157 research outputs found

    Lipid-polymer membranes as carriers for L-tryptophan : Molecular and metabolic properties

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    Polymerized liposomes encapsulating L-tryptophan were studied with the aim to characterize them as drug delivery systems for the treatment of several metabolic diseases that need an increased systemic L-tryptophan concentration, polymerized liposomes were obtained by UV irradiation of vesicles containing 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine (DC8,9PC) and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) in a 1:1 molar ratio, in the presence of 10 and 50 mol% of L-tryptophan (respect to total lipid concentration). Polymerization efficiency was studied spectrophotometrically. Also, bilayer packing at the polar head region was followed with the Merocyanine 540 (MC540) and specific interactions in the lipopolymers were studied by FTIR. High L-tryptophan concentrations (50 mol% respect to total lipid concentration) induced a higher amount of six- and nine-unit polymers. This phenomenon was induced because the L-tryptophan located outside the lipid membrane was included in it during the polymerization process and was thus responsible for the better accommodate of the polar head region. This was not possible with the lower amount of L-tryptophan (10 mol%). The stability of lipopolymers with different amounts of L-tryptophan was studied through release profiles. Polymerized liposomes with 50 mol% of L-tryptophan were able to retain around 80% of the amino acid after 24 hours, whereas those with 10 mol % of the amino acid were able to retain 20%. The metabolic activity of the Caco-2 cell line was also studied. Cytotoxic effects were low in the presence of polymerized liposomes, rendering a maximum percentage of cell death of 30%. In summary, this work stresses the relevance of nonspecific drug-polymerized membrane binding on L-tryptophan pharmacological interaction with possible pharmaceutical applications in liposomal drug delivery. Moreover, the absence of significant cytotoxic effects allows the system proposed to be applied in human health.Instituto Multidisciplinario de Biología Celula

    Lipid-polymer membranes as carriers for L-tryptophan : Molecular and metabolic properties

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    Polymerized liposomes encapsulating L-tryptophan were studied with the aim to characterize them as drug delivery systems for the treatment of several metabolic diseases that need an increased systemic L-tryptophan concentration, polymerized liposomes were obtained by UV irradiation of vesicles containing 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine (DC8,9PC) and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) in a 1:1 molar ratio, in the presence of 10 and 50 mol% of L-tryptophan (respect to total lipid concentration). Polymerization efficiency was studied spectrophotometrically. Also, bilayer packing at the polar head region was followed with the Merocyanine 540 (MC540) and specific interactions in the lipopolymers were studied by FTIR. High L-tryptophan concentrations (50 mol% respect to total lipid concentration) induced a higher amount of six- and nine-unit polymers. This phenomenon was induced because the L-tryptophan located outside the lipid membrane was included in it during the polymerization process and was thus responsible for the better accommodate of the polar head region. This was not possible with the lower amount of L-tryptophan (10 mol%). The stability of lipopolymers with different amounts of L-tryptophan was studied through release profiles. Polymerized liposomes with 50 mol% of L-tryptophan were able to retain around 80% of the amino acid after 24 hours, whereas those with 10 mol % of the amino acid were able to retain 20%. The metabolic activity of the Caco-2 cell line was also studied. Cytotoxic effects were low in the presence of polymerized liposomes, rendering a maximum percentage of cell death of 30%. In summary, this work stresses the relevance of nonspecific drug-polymerized membrane binding on L-tryptophan pharmacological interaction with possible pharmaceutical applications in liposomal drug delivery. Moreover, the absence of significant cytotoxic effects allows the system proposed to be applied in human health.Instituto Multidisciplinario de Biología Celula

    Traffic-based Control of Truck Platoons on Freeways

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    This abstract deals with the control of truck platoons traveling in freeways. In order to improve their travel performance, in terms of travelling times and comfort and to guarantee safety, a hierarchical control scheme is proposed for each platoon. At the high level, the reference speed is computed according to a PI-based control rule with the main aim of reducing the time spent by the platoon in the congested area. This reference speed is communicated to the low control level which implements a Linear Quadratic Tracking policy and determines the optimal speed for each truck in the platoon. The application of these hierarchical controllers to a case study shows the effectiveness of the proposed scheme

    All-cause and cause-specific mortality in rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis : a nationwide registry study

