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1.
Foot Ankle Surg ; 2024 Mar 21.
Article in English | MEDLINE | ID: mdl-38575484

ABSTRACT

BACKGROUND: The decision to perform amputation of a limb in a patient with diabetic foot ulcer (DFU) is not an easy task. Prediction models aim to help the surgeon in decision making scenarios. Currently there are no prediction model to determine lower limb amputation during the first 30 days of hospitalization for patients with DFU. METHODS: Classification And Regression Tree analysis was applied on data from a retrospective cohort of patients hospitalized for the management of diabetic foot ulcer, using an existing database from two Orthopaedics and Traumatology departments. The secondary analysis identified independent variables that can predict lower limb amputation (mayor or minor) during the first 30 days of hospitalization. RESULTS: Of the 573 patients in the database, 290 feet underwent a lower limb amputation during the first 30 days of hospitalization. Six different models were developed using a loss matrix to evaluate the error of not detecting false negatives. The selected tree produced 13 terminal nodes and after the pruning process, only one division remained in the optimal tree (Sensitivity: 69%, Specificity: 75%, Area Under the Curve: 0.76, Complexity Parameter: 0.01, Error: 0.85). Among the studied variables, the Wagner classification with a cut-off grade of 3 exceeded others in its predicting capacity. CONCLUSIONS: Wagner classification was the variable with the best capacity for predicting amputation within 30 days. Infectious state and vascular occlusion described indirectly by this classification reflects the importance of taking quick decisions in those patients with a higher compromise of these two conditions. Finally, an external validation of the model is still required. LEVEL OF EVIDENCE: III.

2.
J Synchrotron Radiat ; 31(Pt 2): 336-342, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38372673

ABSTRACT

This work presents a detailed analysis of the performance of X-ray magnetic circular dichroism photoemission electron microscopy (XMCD-PEEM) as a tool for vector reconstruction of magnetization. For this, 360° domain wall ring structures which form in a synthetic antiferromagnet are chosen as the model to conduct the quantitative analysis. An assessment is made of how the quality of the results is affected depending on the number of projections that are involved in the reconstruction process, as well as their angular distribution. For this a self-consistent error metric is developed which allows an estimation of the optimum azimuthal rotation angular range and number of projections. This work thus proposes XMCD-PEEM as a powerful tool for vector imaging of complex 3D magnetic structures.

3.
J Dairy Sci ; 102(11): 9749-9762, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31495617

ABSTRACT

One of the main challenges in the food industry is to design strategies for the successful incorporation of natural sources of bioactive compounds. Recently, yogurts and other fermented dairy beverages have been proposed as ideal carriers of such bioactive compounds such as fatty acids and antioxidants that could improve consumers' health. However, the incorporation of new ingredients causes functional and structural modifications that may affect the consumers' preferences. In this work, a dairy beverage model supplemented with oleic acid has been designed by partial substitution of milk by Candida utilis single-cell protein extract. The changes in the structural properties of this new beverage were evaluated by following the fermentation process, pH, aggregate size, microstructure, and changes in rheological properties. Furthermore, molecular dynamics simulations were carried out to analyze the interaction between its main components. Our data revealed that samples with a percentage of milk substitution of 30% showed a higher viscosity as compared with the other percentages and less viscosity than the control (no substitution). These samples were then selected for fortification by incorporating oleic acid microcapsules. A concentration of 1.5 g/100 g was shown to be the optimal quantity of microcapsules for oleic acid supplementation. Molecular dynamic simulations revealed glutathione as an important component of the micro-gel structure. The present study forms the basis for novel studies where Candida utilis single-cell protein and microencapsulated essential oils could be used to design innovative bioproducts.


Subject(s)
Beverages/analysis , Candida/chemistry , Dietary Proteins/chemistry , Oleic Acid/chemistry , Animals , Antioxidants/analysis , Dietary Supplements , Fatty Acids/analysis , Fermentation , Glutathione/metabolism , Hydrogen-Ion Concentration , Milk/chemistry , Oils, Volatile/chemistry , Rheology , Viscosity
4.
Rev Esp Anestesiol Reanim (Engl Ed) ; 66(2): 72-77, 2019 Feb.
Article in English, Spanish | MEDLINE | ID: mdl-30424890

