 shell (SPION@SiO2) and functionalized with carboxyl groups (SPION@SiO2-COOH). A series of new N-alkylamino- and N-alkylamido-terminated 1-phenyl- tetrahydroisoquinolines (THIQs) and 3-tetrahydrobenzazepines (THBs) derivatives presenting -SMe and -Cl groups, respectively, with potential dopaminergic activity, are synthesized and incorporated to the hybrid system. We include the synthetic details for THIQs and THBs derivatives preparation and investigate the influence of the terminal-functional group as well as the number of carbon atoms linked to THIQ and THB molecules during the coupling to the SPION@SiO2-COOH. Nuclear magnetic resonance (NMR) and electron ionization mass spectrometry (EI-MS) are used to characterize the synthesized THIQs and THBs. High-angle annular dark-field transmission electron microscopy (HAADF-TEM), energy dispersive X-ray transmission electron microscopy (EDX-TEM), and proton high-resolution magic angle spinning NMR spectroscopy1H HRMAS-NMR) are used to confirm the presence of THB and THIQ molecules onto the surface of the nanoparticles. The hybrid SPION@SiO2-THIQ and THB systems show significant activity toward the D2 receptor, reaching Ki values of about 20 nM, thus having potential application in the treatment of central nervous system (CNS) diseases.

Electrospraying as a Technique for the Controlled Synthesis of Biocompatible PLGA@Ag2S and PLGA@Ag2S@SPION Nanocarriers with Drug Release Capability.

Ag2S nanoparticles are near-infrared (NIR) probes providing emission in a specific spectral range (~1200 nm), and superparamagnetic iron oxide nanoparticles (SPION) are colloidal systems able to respond to an external magnetic field. A disadvantage of Ag2S NPs is the attenuated luminescent properties are reduced in aqueous media and human fluids. Concerning SPION, the main drawback is the generation of undesirable clusters that reduce particle stability. Here, we fabricate biocompatible hybrid nanosystems combining Ag2S NPs and SPION by the electrospraying technique for drug delivery purposes. These nanostructures are composed of poly(lactic-co-glycolic acid) (PLGA) as the polymeric matrix in connection with both Ag2S NPs and SPIONs. Initially, we fabricate a hybrid colloidal nanosystem composed of Ag2S NPs in connection with PLGA (PLGA@Ag2S) by three different routes, showing good photoluminescent (PL) properties with relatively high average decay times. Then, we incorporate SPIONs, obtaining a PLGA polymeric matrix containing both Ag2S NPs and SPION (PLGA@Ag2S@SPION). Interestingly, in this hybrid system, the location of Ag2S NPs and SPIONs depends on the synthesis route performed during electrospraying. After a detailed characterization, we demonstrate the encapsulation and release capabilities, obtaining the kinetic release using a model chemotherapeutic drug (maslinic acid). Finally, we perform in vitro cytotoxicity assays using drug-loaded hybrid systems against several tumor cell lines.

10-Fold Quantum Yield Improvement of Ag2S Nanoparticles by Fine Compositional Tuning.

Ag2S semiconductor nanoparticles (NPs) are near-infrared luminescent probes with outstanding properties (good biocompatibility, optimum spectral operation range, and easy biofunctionalization) that make them ideal probes for in vivo imaging. Ag2S NPs have, indeed, made possible amazing challenges including in vivo brain imaging and advanced diagnosis of the cardiovascular system. Despite the continuous redesign of synthesis routes, the emission quantum yield (QY) of Ag2S NPs is typically below 0.2%. This leads to a low luminescent brightness that avoids their translation into the clinics. In this work, an innovative synthetic methodology that permits a 10-fold increment in the absolute QY from 0.2 up to 2.3% is presented. Such an increment in the QY is accompanied by an enlargement of photoluminescence lifetimes from 184 to 1200 ns. The optimized synthetic route presented here is based on a fine control over both the Ag core and the Ag/S ratio within the NPs. Such control reduces the density of structural defects and decreases the nonradiative pathways. In addition, we demonstrate that the superior performance of the Ag2S NPs allows for high-contrast in vivo bioimaging.