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    Objectives To explore mortality and causes of death among Norwegian patients with RA, PsA and axial spondyloarthritis (axSpA) compared with the general population by conducting a nationwide registry-based cohort study. Methods Patients with RA, PsA and axSpA were identified from the Norwegian Patient Registry based on ICD-10 codes between 2008 and 2017. Using age as the time variable, all-cause and cause-specific mortality were estimated between 2010 and 2017 with the Kaplan-Meier estimator and the cumulative incidence competing risk method, respectively. Sex-, education level-, health region- and age group-adjusted hazard ratios (HRs) for mortality were estimated using Cox regression models. Results We identified 36 095 RA, 18 700 PsA and 16 524 axSpA patients (70%, 53% and 45% women, respectively). RA and axSpA were associated with increased all-cause mortality (HR 1.45 [95% CI: 1.41, 1.48] and HR 1.38 [95% CI: 1.28, 1.38], respectively). Women but not men with PsA had a slightly increased mortality rate (HR 1.10 [95% CI: 1.00, 1.21] among women and 1.02 [95% CI: 0.93, 1.11] among men). For all patient groups as well as for the general population, the three leading causes of death were cardiovascular diseases, neoplasms and respiratory diseases. RA patients had increased mortality from all of these causes, while axSpA patients had increased mortality from cardiovascular and respiratory diseases. Conclusion Even in the era of modern treatments for IJDs, patients with RA and axSpA still have shortened life expectancy. Our findings warrant further attention to the prevention and management of comorbidities.Peer reviewe

    Effect of structure in ionised albumin based nanoparticle: Characterisation, Emodin interaction, and in vitro cytotoxicity

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    A γ–irradiated bovine albumin serum-based nanoparticle was characterised structurally, and functionally. The nanoparticle was characterised by A.F.M, D.L.S, zeta potential, T.E.M., gelelectrophoresis, and spectroscopy. We studied the stability of the nanoparticle at different pH values and against time, by fluorescence spectroscopy following the changes in the tryptophan environment in the nanoparticle. The nanoparticle was also functionalized with Folic Acid, its function as a nanovehicle was evaluated through its interaction with the hydrophobic drug Emodin. The binding and kinetic properties of the obtained complex were evaluated by biophysical methods as well as its toxicity in tumour cells. According to its biophysics, the nanoparticle is a spherical nanosized vehicle with a hydrodynamic diameter of 70 nm. Data obtained describe the nanoparticle as nontoxic for cancer cell lines. When combined with Emodin, the nanoparticle proved to be more active on MCF-7 cancer cell lines than the nanoparticle without Emodin. Significantly, the albumin aggregate preserves the main activity-function of albumin and improved characteristics as an excellent carrier of molecules. More than carrier properties, the nanoparticle alone induced an immune response in macrophages which may be advantageous in vaccine and cancer therapy formulation.Fil: Siri, Macarena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología - Universidad Nacional de Quilmes - GBEyB | Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología - Universidad Nacional de Quilmes - GBEyB | Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología - Universidad Nacional de Quilmes - GBEyB; ArgentinaFil: Fernandez Ruocco, Maria Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología - Universidad Nacional de Quilmes - GBEyB | Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología - Universidad Nacional de Quilmes - GBEyB | Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología - Universidad Nacional de Quilmes - GBEyB; Argentina. Universidade Federal do Rio de Janeiro; BrasilFil: Achilli, Estefanía Edith. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología - Universidad Nacional de Quilmes - GBEyB | Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología - Universidad Nacional de Quilmes - GBEyB | Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología - Universidad Nacional de Quilmes - GBEyB; ArgentinaFil: Pizzuto, Malvina. Université Libre de Bruxelles; BélgicaFil: Delgado, Juan Francisco. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ruysschaert, Jean Marie. Université Libre de Bruxelles; BélgicaFil: Grasselli, Mariano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología - Universidad Nacional de Quilmes - GBEyB | Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología - Universidad Nacional de Quilmes - GBEyB | Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología - Universidad Nacional de Quilmes - GBEyB; ArgentinaFil: Alonso, Silvia del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología - Universidad Nacional de Quilmes - GBEyB | Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología - Universidad Nacional de Quilmes - GBEyB | Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología - Universidad Nacional de Quilmes - GBEyB; Argentin

    HDAC Inhibition Improves the Sarcoendoplasmic Reticulum Ca2+-ATPase Activity in Cardiac Myocytes