ABSTRACT

BACKGROUND AND OBJECTIVES: Practice guidelines for preoperative fasting have not clearly established the fasting time needed after oral administration of water-soluble contrast media. The aim of this study was to determine the time required for the gastric emptying during the water-soluble contrast media in patients with acute abdominal pain. METHODS: This prospective longitudinal study included sixty-eight patients older than 18 years of age with acute abdominal pain, who required a water-soluble contrast media enhanced abdominal computed tomography study. Plain radiographs were obtained hourly until complete the gastric emptying. Patients with probable bowel obstruction were not included in the study. RESULTS: A total of 31 (45,6%), 54 (79,4%), and 64 (94,1%) patients achieved a complete gastric clearance of barium in 1, 2 and 3 hours, respectively. All patients achieved complete emptying of water-soluble contrast media within 6 hours. Gastric emptying time was not associated with gender (P=0,44), body mass index (P=.35), fasting time prior to water-soluble contrast media intake (P=0,12), administration of opioids in the emergency room (P=0,7), and the presence of comorbidities (P=0,36). CONCLUSION: Ninety-four percent of the patients with acute abdominal pain achieved complete gastric emptying within 3hours after the administration of water-soluble contrast media. All of them achieved complete gastric emptying within 6hours. The results suggested 6hours after oral intake of the contrast media is enough to complete transit of water-soluble contrast media through the stomach and avoid unnecessary risks.


Subject(s)
Abdomen, Acute/diagnostic imaging , Barium Sulfate/pharmacokinetics , Contrast Media/pharmacokinetics , Fasting , Gastric Emptying , Tomography, X-Ray Computed/methods , Abdomen, Acute/physiopathology , Adult , Barium Sulfate/administration & dosage , Diatrizoate/administration & dosage , Diatrizoate Meglumine/administration & dosage , Female , Humans , Longitudinal Studies , Male , Practice Guidelines as Topic , Prospective Studies , Sex Factors , Solubility , Time Factors
5.
J. nurs. health ; 8(2): e188310, Set. 2018.
Article in Spanish | BDENF - Nursing | ID: biblio-1029192

ABSTRACT

Objetivo: describir la experiencia de la implementación de estrategias participativas basadas en lahistoria de vida y el audiovisual, como herramientas terapéuticas aplicadas a una persona adulta condiagnóstico de esquizofrenia. Métodos: estudio de Investigación – Acción – Participación,desarrollado en el contexto de la Rehabilitación Basada en Comunidad aplicada en Bogotá - Colombia.Resultados: las acciones participativas y dialogantes, lúdicas, creativas, fortalecen la funcionalidadde la comunidad terapéutica, así como su impacto sobre la rehabilitación individual. El desarrollode la estrategia audiovisual y de socialización permiten reconstruir significados e identidades deutilidad terapéutica, las cuales propician recursos personales que generan nuevos pensamientos yemociones. Conclusiones: es pertinente dar lugar a las posibilidades terapéuticas de laRehabilitación, mediante los aportes de distintos actores sociales, dinamizan y transforman laexperiencia de enfermedad a nivel individual, medio-ambiental, relacional, y comunitario;destacando en ello el poder significador asociado para el sujeto y su entorno social.


Objetivo: descrever a experiência da implementação de estratégias participativas baseadas nahistória de vida e no audiovisual, como ferramentas terapêuticas aplicadas a uma pessoa adultadiagnosticada com esquizofrenia. Métodos: estudo de Pesquisa - Ação - Participação, desenvolvido nocontexto da Reabilitação Baseada na Comunidade aplicada em um Centro de Reabilitação da cidadede Bogotá, Colômbia. Resultados: ações participativas e dialógicas, lúdicas e criativas fortalecem afuncionalidade da comunidade terapêutica, bem como seu impacto na reabilitação individual. Odesenvolvimento da estratégia: audiovisual e socialização baseada na participação permitereconstruir significados e identidades de utilidade terapêutica, que propiciam recursos pessoais que geram novos pensamentos e emoções. Conclusões: há possibilidades terapêuticas desse tipo dereabilitação, através das contribuições de diferentes atores sociais, que dinamizam e transformam aexperiência da doença no nível individual, ambiental, relacional e comunitário; enfatizando nele opoder significante associado ao próprio sujeito e ao seu ambiente social.


Objective: to describe the experience of the implementation of participatory strategies based onthe history of life and audiovisual, as therapeutic tools applied to an adult person diagnosed withschizophrenia. Methods: Research - Action - Participation study, developed in the context ofCommunity Based Rehabilitation applied in Bogotá, Colombia. Results: participative and dialogic,playful and creative actions strengthen the functionality of the therapeutic community, as well asits impact on individual rehabilitation. The development of the strategy: audiovisual andsocialization based on participation allows reconstructing meanings and identities of therapeuticutility, which propitiate personal resources that generate new thoughts and emotions. Conclusions:there are therapeutic possibilities of these rehabilitation, through the contributions of differentsocial actors, which energize and transform the disease experience at the individual, environmental,relational and community level; emphasizing in it the associated signifying power for the subjecthimself and for his social environment.