Nanoparticles for multimodal antivascular therapeutics: Dual drug release, photothermal and photodynamic therapy.

The poor delivery of nanoparticles to target cancer cells hinders their success in the clinical setting. In this work, an alternative target readily available for circulating nanoparticles has been selected to eliminate the need for nanoparticle penetration in the tissue: the tumor blood vessels. A tumor endothelium-targeted nanoparticle (employing an RGD-containing peptide) capable of co-delivering two anti-vascular drugs (one anti-angiogenic drug and one vascular disruption agent) is here presented. Furthermore, the nanodevice presents two additional anti-vascular capabilities upon activation by Near-Infrared light: provoking local hyperthermia (by gold nanorods in the system) and generating toxic reactive oxygen species (by the presence of a photosensitizer). RGD-targeting is shown to increase uptake by HUVEC cells, and while the nanoparticles are shown not to be toxic for these cells, upon Near-Infrared irradiation their almost complete killing is achieved. The combination of all four therapeutic modalities is then evaluated in an ex ovo fibrosarcoma xenograft model, which shows a significant reduction in the number of blood vessels irrigating the xenografts when the nanoparticles are present, as well as the destruction of the existing blood vessels upon irradiation. These results suggest that the combination of different anti-vascular therapeutic strategies in a single nanocarrier appears promising and should be further explored in the future. STATEMENT OF SIGNIFICANCE MVR2019: The combination of antivascular drugs with different mechanisms of action (such as antiangiogenic drugs and vascular disruption agents) has been recently proposed as a promising approach to maximize the therapeutic potential of anti-vascular therapeutics. Given the capacity of nanoparticles to co-deliver different drugs in optimizable ratios, nanomedicine appears to have a huge potential for the development of this kind of multimodal antivascular. To showcase this, an multimodal anti-vascular nanodevice for cancer therapy is here presented. This tumor endothelium-targeted nanosystem is capable of co-delivering two anti-vascular drugs (anti-angiogenic and vascular disruption agent) while also providing two additional therapeutic modalities that can be activated by Near-Infrared light: provoking local hyperthermia (photothermal therapy) and generating toxic reactive oxygen species (photodynamic therapy).

Targeting strategies for improving the efficacy of nanomedicine in oncology.

The use of nanoparticles as drug carriers has provided a powerful weapon in the fight against cancer. These nanocarriers are able to transport drugs that exhibit very different nature such as lipophilic or hydrophilic drugs and big macromolecules as proteins or RNA. Moreover, the external surface of these carriers can be decorated with different moieties with high affinity for specific membrane receptors of the tumoral cells to direct their action specifically to the malignant cells. The selectivity improvement yielded by these nanocarriers provided a significative enhancement in the efficacy of the transported drug, while the apparition of side effects in the host was reduced. Additionally, it is possible to incorporate targeting moieties selective for organelles of the cell, which improves even more the effect of the transported agents. In the last years, more sophisticated strategies such as the use of switchable, hierarchical or double targeting strategies have been proposed for overcoming some of the limitations of conventional targeting strategies. In this review, recent advances in the development of targeted nanoparticles will be described with the aim to present the current state of the art of this technology and its huge potential in the oncological field.

Molecular Scaffolds as Double-Targeting Agents For the Diagnosis and Treatment of Neuroblastoma.

The selective delivery of therapeutic and imaging agents to tumoral cells has been postulated as one of the most important challenges in the nanomedicine field. Meta-iodobenzilguanidine (MIBG) is widely used for the diagnosis of neuroblastoma (NB) due to its strong affinity for the norepinephrine transporter (NET), usually overexpressed on the membrane of malignant cells. Herein, a family of novel Y-shaped scaffolds has been synthesized, which have structural analogues of MIBG covalently attached at each end of the Y-structure. The cellular uptake capacity of these double-targeting ligands has been evaluated in vitro and in vivo, yielding one specific Y-shaped structure that is able to be engulfed by the malignant cells, and accumulates in the tumoral tissue, at significantly higher levels than the structure containing only one single targeting agent. This Y-shaped ligand can provide a powerful tool for the current treatment and diagnosis of this disease.

