Mitochondria-Targeted Antioxidants: Future Perspectives in Kidney Ischemia Reperfusion Injury

Kidney ischemia/reperfusion injury emerges in various clinical settings as a great problem complicating the course and outcome. Ischemia/reperfusion injury is still an unsolved puzzle with a great diversity of investigational approaches, putting the focus on oxidative stress and mitochondria. Mitochondria are both sources and targets of ROS. They participate in initiation and progression of kidney ischemia/reperfusion injury linking oxidative stress, inflammation, and cell death. The dependence of kidney proximal tubule cells on oxidative mitochondrial metabolism makes them particularly prone to harmful effects of mitochondrial damage. The administration of antioxidants has been used as a way to prevent and treat kidney ischemia/reperfusion injury for a long time. Recently a new method based on mitochondria-targeted antioxidants has become the focus of interest. Here we review the current status of results achieved in numerous studies investigating these novel compounds in ischemia/reperfusion injury which specifically target mitochondria such as MitoQ, Szeto-Schiller (SS) peptides (Bendavia), SkQ1 and SkQR1, and superoxide dismutase mimics. Based on the favorable results obtained in the studies that have examined myocardial ischemia/reperfusion injury, ongoing clinical trials investigate the efficacy of some novel therapeutics in preventing myocardial infarct. This also implies future strategies in preventing kidney ischemia/reperfusion injury

Changes in nano-mechanical properties of human epidermal cornified cells in children with atopic dermatitis

Background: Impaired skin barrier is an important etiological factor in atopic dermatitis (AD). The structural protein filaggrin (FLG) plays a major role in maintenance of the competent skin barrier and its deficiency is associated with enhanced susceptibility to mechanical injury. Here we examined biomechanical characteristics of the corneocytes in children with AD and healthy controls. Methods: We recruited 20 children with AD and 7 healthy children. They were genotyped for filaggrin gene ( FLG) loss-of-function mutations. Stratum corneum was collected from clinically unaffected skin by adhesive tapes. Cell stiffness (apparent elastic modulus, Ea) was determined by atomic force microscopy and filaggrin degradation products (NMF) by liquid chromatography. Skin barrier function was assessed through trans-epidermal water loss (TEWL) and disease severity by the SCORing Atopic Dermatitis (SCORAD) tool. Results: Corneocytes collected from AD patients showed a decreased elastic modulus which was strongly correlated with NMF and TEWL, but not with SCORAD. As compared with healthy controls, AD patients had reduced TEWL and NMF levels regardless of FLG mutations. NMF was strongly correlated with TEWL. Conclusion: Our findings demonstrate that AD patients have decreased corneocyte stiffness which correlates with reduced levels of filaggrin degradation products, NMF and skin barrier function. Altered mechanical properties of the corneocytes likely contribute to the loss of mechanical integrity of the SC and to reduced skin barrier function in AD

Topical Corticosteroids Normalize both Skin and Systemic Inflammatory Markers in Infant Atopic Dermatitis

Background: Atopic dermatitis (AD) is the most common inflammatory skin disease. It is highly heterogeneous in clinical presentation, treatment response, disease trajectory and associated atopic comorbidities. Immune biomarkers are dysregulated in skin and peripheral blood. Aims: We used noninvasive skin and peripheral biomarkers to observe the effects of real-world topical corticosteroid (TCS) treatment in infants with AD, by measuring skin and blood biomarkers before and after therapy. Methods: Seventy-four treatment-naïve infants with AD underwent 6 weeks of TCS treatment. Stratum corneum (SC) and plasma blood biomarkers as well as SC natural moisturizing factor (NMF) were measured before and after TCS therapy. Immune markers included innate, T helper (Th)1 and Th2 immunity, angiogenesis, and vascular factors. AD severity was assessed by the Scoring Atopic Dermatitis index, and skin barrier function by transepidermal water loss (TEWL). Twenty healthy infants were recruited as controls. Results: TCS therapy predictably led to improvement in disease severity. Levels of immune markers in the skin and in the peripheral blood showed significant change from baseline, though most did not reach healthy control levels. The most prominent change from baseline in the SC was in markers of innate immune activation, interleukin (IL)-18, IL-8 and IL-1α, and the Th2 chemokines C-C motif chemokine (CCL)17 and CCL22. In blood, the largest changes were in Th2-skewed biomarkers: CCL17, IL-13, CCL22, IL-5, and CCL26. TEWL decreased after therapy; no significant changes from baseline were found for NMF. Conclusions: The profound impact of topical therapy on systemic biomarkers suggests that the skin compartment generates a major component of dysregulated systemic cytokines in infant AD. There may be long-term beneficial effects of correcting systemic immune dysregulation through topical therapy

In vitro percutaneous penetration and characterization of silver from silver-containing textiles

The objective of this study was to determine the in vitro percutaneous penetration of silver and characterize the silver species released from textiles in different layers of full thickness human skin. For this purpose, two different wound dressings and a garment soaked in artificial sweat were placed in the donor compartments of Franz cells for 24 hours. The concentration of silver in the donor phase and in the skin was determined by an electrothermal atomic absorption spectrometer (ET-AAS) and by inductively coupled plasma mass spectrometer (ICP-MS). The characterization of silver species in the textiles and in the skin layers was made by scanning electron microscopy with integrated energy dispersive X-ray spectroscopy (SEM-EDX). Additionally, the size distribution of silver nanoparticles in the textiles was performed by atomic force microscopy (AFM). On the surface of all investigated materials, silver nanoparticles of different size and morphology were found. Released silver concentrations in the soaking solutions (ie, exposure concentration) ranged from 0.7 to 4.7 μg/mL (0.6–4.0 μg/cm2), fitting the bactericidal range. Silver and silver chloride aggregates at sizes of up to 1 μm were identified both in the epidermis and dermis. The large size of these particles suggests that the aggregation occurred in the skin. The formation of these aggregates likely slowed down the systemic absorption of silver. Conversely, these aggregates may form a reservoir enabling prolonged release of silver ions, which might lead to local effects