Subject(s)
Humans , Rehabilitation Nursing , Schizophrenia , Community Participation
6.
J Transl Med ; 14(1): 289, 2016 10 13.
Article in English | MEDLINE | ID: mdl-27733175

ABSTRACT

BACKGROUND: Certain glomerulopathies are associated with increased levels of CD80 (B7-1). We measured the urinary excretion of CD80, podocyturia and proteinuria in controls and in subjects with Fabry disease either untreated or on enzyme replacement therapy (ERT). METHODS: Cross-sectional study including 65 individuals: controls (n = 20) and Fabry patients (n = 45, 23 of them not on ERT and 22 on ERT). Variables included age, gender, urinary protein/creatinine ratio (UPCR), estimated glomerular filtration rate (eGFR), urinary uCD80/creatinine ratio (uCD80) and podocyturia. CD80 mRNA expression in response to lyso-Gb3, a bioactive glycolipid accumulated in Fabry disease, was studied in cultured human podocytes. RESULTS: Controls and Fabry patients did not differ in age, eGFR and gender. However, UPCR, uCD80 and podocyturia were significantly higher in Fabry patients than in controls. As expected, Fabry patients not on ERT were younger and a higher percentage were females. Non-ERT Fabry patients had less advanced kidney disease than ERT Fabry patients: UPCR was lower and eGFR higher, but uCD80 and podocyturia did not differ between non-ERT or ERT Fabry patients. There was a significant correlation between uCD80 and UPCR in the whole population (r 0.44, p 0.0005) and in Fabry patients (r 0.42, p 0.0046). Lyso-Gb3 at concentrations found in the circulation of Fabry patients increased uCD80 expression in cultured podocytes. CONCLUSIONS: Fabry disease is characterized by early occurrence of increased uCD80 excretion that appears to be a consequence of glycolipid accumulation. The potential for uCD80 excretion to reflect early, subclinical renal Fabry involvement should be further studied.


Subject(s)
B7-1 Antigen/urine , Fabry Disease/pathology , Fabry Disease/urine , Podocytes/metabolism , Podocytes/pathology , Adolescent , Adult , Aged , B7-1 Antigen/genetics , B7-1 Antigen/metabolism , Case-Control Studies , Cells, Cultured , Child , Fabry Disease/metabolism , Female , Glycolipids/metabolism , Humans , Male , Middle Aged , RNA, Messenger/genetics , RNA, Messenger/metabolism , Sphingolipids/metabolism , Young Adult
7.
Cell Death Dis ; 7: e2305, 2016 07 21.
Article in English | MEDLINE | ID: mdl-27441657

ABSTRACT

Vascular calcification (VC) is associated with increased cardiovascular mortality in aging, chronic kidney disease (CKD), type 2 diabetes mellitus (T2DM) and atherosclerosis. TNF-like weak inducer of apoptosis (TWEAK) recently emerged as a new biomarker for the diagnosis and prognosis of cardiovascular diseases. TWEAK binding to its functional receptor Fn14 was reported to promote several steps of atherosclerotic plaque progression. However, no information is currently available on the role of TWEAK/Fn14 on the development of medial calcification, which is highly prevalent in aging, CKD and T2DM. This study explored the involvement of TWEAK in human vascular smooth muscle cells (h-VSMCs) calcification in vitro. We report that TWEAK binding to Fn14 promotes inorganic phosphate-induced h-VSMCs calcification, favors h-VSMCs osteogenic transition, decreasing acta2 and myh11 and increasing bmp2 mRNA and tissue non-specific alkaline phosphatase (TNAP), and increases MMP9 activity. Blockade of the canonical NFκB pathway reduced by 80% TWEAK pro-calcific properties and decreased osteogenic transition, TNAP and MMP9 activity. Blockade of non-canonical NFκB signaling by a siRNA targeting RelB reduced by 20% TWEAK pro-calcific effects and decreased TWEAK-induced loss of h-VSMCs contractile phenotype and MMP9 activity, without modulating bmp2 mRNA or TNAP activity. Inhibition of ERK1/2 activation by a MAPK kinase inhibitor did not influence TWEAK pro-calcific properties. Our results suggest that TWEAK/Fn14 directly favors inorganic phosphate-induced h-VSMCs calcification by activation of both canonical and non-canonical NFκB pathways. Given the availability of neutralizing anti-TWEAK strategies, our study sheds light on the TWEAK/Fn14 axis as a novel therapeutic target in the prevention of VC.