From proof-of-concept material to PEGylated and modularly targeted ultrasound-responsive mesoporous silica nanoparticles.

In this work we present the synthesis, characterization and in vitro biological evaluation of PEGylated and actively-targeted ultrasound-responsive hybrid mesoporous silica nanoparticles. This work covers the development of the chemical strategies necessary to afford a modular nanocarrier starting from a proof-of-concept material presented in previous work. This functional ultrasound-responsive material can be adapted to different specific pathological conditions by carefully choosing the appropriate targeting moieties. The new ultrasound responsive material is able to target HeLa cells when conjugated with biotin or an RGD peptide. Ultrasound-responsive cytotoxicity towards cancer cells of doxorubicin-loaded nanoparticles is demonstrated in an in vitro cytotoxicity assay.

Janus Mesoporous Silica Nanoparticles for Dual Targeting of Tumor Cells and Mitochondria.

The development of targeted nanocarriers able to be selectively internalized within tumor cells, and therefore to deliver anti-tumor drugs specifically to diseased cells, constitutes one of the most important goals in nano-oncology. Herein, the development of Janus mesoporous silica particles asymmetrically decorated with two targeting moieties, one of them selective for folate membrane cell receptors (folic acid) and the other one able to bind to mitochondria membrane (triphenylphosphine, TPP), is described in order to achieve sequential cell to organelle vectorization. The asymmetric decoration of each side of the particle allows fine control in the targeting attachment process in comparison with the use of symmetric nanocarriers. The presence of folic acid induces a higher increase in particle accumulation inside tumor cells, and once there, these nanocarriers are guided close to mitochondria by the action of the TPP moiety. This strategy can be applied for improving the therapeutic efficacy of current nanomedicines.

Double Sequential Encrypted Targeting Sequence: A New Concept for Bone Cancer Treatment.

The selective transportation of therapeutic agents to tumoral cells is usually achieved by their conjugation with targeting moieties able to recognize these cells. Unfortunately, simple and static targeting systems usually show a lack in selectivity. Herein, a double sequential encrypted targeting system is proposed as a stimuli-responsive targeting analogue for selectivity enhancement. The system is able to recognize diseased bone tissue in the first place, and once there, a hidden secondary targeting group is activated by the presence of an enzyme overproduced in the malignant tissue (cathepsin K), thereby triggering the recognition of diseased cells. Transporting the cell targeting agent in a hidden conformation that contains a high selective tissular primary targeting, could avoid not only its binding to similar cell receptors but also the apparition of the binding-site barrier effect, which can enhance the penetration of the therapeutic agent within the affected zone. This strategy could be applied not only to conjugate drugs but also to drug-loaded nanocarriers to improve the efficiency for bone cancer treatments.

A new targeting agent for the selective drug delivery of nanocarriers for treating neuroblastoma.

Novel targeting agents against neuroblastoma based on the meta-iodobenzylguanidine (MIBG) moiety were synthesized and biologically evaluated for nanocarrier vectorization. These compounds have been anchored on the surface of drug loaded mesoporous silica nanocarriers, resulting in the improved cellular uptake in tumoral cells. Neuroblastoma (NB) is the most frequent extracranial pediatric tumor. Advanced forms of the disease (metastatic and/or refractory) have a dismal prognosis despite the combination of chemotherapy, radiotherapy, surgery and bone narrow transplants. These treatments carry severe side effects and, in some cases, compromise the life of the patient. MIBG has been widely applied in the medical diagnosis of NB due to its affinity for tumor cells through the norepinephrine transporter (NET), which is expressed in 90% of NB tumors. The exclusive accumulation of MIBG in neuroblastoma has been widely studied; however, its properties have been never exploited as a targeting agent in nanocarrier drug delivery systems. Several structural analogues of MIBG have been prepared and attached on the surface of nanocarriers. Their selective internalization has been tested against human neuroblastoma cells, which show, in the best case, cellular uptake four times higher than that of the naked nanosystem. Furthermore, in vivo experiments showed preferential and selective accumulation and retention of the targeted nanosystem comparing with the naked and only PEGylated counterpart systems. This novel nanosystem could be easily applicable to all kinds of drug delivery nanocarriers, providing a universal tool for neuroblastoma chemotherapies that is superior to classical approaches through a novel nanosystem exclusively designed to target this terrible malignancy.

