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Glucocorticoids are utilized for their anti-inflammatory properties in the skeletal muscle and arthritis. However, the major drawback of use of glucocorticoids is that it leads to senescence and toxicity. Therefore, based on the idea that decreasing particle size allows for increased surface area and bioavailability of the drug, in the present study, we hypothesized that nanodelivery of dexamethasone will offer increased efficacy and decreased toxicity. The dexamethasone-loaded poly(lactic-coglycolic acid) (PLGA) nanoparticles were prepared using nanoprecipitation method. The morphological characteristics of the nanoparticles were studied under scanning electron microscope. The particle size of nanoparticles was 217.5 [+ or -] 19.99 nm with polydispersity index of 0.14 [+ or -] 0.07. The nanoparticles encapsulation efficiency was 34.57% [+ or -] 1.99% with in vitro drug release profile exhibiting a sustained release pattern over 10 days. We identified improved skeletal muscle myoblast performance with improved closure of the wound along with increased cell viability at 10 nmol/L nano-dexamethasone-PLGA. However, dexamethasone solution (1 [micro]mol/L) was injurious to cells because the migration efficiency was decreased. In addition, the use of dexamethasone nanoparticles decreased lipopolysaccharide-induced lactate dehydrogenase release compared with dexamethasone solution. Taken together, the present study clearly demonstrates that delivery of PLGA-dexamethasone nanoparticles to the skeletal muscle cells is beneficial for treating inflammation and skeletal muscle function. Key words: dexamethasone, PLGA, nanoparticles, skeletal muscle. Les glucocorticoides sont utilises pour leurs proprietes anti-inflammatoires dans le muscle squelettique et l'arthrite. Cependant, le principal probleme de l'utilisation des glucocorticoides tient au fait qu'elle mene a de la senescence et de la toxicite. Par consequent, a partir de l'idee qu'en diminuant la taille des particules on augmente la surface de contact et la biodisponibilite du medicament, dans la presente etude, nous avons formule une hypothese selon laquelle l'administration de nanoparticules de dexamethasone permet d'en augmenter l'efficacite et d'en diminuer la toxicite. Nous avons prepare des nanoparticules d'acide poly(lactique co-glycolique) [ou PLGA pour << poly(lactic-co-glycolic acid)>>] chargee de dexamethasone a l'aide de la methode de nanoprecipitation. Nous avons etudie les caracteristiques morphologiques des nanoparticules a l'aide de la microscopie electronique par balayage. Les nanoparticules avaient une taille de 217,5 [+ or -] 19,99 nm avec un indice de polydispersion de 0,14 [+ or -] 0,07. L'efficacite de l'encapsulation des nanoparticules etait de 34,57 [+ or -] 1,99 % avec un profil in vitro de liberation du medicament presentant un schema de liberation soutenue sur 10 jours. Avec le complexe PLGA-nano-dexamethasone a 10 nmol/L, nous avons observe une amelioration de la performance des myoblastes du muscle squelettique avec une amelioration de la fermeture de plaie ainsi qu'une augmentation de la vitalite des cellules. Toutefois, une solution de dexamethasone (1 [micro]mol/L) provoquait des lesions cellulaires en raison d'une diminution de l'efficacite de la migration. De plus, l'utilisation de nanoparticules de dexamethasone entrainait une diminution de la liberation de lipopolysaccharides produite par la deshydrogenase lactique plus marquee qu'avec la solution de dexamethasone. Dans l'ensemble, la presente etude montre que l'administration de nanoparticules de PLGA-dexamethasone aux cellules de muscle squelettique est avantageuse pour traiter l'inflammation et le fonctionnement du muscle squelettique. [Traduit par la Redaction] Mots-cles: dexamethasone, PLGA, nanoparticules, muscle squelettique., Introduction Dexamethasone and other glucocorticoids are used for the treatment of inflammation and pain related to skeletal muscle injury, wound healing, and arthritis (Bijlsma 2012; Klein 2015; Vyvey 2010). However, [...]