Subject(s)
Muscle, Smooth, Vascular/metabolism , Myocytes, Smooth Muscle/metabolism , Phosphates/pharmacology , Receptors, Tumor Necrosis Factor/genetics , Transcription Factor RelB/genetics , Tumor Necrosis Factors/genetics , Actins/genetics , Actins/metabolism , Alkaline Phosphatase/genetics , Alkaline Phosphatase/metabolism , Bone Morphogenetic Protein 2/genetics , Bone Morphogenetic Protein 2/metabolism , Cytokine TWEAK , Gene Expression Regulation , Humans , Matrix Metalloproteinase 9/genetics , Matrix Metalloproteinase 9/metabolism , Mitogen-Activated Protein Kinase 1/genetics , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/genetics , Mitogen-Activated Protein Kinase 3/metabolism , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/pathology , Myocytes, Smooth Muscle/drug effects , Myocytes, Smooth Muscle/pathology , Myosin Heavy Chains/genetics , Myosin Heavy Chains/metabolism , Phosphates/metabolism , Primary Cell Culture , Protein Binding , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism , Receptors, Tumor Necrosis Factor/metabolism , Signal Transduction , TWEAK Receptor , Transcription Factor RelB/antagonists & inhibitors , Transcription Factor RelB/metabolism , Tumor Necrosis Factors/metabolism , Vascular Calcification/genetics , Vascular Calcification/metabolism , Vascular Calcification/pathology
8.
ScientificWorldJournal ; 2015: 394956, 2015.
Article in English | MEDLINE | ID: mdl-26247057

ABSTRACT

A novel cross-layer optimized video adaptation driven by perceptual semantics is presented. The design target is streamed live video to enhance situational awareness in challenging communications conditions. Conventional solutions for recreational applications are inadequate and novel quality of experience (QoE) framework is proposed which allows fully controlled adaptation and enables perceptual semantic feedback. The framework relies on temporal/spatial abstraction for video applications serving beyond recreational purposes. An underlying cross-layer optimization technique takes into account feedback on network congestion (time) and erasures (space) to best distribute available (scarce) bandwidth. Systematic random linear network coding (SRNC) adds reliability while preserving perceptual semantics. Objective metrics of the perceptual features in QoE show homogeneous high performance when using the proposed scheme. Finally, the proposed scheme is in line with content-aware trends, by complying with information-centric-networking philosophy and architecture.

9.
Cell Death Dis ; 6: e1644, 2015 Feb 12.
Article in English | MEDLINE | ID: mdl-25675304

ABSTRACT

Albuminuria promotes tubular injury and cell death, and is associated with faster progression of chronic kidney disease (CKD) to end-stage renal disease. However, the molecular mechanisms regulating tubular cell death in response to albuminuria are not fully understood. Brain abundant signal protein 1 (BASP1) was recently shown to mediate glucose-induced apoptosis in tubular cells. We have studied the role of BASP1 in albumin-induced tubular cell death. BASP1 expression was studied in experimental puromycin aminonucleoside-induced nephrotic syndrome in rats and in human nephrotic syndrome. The role of BASP1 in albumin-induced apoptosis was studied in cultured human HK2 proximal tubular epithelial cells. Puromycin aminonucleoside induced proteinuria and increased total kidney BASP1 mRNA and protein expression. Immunohistochemistry localized the increased BASP1 to tubular cells. BASP1 expression colocalized with deoxynucleotidyl-transferase-mediated dUTP nick-end labeling staining for apoptotic cells. Increased tubular BASP1 expression was observed in human proteinuric nephropathy by immunohistochemistry, providing evidence for potential clinical relevance. In cultured tubular cells, albumin induced apoptosis and increased BASP1 mRNA and protein expression at 6-48 h. Confocal microscopy localized the increased BASP1 expression in albumin-treated cells mainly to the perinuclear area. A peripheral location near the cell membrane was more conspicuous in albumin-treated apoptotic cells, where it colocalized with actin. Inhibition of BASP1 expression by a BASP1 siRNA protected from albumin-induced apoptosis. In conclusion, albumin-induced apoptosis in tubular cells is BASP1-dependent. This information may be used to design novel therapeutic approaches to slow CKD progression based on protection of tubular cells from the adverse consequences of albuminuria.