[Endocrine-metabolic adjustments during Ramadan fasting in young athletes]. / Ajustes endocrino-metabólicos durante el ayuno de Ramadán en jóvenes deportistas.

The Islamic precept of R implies important physiological modifications due to the hydric and dietetic restrictions along a whole month plus a day, all of which have a crucial repercussion over the physical and intellectual performance of Muslims, particularly in occidental societies, in which there is no hour readjustments for daily activities. Among the imposed modifications by Ramadan in daily habits, intermittent fasting along day and night causes adaptation mechanisms to optimize the energy consumption. The objective of this study was to analyze the metabolic-endocrine changes that happen during daily working hours, along the month of fasting in young subjects who have to continue their usual activities and sport training. Ten young muslim subjects, male, healthy, set to sport training, ages in between 18 and 25 who completed Ramadan. Plasma biochemical and hormonal parameters were analyzed in plasma, a week before Ramadan, in the first and fourth of the fasting month and a week after conclusion. During Ramadan, have been observed a drop of biochemical parameters along daytime, especially those related to glycemia, being these changes stronger in the first week. The concentration of cortisol found to be significantly high during the whole month as a consequence of adaptation to the change of circadian secretion rhythms. Ramadan obliges subject's organisms to readjust their endocrine and metabolic system in order to preserve the energetic efficiency during daytime. This auto control becomes more efficient as long as the month advances due to physiological adaptations.

Ajustes endocrino-metabólicos durante el ayuno de Ramadán en jóvenes deportistas / Endocrine-metabolic adjustments during Ramadan fasting in young athletes

El precepto islámico del Ramadán (R), implica importantes modificaciones fisiológicas debido a las restricciones hídricas y dietéticas a lo largo del día y durante un mes, lo que tiene una especial repercusión física e intelectual de los musulmanes, particularmente en sociedades occidentales, en las que no se producen reajustes horarios para las actividades cotidianas. Entre las modificaciones impuestas por el R, el ayuno intermitente día/noche, desencadena mecanismos de adaptación para rentabilizar el consumo energético. El objetivo del presente estudio ha sido valorar algunos cambios endocrinometabólicos que acontecen a lo largo de la jornada, durante el mes de ayuno, en jóvenes que tienen que continuar con su actividad y entrenamiento deportivo habitual. Diez jóvenes musulmanes, varones, sanos, sometidos a entrenamiento deportivo, con edades entre 18 y 25 años que realizaron el R. Se analizaron parámetros bioquímicos y hormonales en plasma, una semana previa al R, primera y cuarta del periodo de ayuno (mañana y tarde) y semana posterior. Durante el R, se observa un descenso de los parámetros bioquímicos a lo largo del día, especialmente de la glucemia, siendo estos cambios más evidentes en la primera semana. La concentración de cortisol se encuentran significativamente elevada durante todo el mes, como consecuencia del cambio de ritmo circadiano de secreción. El R obliga al organismo a un ajuste endocrino-metabólico con el fin de preservar la eficiencia energética durante la jornada. Este control se vuelve más eficaz conforme avanza el mes de ayuno y la consecuente adaptación fisiológica.

The Islamic precept of R implies important physiological modifications due to the hydric and dietetic restrictions along a whole month plus a day, all of which have a crucial repercussion over the physical and intellectual performance of Muslims, particularly in occidental societies, in which there is no hour readjustments for daily activities. Among the imposed modifications by Ramadan in daily habits, intermittent fasting along day and night causes adaptation mechanisms to optimize the energy consumption. The objective of this study was to analyze the metabolic-endocrine changes that happen during daily working hours, along the month of fasting in young subjects who have to continue their usual activities and sport training. Ten young muslim subjects, male, healthy, set to sport training, ages in between 18 and 25 who completed Ramadan. Plasma biochemical and hormonal parameters were analyzed in plasma, a week before Ramadan, in the first and fourth of the fasting month and a week after conclusion. During Ramadan, have been observed a drop of biochemical parameters along daytime, especially those related to glycemia, being these changes stronger in the first week. The concentration of cortisol found to be significantly high during the whole month as a consequence of adaptation to the change of circadian secretion rhythms. Ramadan obliges subject´s organisms to readjust their endocrine and metabolic system in order to preserve the energetic efficiency during daytime. This auto control becomes more efficient as long as the month advances due to physiological adaptations.