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    SERCA2a is the Ca2+ ATPase playing the major contribution in cardiomyocyte (CM) calcium removal. Its activity can be regulated by both modulatory proteins and several post-translational modifications. The aim of the present work was to investigate whether the function of SERCA2 can be modulated by treating CMs with the histone deacetylase (HDAC) inhibitor suberanilohydroxamic acid (SAHA). The incubation with SAHA (2.5 \ub5M, 90 min) of CMs isolated from rat adult hearts resulted in an increase of SERCA2 acetylation level and improved ATPase activity. This was associated with a significant improvement of calcium transient recovery time and cell contractility. Previous reports have identified K464 as an acetylation site in human SERCA2. Mutants were generated where K464 was substituted with glutamine (Q) or arginine (R), mimicking constitutive acetylation or deacetylation, respectively. The K464Q mutation ameliorated ATPase activity and calcium transient recovery time, thus indicating that constitutive K464 acetylation has a positive impact on human SERCA2a (hSERCA2a) function. In conclusion, SAHA induced deacetylation inhibition had a positive impact on CM calcium handling, that, at least in part, was due to improved SERCA2 activity. This observation can provide the basis for the development of novel pharmacological approaches to ameliorate SERCA2 efficiency

    A role for Oncostatin M in the impairment of glucose homeostasis in obesity

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    CONTEXT: Oncostatin M (OSM) plays a key role in inflammation, but its regulation and function during obesity is not fully understood. OBJECTIVE: The aim of this study was to evaluate the relationship of OSM with the inflammatory state that leads to impaired glucose homeostasis in obesity. We also assessed whether OSM immunoneutralization could revert metabolic disturbances caused by a high-fat diet (HFD) in mice. DESIGN: 28 patients with severe obesity were included and stratified into two groups: (1) glucose levels 100 mg/dL. White adipose tissue was obtained to examine OSM gene expression. Human adipocytes were used to evaluate the effect of OSM in the inflammatory response, and HFD-fed C57BL/6J mice were injected with anti-OSM antibody to evaluate its effects. RESULTS: OSM expression was elevated in subcutaneous and visceral fat from patients with obesity and hyperglycemia, and correlated with Glut4 mRNA levels, serum insulin, homeostatic model assessment of insulin resistance, and inflammatory markers. OSM inhibited adipogenesis and induced inflammation in human adipocytes. Finally, OSM receptor knockout mice had increased Glut4 mRNA levels in adipose tissue, and OSM immunoneutralization resulted in a reduction of glucose levels and Ccl2 expression in adipose tissue from HFD-fed mice. CONCLUSIONS: OSM contributes to the inflammatory state during obesity and may be involved in the development of insulin resistance

    Differential association between S100A4 levels and insulin resistance in prepubertal children and adult subjects with clinically severe obesity

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    Objectives: S100A4 has been recently identified as an adipokine associated with insulin resistance (IR) in adult subjects with obesity. However, no data about its levels in children with obesity and only a few approaches regarding its potential mechanism of action have been reported. To obtain a deeper understanding of the role of S100A4 in obesity, (a) S100A4 levels were measured in prepubertal children and adult subjects with and without obesity and studied the relationship with IR and (b) the effects of S100A4 in cultured human adipocytes and vascular smooth muscle cells (VSMCs) were determined. Methods: Sixty-five children (50 with obesity, age 9.0 ±1.1 years and 15 normal weight, age 8.4 ±0.8 years) and fifty-nine adults (43 with severe obesity, age 46 ±11 years and 16 normal weight, age 45 ±9 years) were included. Blood from children and adults and adipose tissue samples from adults were obtained and analysed. Human adipocytes and VSMC were incubated with S100A4 to evaluate their response to this adipokine. Results: Circulating S100A4 levels were increased in both children (P = .002) and adults (P < .001) with obesity compared with their normal-weight controls. In subjects with obesity, S100A4 levels were associated with homeostatic model assessment-insulin resistance (HOMA-IR) in adults (βstd = .42, P = .008) but not in children (βstd = .12, P = .356). Human adipocytes were not sensitive to S100A4, while incubation with this adipokine significantly reduced inflammatory markers in VSMC. Conclusions: Our human data demonstrate that higher S100A4 levels are a marker of IR in adults with obesity but not in prepubertal children. Furthermore, the in vitro results suggest that S100A4 might exert an anti-inflammatory effect. Further studies will be necessary to determine whether S100A4 can be a therapeutic target for obesity
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