Subject(s)
Albumins/pharmacology , Calmodulin-Binding Proteins/metabolism , Cytoskeletal Proteins/metabolism , Membrane Proteins/metabolism , Nerve Tissue Proteins/metabolism , Repressor Proteins/metabolism , Animals , Apoptosis/drug effects , Apoptosis/genetics , Blotting, Western , Calmodulin-Binding Proteins/genetics , Cell Line , Cytoskeletal Proteins/genetics , Female , Humans , Immunohistochemistry , Kidney Tubules, Proximal/cytology , Kidney Tubules, Proximal/metabolism , Male , Membrane Proteins/genetics , Microscopy, Confocal , Nerve Tissue Proteins/genetics , RNA, Small Interfering/genetics , Rats , Repressor Proteins/genetics
10.
Rev Sci Instrum ; 85(5): 053904, 2014 May.
Article in English | MEDLINE | ID: mdl-24880384

ABSTRACT

A vectorial magneto-optic Kerr effect (v-MOKE) setup with simultaneous and quantitative determination of the two in-plane magnetization components is described. The setup provides both polarization rotations and reflectivity changes at the same time for a given sample orientation with respect to a variable external magnetic field, as well as allowing full angular studies. A classical description based on the Jones formalism is used to calculate the setup's properties. The use of different incoming light polarizations and/or MOKE geometries, as well as the errors due to misalignment and solutions are discussed. To illustrate the capabilities of the setup a detailed study of a model four-fold anisotropy system is presented. Among others, the setup allows to study the angular dependence of the hysteresis phenomena, remanences, critical fields, and magnetization reversal processes, as well as the accurate determination of the easy and hard magnetization directions, domain wall orientations, and magnetic anisotropies.

11.
Nat Commun ; 5: 3853, 2014 May 16.
Article in English | MEDLINE | ID: mdl-24834863

ABSTRACT

There are numerous indications that adsorbed particles on a surface do not desorb statistically, but that their spatial distribution is important. Evidence almost exclusively comes from temperature-programmed desorption, the standard method for measuring desorption rates. However, this method, as a kinetics experiment, cannot uniquely prove an atomic mechanism. Here we report a low-energy electron microscopy investigation in which a surface is microscopically imaged while simultaneously temperature-programmed desorption is recorded. The data show that during desorption of oxygen molecules from a silver single crystal surface, islands of oxygen atoms are present. By correlating the microscopy and the kinetics data, a model is derived that includes the shapes of the islands and assumes that the oxygen molecules desorb from the island edges. The model quantitatively reproduces the complex desorption kinetics, confirming that desorption is affected by islands and that the often used mean-field treatment is inappropriate.

12.
Ultramicroscopy ; 130: 82-6, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23611842

ABSTRACT

The structural and magnetic properties of Fe-Pd nanostructures grown on regular alternating Pd and oxygen stripes on the W(110) surface are studied using SPELEEM methods. The self-organized Pd-O stripe template, formed at about 1000 °C and aligned with the [001] direction, has an average period of only few tens nm and is preserved upon quenching the sample temperature to ambient conditions. Fe is shown to preferentially bond to the Pd stripes, forming an Fe-Pd surface alloy within the stripe phase. The magnetic easy axis is found to be aligned perpendicular to the Fe-Pd stripe axis.

13.
J Phys Condens Matter ; 25(17): 176004, 2013 May 01.
Article in English | MEDLINE | ID: mdl-23567900

ABSTRACT

We study the effect of magnetocrystalline anisotropy on the magnetic configurations of La0.7Sr0.3MnO3 bar and triangle elements using photoemission electron microscopy imaging. The dominant remanent state is a low energy flux-closure state for both thin (15 nm) and thick (50 nm) elements. The magnetocrystalline anisotropy, which competes with the dipolar energy, causes a strong modification of the spin configuration in the thin elements, depending on the shape, size and orientation of the structures. We investigate the magnetic switching processes and observe in triangular shaped elements a displacement of the vortex core along the easy axis for an external magnetic field applied close to the hard axis, which is well reproduced by micromagnetic simulations.

14.
Cytokine Growth Factor Rev ; 24(1): 23-40, 2013 Feb.
Article in English | MEDLINE | ID: mdl-22959722

ABSTRACT

Macrophage migration inhibitory factor (MIF) is increased in kidney and urine during kidney disease. MIF binds to and activates CD74 and chemokine receptors CXCR2 and CXCR4. CD74 is a protein trafficking regulator and a cell membrane receptor for MIF, D-dopachrome tautomerase (D-DT/MIF-2) and bacterial proteins. MIF signaling through CD74 requires CD44. CD74, CD44 and CXCR4 are upregulated in renal cells in diseased kidneys and MIF activation of CD74 in kidney cells promotes an inflammatory response. MIF or CXCR2 targeting protects from experimental kidney injury, CD44 deficiency modulates kidney injury and CXCR4 activation promotes glomerular injury. However, the contribution of MIF or MIF-2 to these actions of MIF receptors has not been explored. The safety and efficacy of strategies targeting MIF, CD74, CD44 and CXCR4 are under study in humans.