Development of homogeneous and heterogenized rhodium(I) and palladium(II) complexes with ligands based on a chiral proton sponge building block and their application as catalysts.

Chiral compounds prepared from proton sponge building block 8-((2R,5R)-2,5-dimethylpyrrolidin-1-yl)naphthalen-1-amine were found to be effective chiral ligands for obtaining complexes of rhodium(I) and palladium(II) by reaction with [RhCl(cod)](2), PdCl(2)(cod) or Pd(OAc)(2). The complexes bearing triethoxysilane groups were immobilized on mesoporous MCM-41 in order to obtain new heterogeneous catalysts. Both materials are active in the hydrogenation of alkenes and could be recycled without loss of activity or enantioselectivity.

[The impact of therapy with TNF-blockers on health-related quality of life in rheumatoid arthritis patients. A pilot study]. / Calidad de vida relacionada con la salud tras terapia anti-factor de necrosis tumoral alfa en pacientes con artritis reumatoide. Un estudio piloto.

INTRODUCTION: The aim of this pilot study was to evaluate the initial response to 16 weeks of treatment with infliximab and etanercept of disease activity and quality of life in a cohort of 37 patients with established rheumatoid arthritis. PATIENTS AND METHOD: Patients were selected from the Unit of Rheumatology in Hospital Clínico San Cecilio from Granada, refractory to conventional treatment with disease modifying antirheumatic drugs. To assess the disease activity, Disease activity score (DAS28) was used and the measurement of quality of life was evaluated with the Spanish version of the SF-36 Health Survey (SF-36) and the RA-specific questionnaire QoL Scale (Quality of Life in Rheumatoid Arthritis). RESULTS: Preliminary results show a significant decrease in inflammatory activity of the disease and consequently in HRQL scores. The comparison with the general reference population shows a deviation well below average, especially in the "physical function" dimension with a rising response pattern in all dimensions. The correlation between specific scores (QoL-RA scale) and generic ones (SF-36) for HQ-treatment also showed significance, especially with the physical aggregate. DISCUSSION: An important limitation of the present study is the number of patients and the duration of the treatment; despite this, improvements in functional parameters and quality of life are evident and remain roughly stable since the first weeks of treatment. This allow us to continue the study and increase the number of patients. CONCLUSIONS: The preliminary results obtained with TNF-blockers after 16 weeks of treatment in RA objectively show the effectiveness of these drugs and also the perception by the patients of the effect on their quality of life.

Calidad de vida relacionada con la salud tras terapia anti-factor de necrosis tumoral alfa en pacientes con artritis reumatoide. Un estudio piloto / The impact of therapy with TNF-blockers on health-related quality of life in rheumatoid arthritis patients. A pilot study