Choreography Strategies in Women’s Artistic Gymnastics Floor Routines across Five Olympic Games

Routine compositions are an indicator of an exercising trend in a particular Olympic cycle in artistic gymnastics. The pri- mary aim of the current study was to identify which acrobatic and dance elements significantly influence specific scores throughout five different Olympic Games (OG) in elite female artistic gymnasts: finalists of OG 2000-2016. A total of 40 female competitors, participants of floor apparatus finals competitions, were subjects of this study. The results identi- fied the following: 1) at OG 2000, an under-sensitive scoring system did not allow the extraction of individual elements that significantly contributed to a specific score; 2) the performance of acrobatic elements from the highest difficulty groups had a significant impact in OG 2004; 3) At OG 2008, exercises comprising slightly easier elements, performed technically and aesthetically correctly, scored better than exercises comprising elements of higher difficulty values per- formed with specific technical and/or aesthetic errors; 4) at OG 2012, the performance of the most difficult acrobatic el- ements without technical errors was the key to a better result; 5) quality performance of the greatest difficulty acrobatic elements, as well as the performance of the highest bonuses between the acrobatic and dance elements was the key to success at OG 2016. The results of this research are possible indicators of future floor compositions in OG 2020 and provide guidance to everyone involved in the long-term planning and programming process of future floor finalists

EL TERRITORIO COMO PUENTE ENTRE LA CULTURA Y LA POLÍTICA, PARTE II. EL PENSAMIENTO DE FEDERICO A. DAUS 1922-1957

Se presenta un recorrido por el pensamiento de Federico A. Daus a través de su obra escrita, en especial hasta la aparición de “Geografía y unidad argentina”, su obra cumbre. El orden cronológico provee un método preliminar para comenzar a distinguir componentes. Desde el comienzo puede verificarse un interés por el territorio como campo de especulación práctica. Luego su producción se adapta a las líneas humanistas de Museo Etnográfico de la Universidad de Buenos Aires. En la Universidad Nacional de La Plata profundiza la vertiente de la política de recursos naturales, a través de la geografía regional. Previo a la vinculación con el peronismo, Daus compone dos de sus piezas integrales, la Geografía de la República Argentina, publicada en España, y la primera parte de su Geografía de la Argentina, destinada a la enseñanza. Se produce una pausa en su producción hasta la aparición de “Geografía y unidad argentina”, un planteo sobre el rol del territorio en la conformación de la Argentina. La vertiente práctica es abordada nuevamente, años después, a través de la temática del desarrollo, como combinación entre el perfil académico y cultural y la búsqueda de realizar una contribución a la vida del país a través del territorio.A summary of Federico Daus’ thinking is presented through his written work, in particular that before the publication of “Geografía y unidad argentina”, his most distinctive piece. The chronological order provides a preliminary method to outline a set of main issues. An interest on territory as a field for applied speculation may be recognized on his most early contributions. Afterwards, his work adapts to the humanistic lines of the Museo Etnográfico of the University of Buenos Aires. At University of La Plata he further develops a political understanding of natural resources through regional geography. Before his engagement with the peronist government Daus composes two of his most comprehensive works, the “Geografía de la República Argentina”, published in Spain, and the first volume of his “Geografía de la Argentina”, intended forsecondary school teaching. His production comes to a complete stop until “Geografía y unidad argentina”, an analysis of the role of territory in Argentina’s conformation. The prospective point of view is addressed one again in the following years through the idea of development, as a combination of cultural academic inputs and the search of making a contribution to national life through territory

Systemic and stratum corneum biomarkers of severity in infant atopic dermatitis include markers of innate and T helper cell-related immunity and angiogenesis

BACKGROUND: Biomarkers of atopic dermatitis (AD) are largely lacking, especially in infant AD. Those that have been examined to date have focused mostly on serum cytokines with few on non-invasive biomarkers in the skin. OBJECTIVES: We aimed to explore biomarkers obtainable from non-invasive sampling of infant skin. We compared these to plasma biomarkers and structural and functional measures of the skin barrier. METHODS: We recruited 100 infants at first presentation with AD, who were treatment naïve to topical or systemic anti-inflammatory therapies and 20 healthy children. We sampled clinically unaffected skin by tape stripping the stratum corneum (SC). Multiple cytokines and chemokines and natural moisturizing factors (NMF) were measured in the SC and plasma. We recorded disease severity and skin barrier function. RESULTS: 19 SC and 12 plasma biomarkers showed significant difference between healthy and AD skin. Some biomarkers were common to both the SC and plasma, and others were compartment-specific. Identified biomarkers of AD severity included Th2 skewed markers (IL-13, CCL17, CCL22, IL-5), markers of innate activation (IL-18, Il-1α, IL1β, CXCL8), angiogenesis (Flt-1, VEGF) and others (sICAM-1, vCAM-1, IL-16, IL-17A). CONCLUSIONS: We identified clinically relevant biomarkers of AD, including novel markers, easily sampled and typed in infants. These markers may provide objective assessment of disease severity and suggest new therapeutic targets, or response measurement targets for AD. Future studies will be required to determine if these biomarkers, seen in very early AD, can predict disease outcomes or comorbidities