Background Glucocorticosteroid (GC) is one of the most effective drugs available for the treatment of primary nephrotic syndrome (PNS) in children. However, some patients show little or no response to GC. The purpose of our research was to observe and describe the different levels of histone deacetylase-2 (HDAC2) expression in peripheral blood lymphocytes in children with PNS compared with various responses to the GC treatment, with the primary aim to assess the correlation between HDAC2 and GC resistance in PNS children. Methods Forty-eight patients with PNS suffering from their first attack prior to GC treatment were chosen as subjects. They were divided into two groups, those who had steroid-sensitive nephrotic syndrome (SSNS; n = 25) and those with steroid-resistant NS (SRNS; n = 23), according to their response to a 6-week course of oral prednisone. Twenty healthy children from the Physical Examination Center in the hospital served as the control group; Peripheral blood was collected at different time points prior to GC treatment and after regular therapy. RT-PCR, western blot, and enzyme-linked immunosorbent assay (ELISA) techniques were adopted to analyze HDAC2 mRNA, protein expression, and activity, respectively, in peripheral blood lymphocytes. The level of interleukin-8 (IL-8) in serum was measured by an ELISA. Results Prior to GC treatment, HDAC2 expression level and activity were lower in the SRNS group than in the SSNS and control group. A statistically significant difference in HDAC2 expression and activity were observed after GC treatment between these groups, with HDAC2 expression and activity lower in the SRNS group than in the SSNS and control groups. In the SSNS group, the expression and activity of HDAC2 were higher following GC treatment than prior to GC treatment. There was a clear difference in HDAC2 expression and activity of SRNS at the different time points. No statistically significant difference was found between the two groups. The pre-treatment and post-treatment serum IL-8 levels in the SRNS group were significantly higher than those in the SSNS group. HDAC2 from children with PNS before GC treatment and after regular therapy for 6 weeks was negatively correlated with serum IL-8 level. Conclusion The GC effect was influenced by the HDAC2 expression and activity, leading to decreased serum IL-8 levels in children with PNS. HDAC2 seems to be one of the markers of GC resistance in children with PNS., Author(s): Feng-Jun Guan [sup.1] , Qian-Qian Peng [sup.2] , Lin-li Wang [sup.1] , Xue-Bo Yan [sup.3] , Chen Dong [sup.1] , Xiao-Hua Jiang [sup.1] Author Affiliations: (1) Department of Pediatrics, [...]

Turmeric (Curcuma longa), a member of the ginger (Zingiberaceae) family, is used as a primary food staple in many countries. However, in addition to its use as a food staple, [...]

Glucocorticoid steroids such as prednisone are prescribed for chronic muscle conditions such as Duchenne muscular dystrophy, where their use is associated with prolonged ambulation. The positive effects of chronic steroid treatment in muscular dystrophy are paradoxical because these steroids are also known to trigger muscle atrophy. Chronic steroid use usually involves once-daily dosing, although weekly dosing in children has been suggested for its reduced side effects on behavior. In this work, we tested steroid dosing in mice and found that a single pulse of glucocorticoid steroids improved sarcolemmal repair through increased expression of annexins A1 and A6, which mediate myofiber repair. This increased expression was dependent on glucocorticoid response elements upstream of annexins and was reinforced by the expression of forkhead box O1 (FOXO1). We compared weekly versus daily steroid treatment in mouse models of acute muscle injury and in muscular dystrophy and determined that both regimens provided comparable benefits in terms of annexin gene expression and muscle repair. However, daily dosing activated atrophic pathways, including F-box protein 32 (Fbxo32), which encodes atrogin-1. Conversely, weekly steroid treatment in mdx mice improved muscle function and histopathology and concomitantly induced the ergogenic transcription factor Kruppel-like factor 15 (Klfl5) while decreasing Fbxo32. These findings suggest that intermittent, rather than daily, glucocorticoid steroid regimen promotes sarcolemmal repair and muscle recovery from injury while limiting atrophic remodeling., Introduction Glucocorticoid (GC) steroids are used to treat many chronic conditions ranging from lung disease to autoimmune disorders and muscle disease. It is estimated that more than 1% of the [...]