Introducción. El objetivo de este estudio piloto ha sido valorar la respuesta inicial tras 16 semanas de tratamiento con infliximab y etanercept sobre la actividad de la enfermedad y la calidad de vida (CV), en una cohorte de 37 pacientes con artritis reumatoide establecida. Pacientes y método. Los pacientes fueron seleccionados en el Servicio de Reumatología del Hospital Clínico San Cecilio de Granada, por ser refractarios al tratamiento convencional con fármacos antirreumáticos modificadores de la enfermedad. Para evaluar la actividad de la enfermedad se utilizó el índice DAS28 (Disease Activity Score) y para CV, la versión española del Cuestionario de Salud SF-36 (Health Survey SF-36) y el cuestionario específico QoL-RA Scale (Quality of Life in Rheumatoid Arthritis). Resultados. Los resultados preliminares muestran una disminución significativa en la actividad inflamatoria y consecuentemente en las puntuaciones de la CV. La comparación con la población general de referencia muestra una desviación muy por debajo de la media, especialmente en la dimensión “función física” con un patrón de respuesta ascendente en todas las dimensiones. La correlación entre puntuaciones específicas (QoL-RA Scale) y genéricas (SF-36) de CV postratamiento, también mostraron significación, especialmente con el agregado físico. Discusión. Consideramos una limitación importante del estudio el número de pacientes y el tiempo de evolución postratamiento. No obstante, las mejorías en los diferentes parámetros funcionales y de CV son objetivables y permanecen prácticamente estables desde las primeras semanas de tratamiento, lo que nos permitirá continuar el estudio y ampliar el número de pacientes. Conclusiones. Los resultados preliminares obtenidos con anti-TNF alfa tras 16 semanas de tratamiento en artritis reumatoide, muestran la efectividad de los fármacos objetivamente y subjetivamente según la percepción del paciente sobre su CV (AU)

Introduction. The aim of this pilot study was to evaluate the initial response to 16 weeks of treatment with infliximab and etanercept of disease activity and quality of life in a cohort of 37 patients with established rheumatoid arthritis. Patients and method. Patients were selected from the Unit of Rheumatology in Hospital Clínico San Cecilio from Granada, refractory to conventional treatment with disease modifying antirheumatic drugs. To assess the disease activity, Disease activity score (DAS28) was used and the measurement of quality of life was evaluated with the Spanish version of the SF-36 Health Survey (SF-36) and the RA-specific questionnaire QoL Scale (Quality of Life in Rheumatoid Arthritis). Results. Preliminary results show a significant decrease in inflammatory activity of the disease and consequently in HRQL scores. The comparison with the general reference population shows a deviation well below average, especially in the “physical function” dimension with a rising response pattern in all dimensions. The correlation between specific scores (QoL-RA scale) and generic ones (SF-36) for HQ-treatment also showed significance, especially with the physical aggregate. Discussion. An important limitation of the present study is the number of patients and the duration of the treatment; despite this, improvements in functional parameters and quality of life are evident and remain roughly stable since the first weeks of treatment. This allow us to continue the study and increase the number of patients. Conclusions. The preliminary results obtained with TNF-blockers after 16 weeks of treatment in RA objectively show the effectiveness of these drugs and also the perception by the patients of the effect on their quality of life (AU)

Nivel funcional y calidad de vida en espondilitis anquilosante. Estudio piloto tras 16 semanas de tratamiento anti-TNF / Functional level and quality of life in ankylosing spondylitis, pilot study after 16 weeks TNF blocker treatment

Objetivo. El objetivo del presente estudio ha sido valorar el efecto de infliximab y etanercept, sobre la capacidad funcional y la calidad de vida relacionada con la salud (CVRS) de 13 pacientes, mayores de 65 años, con espondilitis anquilosante (EA). Pacientes y métodos. Se incluyeron de forma consecutiva aquellos pacientes mayores de 65 años, refractarios al tratamiento convencional con fármacos antireumáticos modificadores de la enfermedad (FAME) diagnosticados en el Servicio de Reumatología del Hospital Clínico San Cecilio de Granada. Para evaluar actividad de la enfermedad utilizamos el índice BASDAI (bath ankylosing spondylitis disease activity index); para capacidad funcional y CVRS, el índice BASFI (bath ankylosing spondylitis functional index) y ASQoL (ankylosing spondylitis quality of life) respectivamente. Resultados. Se trata de un estudio piloto para valorar la respuesta a fármacos anti-TNFalfa (bloqueantes del factor de necrosis tumoral alfa) de 13 pacientes con EA mayores de 65 años, en los que se constata la disminución de actividad de la enfermedad. Los valores medios de las puntuaciones del dolor y de la enfermedad (BASDAI), muestran un descenso de 6,72 a 3,67 y de 6,15 a 2,79 respectivamente (p<0,0001), por debajo de 4, considerado como respuesta aceptable. También hubo mejorías significativas en la capacidad funcional (BASFI) pasando de 6,15 a 2,79 (p<0,001) y de la calidad de vida (ASQoL) de 13,85 a 4,22 (p<0,0001). Conclusiones. Nuestros resultados están en la línea de lo informado por otros autores sobre la eficacia de los fármacos anti-TNF, reduciendo significativamente la sintomatología clínica inflamatoria de la enfermedad a las 16 semanas y mejorando la funcionalidad y CV en pacientes con EA, mayores de 65 años(AU)