Subject(s)
Antigens, Differentiation, B-Lymphocyte/metabolism , Histocompatibility Antigens Class II/metabolism , Intramolecular Oxidoreductases/metabolism , Kidney Diseases/metabolism , Macrophage Migration-Inhibitory Factors/metabolism , Animals , Humans , Hyaluronan Receptors/metabolism , Inflammation , Intramolecular Oxidoreductases/urine , Macrophage Migration-Inhibitory Factors/urine , Mice , Receptors, CXCR4/metabolism , Receptors, Cell Surface/metabolism , Receptors, Interleukin-8B/metabolism
15.
Nefrología (Madr.) ; 32(6): 715-723, nov.-dic. 2012. ilus
Article in English | IBECS | ID: ibc-110487

ABSTRACT

There are no pathophysiolgical therapeutic approaches to acute kidney injury (AKI) and the mortality remains high. In addition chronic kidney disease (CKD) predisposes to AKI and AKI contributes to progression of CKD. Recently a transcriptomics approach unveiled a relationship between AKI, inflammation and the regulation of ageing. A transcriptomics analysis of experimental AKI revealed increased kidney expression of Fn14 and transmembrane chemokine CXCL16, as well as a decreased expression of the kidney-secreted anti-ageing hormone Klotho. Fn14 is the receptor for tumor necrosis factor-like weak inducer of apoptosis (TWEAK), a member of the TNF superfamily. In AKI kidneys there was a positive correlation between Fn14 and CXCL16 mRNA expression and an inverse correlation between Fn14 and Klotho mRNA. Tubular cells were the site of Fn14, CXCL16 and Klotho expression in vivo. Research on the relationships between these three molecules disclosed that TWEAK activation of Fn14 promoted inflammation through secretion of chemokines such as CXL16 in tubular cells in culture and in vivo. Furthermore, TWEAK activation of Fn14 decreased expression of Klotho mRNA and protein in culture and in vivo. Interestingly, both TWEAK activation of CXCL16 mRNA transcription and suppression of Klotho mRNA transcription were mediated by the NFκB transcription factor. In conclusion, TWEAK engagement of Fn14 is a central event promoting NFκB-mediated activation of inflammation pathways and suppression of anti-inflammatory/anti-ageing pathways. This information may influence future therapeutic approaches to AKI and inflammation/aging (AU)


No existen estrategias terapéuticas y fisiopatológicas para el fracaso renal agudo (FRA), por lo que los niveles de mortalidad continúan siendo elevados. Además, la enfermedad renal crónica (ERC) predispone a sufrir FRA y el FRA, a su vez, contribuye a que la ERC avance. Recientemente, una estrategia transcriptómica reveló una relación entre el FRA, la inflamación y la regulación del envejecimiento. Un análisis transcriptómico de modelos experimentales de FRA reveló un aumento de la expresión renal de Fn14 y la quimiocina transmembrana CXCL16, así como un descenso en la expresión de la hormona Klotho antienvejecimiento secretada por el riñón. Fn14 es el receptor de la citoquina tumor necrosis factor-like weak inducer of apoptosis (TWEAK), miembro de la superfamilia de factor de necrosis tumoral. En los riñones con FRA, existía una correlación positiva entre Fn14 y la expresión de ARNm de CXCL16 y una correlación inversa entre Fn14 y el ARNm de Klotho. El lugar donde se da la expresión in vivo de Fn14, CXCL16 y Klotho es las células tubulares. La investigación en las relaciones entre estas tres moléculas reveló que la activación de Fn14 por TWEAK provocó la inflamación mediante la secreción de quimiocinas como la CXCL16 en células tubulares, tanto en cultivo como in vivo. Además, la activación de Fn14 por TWEAK disminuyó la expresión de ARNm de Klotho y de proteína, en cultivo y in vivo. Curiosamente, tanto la activación TWEAK de la trascripción de ARNm de CXCL16 y la supresión de la trascripción de ARNm de Klotho estuvieron mediadas por el factor de transcripción NF-κB. Como conclusión, la unión de TWEAK y Fn14 es un elemento clave en promover de la activación mediada por NF-kB de las vías de inflamación y en la supresión de las vías antiinflamatorias y antienvejecimiento. Esta información puede influir en las futuras estrategias terapéuticas para el FRA y la inflamación/envejecimiento (AU)


Subject(s)
Humans , Acute Kidney Injury/genetics , Transcriptome/genetics , Aging/genetics , Inflammation/genetics , Renal Insufficiency, Chronic/physiopathology , Chemokine CXCL6/analysis , Membrane Proteins/analysis
16.
Nefrologia ; 32(6): 715-23, 2012.
Article in English | MEDLINE | ID: mdl-23093094

