ABSTRACT
BACKGROUND: Antiphospholipid syndrome (APS) is the main cause of acquired thrombophilia where peripheral circulating cells such as monocytes have a key role. Currently, several studies have linked long non-coding RNAs (lncRNAs) in different inflammatory and autoimmune processes, including lupus. However, the role of lncRNAs in antiphospholipid syndrome is unknown, therefore, we aimed to select and measure expression levels of three lncRNAs based on its abundance in monocytes from APS patients. METHODS: Selection of lncRNAs candidates were carried out based on its abundance in monocytes and their relationship with Perez-Sanchez miRNA signature by using miRNet 2.0 bioinformatic tool, then lncRNAs expression levels was measured in monocytes by RT-qPCR. RESULTS: This is the first study to report that lncRNAs: FGD5-AS1, OIP5-AS1 and GAS5 are promising candidates for play a role on APS monocytes and they are expressed differently between patients and controls. CONCLUSIONS: OIP5-AS1, FGD5-AS1 and GAS5 are downregulated on monocytes from APS patients.
Subject(s)
Antiphospholipid Syndrome , MicroRNAs , RNA, Long Noncoding , Humans , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Antiphospholipid Syndrome/genetics , Monocytes/metabolism , MicroRNAs/genetics , Computational BiologyABSTRACT
SUMMARY Franz cells are one of the main tools to evaluate the transepithelial permeation of compounds through the performance of in vitro tests, these allows inferring the safety behavior of a compound in the skin. The objective of this research was to determine the permeation behavior of benzoic acid from complexes with polyelectrolytes (EuB 75 Cl 25 EuB 100), compared to benzoic acid without complexing, to infer its safety behavior. In a first phase, skin storage conditions were established comparatively evaluating the diffusion parameters (flow and permeation constant) and transepithelial water loss, using ears skin of freshly slaughtered pigs, stored in 1M NaCl at -2 °C for 3 days; it was worked under infinite doses conditions. Subsequently, the permeation test of two complexes between Eudragit E and benzoic acid, in comparison with benzoic acid, was carried out under finite dose conditions. The benzoic acid quantification was performed with an analytical method validated by HPLC-DAD. The results showed no significant differences showing that biological samples can be stored for 72 h under the conditions described. The permeation behavior of the complexed benzoic acid with respect to the free benzoic acid showed a better safety profile, since there was a lower permeation for the first case. These results show that complexation of benzoic acid could decrease the sensitivity reactions that it normally presents, based on the decrease in its permeation.
RESUMEN Las celdas de Franz son una de las herramientas para evaluar la permeación transe-pitelial de compuestos mediante la realización de ensayos in vitro, estos permiten inferir el comportamiento de seguridad de un compuesto en la piel. El objetivo de esta investigación fue determinar el comportamiento de permeación del ácido benzoico a partir de complejos con polielectrolitos (EuB 75 Cl 25 EuB 100) en comparación con el ácido benzoico sin complejar, para inferir su comportamiento de seguridad. En una primera fase, se establecieron las condiciones de almacenamiento de la piel comparando los parámetros de difusión (flujo y constante de permeación) y pérdida de agua transepitelial, empleando piel de orejas de cerdos recién sacrificados, almacenadas en NaCl 1M a -2°C por 3 días; se trabajó bajo condiciones de dosis infinitas. Posteriormente, se realizó el ensayo de permeación de dos complejos entre ácido benzoico y Eudragit E, en comparación con el ácido benzoico, bajo condiciones de dosis finitas. La cuantificación del ácido benzoico fue realizada con un método analítico validado por HPLC-DAD. Los resultados evidenciaron que las muestras biológicas pueden almacenarse durante 72 h en las condiciones descritas. El comportamiento de permeación del ácido benzoico complejado respecto al ácido benzoico libre demostró tener un mejor perfil de seguridad, puesto que hubo una menor permeación para el primer caso. Estos resultados demuestran que la complejación del ácido benzoico podría disminuir las reacciones de sensibilidad que normalmente este presenta, basándose en la disminución de su permeación.