Background and objectives. The aim of the present study is to assess the impact of infliximab and etanercept, TNF-alpha (tumour necrosis factor-alpha blockers) on functional disability and quality of life in thirteen patients over 65 years-old with ankylosing spondylitis (AS). Patients and methods. We consecutively included patients over 65 years-old, attending our clinic from Rheumatology Service in Hospital Clínico de Granada. These patients were all refractory to conventional therapy with disease-modifying anti-rheumatic drugs (DMARD). Disease activity was assessed using BASDAI index (bath ankylosing spondylitis disease activity index). Functional disability was assessed using BASFI (bath ankylosing spondylitis functional index) and ASQol index (ankylosing spondylitis quality of life index). Results. We present a pilot study with 13 patients over 65 years-old treated with TNF blockers for 16 weeks. A significant decrease in disease activity was observed. Mean values of VAS (visual analogue scale) pain scores and disease decreases significantly after treatment (from 6.72 to 3.67 and 6.15 to 2.79 respectively), less than 4, which is considered an acceptable BASDAI response. Functional ability (BASFI) and health related quality of life (HRQOL) improved significantly from 6.15 to 2.79 and 13.85 to 4.22. Conclusions. Our results are consistent with the data available in the literature about TNF blockers decreasing clinical signs of the disease. Disease activity had significantly decreased 16 weeks after the onset of TNF blocker therapy. Functionality and quality of life have been also improved in elderly people with AS(AU)

[Functional level and quality of life in ankylosing spondylitis, pilot study after 16 weeks TNF blocker treatment]. / Nivel funcional y calidad de vida en espondilitis anquilosante. Estudio piloto tras 16 semanas de tratamiento anti-TNF.

BACKGROUND AND OBJECTIVES: The aim of the present study is to assess the impact of infliximab and etanercept, TNF-alpha (tumour necrosis factor-alpha blockers) on functional disability and quality of life in thirteen patients over 65 years-old with ankylosing spondylitis (AS). PATIENTS AND METHODS: We consecutively included patients over 65 years-old, attending our clinic from Rheumatology Service in Hospital Clínico de Granada. These patients were all refractory to conventional therapy with disease-modifying anti-rheumatic drugs (DMARD). Disease activity was assessed using BASDAI index (bath ankylosing spondylitis disease activity index). Functional disability was assessed using BASFI (bath ankylosing spondylitis functional index) and ASQol index (ankylosing spondylitis quality of life index). RESULTS: We present a pilot study with 13 patients over 65 years-old treated with TNF blockers for 16 weeks. A significant decrease in disease activity was observed. Mean values of VAS (visual analogue scale) pain scores and disease decreases significantly after treatment (from 6.72 to 3.67 and 6.15 to 2.79 respectively), less than 4, which is considered an acceptable BASDAI response. Functional ability (BASFI) and health related quality of life (HRQOL) improved significantly from 6.15 to 2.79 and 13.85 to 4.22. CONCLUSIONS: Our results are consistent with the data available in the literature about TNF blockers decreasing clinical signs of the disease. Disease activity had significantly decreased 16 weeks after the onset of TNF blocker therapy. Functionality and quality of life have been also improved in elderly people with AS.

New chiral ligands bearing two N-heterocyclic carbene moieties at a dioxolane backbone. Gold, palladium and rhodium complexes as enantioselective catalysts.

Biscarbene ligands with two imidazolin-2-ylidene moieties at a chiral dioxolane backbone were used as ligands for gold, rhodium and palladium complexes. All new complexes showed varying degrees of enantioselectivity toward hydrogenation of prochiral alkenes with ees up to 95%.