ABSTRACT

There are no pathophysiolgical therapeutic approaches to acute kidney injury (AKI) and the mortality remains high. In addition chronic kidney disease (CKD) predisposes to AKI and AKI contributes to progression of CKD. Recently a transcriptomics approach unveiled a relationship between AKI, inflammation and the regulation of ageing. A transcriptomics analysis of experimental AKI revealed increased kidney expression of Fn14 and transmembrane chemokine CXCL16, as well as a decreased expression of the kidney-secreted anti-ageing hormone Klotho. Fn14 is the receptor for tumor necrosis factor-like weak inducer of apoptosis (TWEAK), a member of the TNF superfamily. In AKI kidneys there was a positive correlation between Fn14 and CXCL16 mRNA expression and an inverse correlation between Fn14 and Klotho mRNA. Tubular cells were the site of Fn14, CXCL16 and Klotho expression in vivo. Research on the relationships between these three molecules disclosed that TWEAK activation of Fn14 promoted inflammation through secretion of chemokines such as CXL16 in tubular cells in culture and in vivo. Furthermore, TWEAK activation of Fn14 decreased expression of Klotho mRNA and protein in culture and in vivo. Interestingly, both TWEAK activation of CXCL16 mRNA transcription and suppression of Klotho mRNA transcription were mediated by the NFκB transcription factor. In conclusion, TWEAK engagement of Fn14 is a central event promoting NFκB-mediated activation of inflammation pathways and suppression of anti-inflammatory/anti-ageing pathways. This information may influence future therapeutic approaches to AKI and inflammation/aging.


Subject(s)
Acute Kidney Injury/genetics , Transcriptome , Acute Kidney Injury/etiology , Age Factors , Aging , Chemokine CXCL16 , Chemokines, CXC/genetics , Humans , Inflammation/complications , NF-kappa B/physiology , Receptors, Scavenger/genetics
17.
Adv Exp Med Biol ; 758: 333-42, 2012.
Article in English | MEDLINE | ID: mdl-23080180

ABSTRACT

The views presented in this article are the fruit of reflections and discussion with my colleagues at Valladolid and with the members of the Sleep Apnea Hypopnea Syndrome Group of the CIBERES (Spain). We have assembled the article in three sections. In the first one we provide a mechanistic description of obstructive sleep apnea (OSA) and all of its components, including the repetitive episodes of upper airways (UA) obstruction and accompanying hypoxic hypoxia, the respiratory efforts to fight and overcome the obstruction, and the sleep fragmentation due to the hypoxia-triggered arousal reactions, all events occurring during sleep hours with frequencies that might reach up >40-50 episodes/sleep hour. When OSA is accompanied by some of the elements of a big cohort of associated pathologies (vascular, metabolic, and neuropsychiatric) it conforms the obstructive sleep apnea syndrome (OSAS). The high frequency of OSAS in adults (>35 years old) and the costs in every regard of the treatment makes the syndrome a primary importance socio-sanitary problem. In the second section, we describe the experimental models of OSAS, basically the episodic repetitive hypoxic model described by Fletcher and coworkers in 1992, today named in short intermittent hypoxia (IH). From these lines, we want to call for some kind of consensus among researchers to lessen the dispersion of IH protocols. Finally, in the last section we intend to share our optimism with all ISAC members. The optimism is based on the recognition that carotid body (CB) chemoreceptors are critical elements of one of the main pathophysiologic loops in the genesis of OSAS. Therefore, we believe that all of us, as ISAC members, are well qualified to contribute in multidisciplinary research teams with well defined translational interests.


Subject(s)
Carotid Body/physiology , Hypoxia/physiopathology , Translational Research, Biomedical , Humans , Sleep Apnea, Obstructive/etiology , Sleep Apnea, Obstructive/physiopathology
18.
Minerva Med ; 103(4): 219-34, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22805616

ABSTRACT

Diabetic kidney disease (DKD) is the most frequent cause of end-stage renal disease in western countries. This implies that current methods based of renin angiotensin aldosterone system (RAAS) targeting for preventing, slowing or promoting regression of DKD are insufficient. Podocyte injury and albuminuria are thought to be key events in DKD. Indeed several DKD stages are recognized based on the magnitude of albuminuria. However, the spectrum of DKD has recently expanded, as lack of significant albuminuria is present in 30% of diabetics with kidney function impairment. This may result from the widespread use of drugs targeting the RAAS. However, it may also indicate that additional pathogenic factors contribute to renal function deterioration despite control of albuminuria. In this regard, double blockade of the RAAS is more effective in reducing albuminuria that blockade of a single component. However, clinical trials assessing double blockade for renal function preservation have been disappointing and raised safety issues. Non-biased -omics approaches have uncovered alternative therapeutic targets, including the cytokine TRAIL, the MIF receptor CD74 and the proapoptotic intracellular protein BASP1. In addition, urinary proteomics has uncovered a peptidomic fingerprint for DKD progression that precedes the onset of microalbuminuria. Studies are underway to validate this fingerprint for early treatment of high risk patients. Recent clinical trials suggest a potential role of bardoxolone methyl to improve renal function in advanced DKD, while trials of avosentan, pirfenidone, sulodexide and pyridoxamine have been disappointing and further data are needed for paricalcitol and vitamin D, newer generation endothelin receptor antagonists and pentoxifylline.