ABSTRACT
RESUMEN En el presente estudio se realizó la validación de una metodología analítica por cromatografía líquida de alta eficiencia con detector de arreglo de diodos (HPLC-DAD) para la cuantificación del ácido benzoico en complejos polielectrolíticos, obtenidos con Eudragit® E100. Para ello se evaluaron las características de desempeño determinando que la metodología es selectiva; lineal en el rango de concentraciones de 2 a 10 fíg/mL; precisa con un RSD inferior a un 2%; exacta con un porcentaje de recuperación de un 98,7% y se establecieron límites de cuantificación (LOQ) de 0,72 y de 1,56 (g/mL para el sistema y método respectivamente. De acuerdo a estos resultados, la metodología analítica es adecuada para evaluar la permeación in vitro, del ácido benzoico incluido en los complejos polielectrolíticos a través de piel porcina, empleando celdas de Franz.
SUMMARY This paper presents the studies carried out about the validation of an analytical methodology by high performance liquid chromatography with diode array detector (HPLC-DAD) for the quantification of benzoic acid in polyelectrolyte complexes obtained with Eudragit® E100. Performance characteristics of the methodology were evaluated, finding that this is selective; linear in the concentration range of 2 to 10 (g / mL; accurate with a RSD of less than 2%, exact with a recovery percentage of 98.7% and quantification limits of 0.72 and 1.56 fig / mL were established for the system and method respectively. According with this results, the analytical methodology is adequate to evaluate the in vitro permeation of benzoic acid, in polyelectrolyte complexes, through porcine skin in Franz cells.
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Objective: To characterize the multifractal behavior of the beat to beat heart-period or RR fluctuations in fibromyalgia patients (FM) in comparison with healthy-matched subjects. Methods: Multifractral detrended fluctuation analysis (MDFA) was used to study multifractality in heartbeat times-series from 30 female healthy subjects and 30 female patients with fibromyalgia during day and night periods.The multifractal changes as derived from the magnitude and sign analysis of these RR fluctuations were also assessed. Results: The RR fluctuations dynamics of healthy subjects showed a broad multifractal spectrum. By contrast, a noticeable decrease in multifractality and non-linearity was observed for patients with fibromyalgia. In addition, the spectra corresponding to FM subjects were located on the average to the right of the spectra of healthy individuals, indicating that the local scaling exponents reflect a smoother behavior compared to healthy dynamics. Moreover, the multifractal analysis as applied to the magnitude and sign heartbeat series confirmed that, in addition to a decreased nonlinearity, fibromyalgia patients presented stronger anticorrelation in directionality, which did not remain invariant for small or rather larger fluctuations as it occurred in healthy subjects. Conclusion: When compared to healthy controls, fibromyalgia patients display decreased nonlinearity and stronger anticorrelations in heart period fluctuations. These findings reinforce the hypothesis of the potential role of the dysfunctional autonomic nervous system in the pathogenesis of fibromyalgia.
ABSTRACT
BACKGROUND: The pharmacologic management of rheumatoid arthritis has progressed substantially over the past years. It is therefore desirable that existing information be periodically updated. There are several published international guidelines for the treatment of rheumatoid arthritis that hardly adapt to the Mexican health system because of its limited healthcare resources. Hence, it is imperative to unify the existing recommendations and to incorporate them to a set of clinical, updated recommendations; the Mexican College of Rheumatology developed these recommendations in order to offer an integral management approach of rheumatoid arthritis according to the resources of the Mexican health system. OBJECTIVE: To review, update and improve the available evidence within clinical practice guidelines on the pharmacological management of rheumatoid arthritis and produce a set of recommendations adapted to the Mexican health system, according to evidence available through December 2012. METHODS: The working group was composed of 30 trained and experienced rheumatologists with a high quality of clinical knowledge and judgment. Recommendations were based on the highest quality evidence from the previously established treatment guidelines, meta-analysis and controlled clinical trials for the adult population with rheumatoid arthritis. RESULTS: During the conformation of this document, each working group settled the existing evidence from the different topics according to their experience. Finally, all the evidence and decisions were unified into a single document, treatment algorithm and drug standardization tables. CONCLUSIONS: This update of the Mexican Guidelines for the Pharmacologic Treatment of Rheumatoid Arthritis provides the highest quality information available at the time the working group undertook this review and contextualizes its use for the complex Mexican health system.