Subject(s)
Diabetic Nephropathies/drug therapy , Molecular Targeted Therapy/methods , Renal Agents/therapeutic use , Albuminuria/drug therapy , Albuminuria/etiology , Angiotensin-Converting Enzyme Inhibitors , Antigens, Differentiation, B-Lymphocyte , Biomarkers/analysis , Clinical Trials as Topic , Diabetic Nephropathies/complications , Disease Progression , Drug Therapy, Combination/methods , Histocompatibility Antigens Class II , Humans , Kidney Failure, Chronic/etiology , Membrane Proteins/antagonists & inhibitors , Nerve Tissue Proteins/antagonists & inhibitors , Podocytes/physiology , Proteomics/methods , Renin-Angiotensin System/drug effects , Repressor Proteins/antagonists & inhibitors , TNF-Related Apoptosis-Inducing Ligand/antagonists & inhibitors
19.
Rev. chil. pediatr ; 83(2): 161-169, abr. 2012. tab
Article in Spanish | LILACS | ID: lil-639752

ABSTRACT

Introduction: Limited information is available regarding factors contributing to exclusive breastfeeding until the sixth month. This information is needed to design appropriate policy interventions. Methods: A survey about socio-demographic characteristics, information received, onset and duration of breastfeeding and causes of weaning was applied. Factors associated with exclusive breastfeeding for 6 months were determined by multivariate logistic regression. Results: 256 mothers attending a public sector hospital and 158 mothers attending a private sector hospital responded to the survey. The following factors were higher in the private sector group: Education level, primiparity, cesarean sections and work outside the home (p < 0.02). 45.8 percent of mothers continued exclusive breastfeeding up to 6 months, with no difference seen between groups. The main causes of weaning were: maternal decision (27.2 percent), perceived hunger (24.1 percent), esthetic factors (17.3 percent) and child's illness (13.0 percent). Exclusive breastfeeding up to 6 months was associated with a previous successful breastfeeding (OR 5.4, 95 percent CI 2.2-13.2), female child (OR 5.5 CI 2.5-12.3), lower maternal education (OR 5.4 CI 2.4-11.7) and public health system (OR 2.1 CI 1.0-4.5). Conclusion: Weaning is often associated with maternal perceptions rather than objective data. Socio-demographic variables influence successful prolonged breastfeeding. Better education in health factors and breastfeeding might improve this situation.


Introducción: Existe limitada información de los factores que contribuyen a una lactancia materna exclusiva hasta el sexto mes, datos necesarios para diseñar adecuadas políticas de intervención. Pacientes y Método: Estudio de corte transversal. Se aplicó una encuesta sobre características socio-demográficas, información recibida, inicio y duración de la lactancia y causas de destete. Por regresiones logísticas multivariadas se determinaron factores asociados a lactancia exclusiva de 6 meses. Resultados: 256 madres del sector público y 158 del sector privado fueron incluidas. Se observó mayor escolaridad, primiparidad, cesáreas y trabajo fuera del hogar en sistema privado (p < 0,02); 45,8 por ciento de madres mantuvo lactancia exclusiva hasta 6 meses, sin diferencias entre grupos. Principales causas de destete: decisión materna (27,2 por ciento), percepción de hambre (24,1 por ciento), factores estéticos (17,3 por ciento) y enfermedad del niño (13,0 por ciento). La lactancia exclusiva hasta los 6 meses se asoció con una lactancia previa exitosa (OR 5,4, 95 por ciento IC 2,2-13,2) sexo femenino del hijo (OR 5,5, IC 2,5-12,3), menor escolaridad materna (OR 5,4, IC 2,4-11,7) y sistema público de salud (OR 2,1, IC 1,0-4,5). Conclusión: El destete muchas veces está relacionado con percepciones maternas más que con datos objetivos. Variables socio-demográficas influyen en lactancia exitosa. Mayor educación en controles de salud y clínicas de lactancia mejorarían esta situación.


Subject(s)
Humans , Female , Infant , Breast Feeding , Maternal Behavior , Weaning , Chile , Cross-Sectional Studies , Data Collection , Private Sector , Public Sector , Socioeconomic Factors , Time Factors
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