The protective effect of 1400W against ischaemia and reperfusion injury is countered by transient medullary kidney endothelial dysregulation.

Renal ischaemia and reperfusion (I/R) is caused by a sudden temporary impairment of the blood flow. I/R is a prevalent cause of acute kidney injury. As nitric oxide generated by inducible nitric oxide synthase (iNOS) has detrimental effects during I/R, the pharmacological blockade of iNOS has been proposed as a potential strategy to prevent I/R injury. The aim of this study was to improve the understanding of 1400W (an iNOS inhibitor) on renal I/R as a pharmacological strategy against kidney disease. BALB/c mice received 30 min of bilateral ischaemia, followed by 48 h or 28 days of reperfusion. Vehicle or 1400W (10 mg/kg) was administered 30 min before inducing ischaemia. We found that after 48 h of reperfusion 1400W decreased the serum creatinine, blood urea nitrogen, neutrophil gelatinase-associated lipocalin and proliferating cell nuclear antigen 3 in the I/R animals. Unexpectedly, we observed mRNA upregulation of genes involved in kidney injury, cell-cycle arrest, inflammation, mesenchymal transition and endothelial activation in the renal medulla of sham animals treated with 1400W. We also explored if 1400W promoted chronic kidney dysfunction 28 days after I/R and did not find significant alterations in renal function, fibrosis, blood pressure or mortality. The results provide evidence that 1400W may have adverse effects in the renal medulla. Importantly, our data point to 1400W-induced endothelial dysfunction, establishing therapeutic limitations for its use. KEY POINTS: Acute kidney injury is a global health problem associated with high morbidity and mortality. The pharmacological blockade of inducible nitric oxide synthase (iNOS) has been proposed as a potential strategy to prevent AKI induced by ischaemia and reperfusion (I/R). Our main finding is that 1400W, a selective and irreversible iNOS inhibitor with low toxicity that is proposed as a therapeutic strategy to prevent kidney I/R injury, produces aberrant gene expression in the medulla associated to tissue injury, cell cycle arrest, inflammation, mesenchymal transition and endothelial activation. The negative effect of 1400W observed in the renal medulla at 48 h from drug administration, is transient as it did not translate into a chronic kidney disease condition.

Design of Sustainable Aluminium-Based Feedstocks for Composite Extrusion Modelling (CEM).

Additive manufacturing (AM) has become one of the most promising manufacturing techniques in recent years due to the geometric design freedom that this technology offers. The main objective of this study is to explore Composite Extrusion Modelling (CEM) with aluminium as an alternative processing route for aluminium alloys. This process allows for working with pellets that are deposited directly, layer by layer. The aim of the technique is to obtain aluminium alloy samples for industrial applications with high precision, without defects, and which are processed in an environmentally friendly manner. For this purpose, an initial and preliminary study using powder injection moulding (PIM), necessary for the production of samples, has been carried out. The first challenge was the design of a sustainable aluminium-based feedstock. The powder injection moulding technique was used as a first approach to optimise the properties of the feedstock through a combination of water-soluble polymer, polyethyleneglycol (PEG), and cellulose acetate butyrate (CAB) wich produces low CO2 emissions. To do this, a microstructural characterisation was carried out and the critical solid loading and rheological properties of the feedstocks were studied. Furthermore, the debinding conditions and sintering parameters were adjusted in order to obtain samples with the required density for the following processes and with high geometrical accuracy. In the same way, the printing parameters were optimised for proper material deposition.

The Antimicrobial Activity of Micron-Thin Sol-Gel Films Loaded with Linezolid and Cefoxitin for Local Prevention of Orthopedic Prosthesis-Related Infections.

Orthopedic prosthesis-related infections (OPRI) are an essential health concern. OPRI prevention is a priority and a preferred option over dealing with poor prognosis and high-cost treatments. Micron-thin sol-gel films have been noted for a continuous and effective local delivery system. This study aimed to perform a comprehensive in vitro evaluation of a novel hybrid organic-inorganic sol-gel coating developed from a mixture of organopolysiloxanes and organophosphite and loaded with different concentrations of linezolid and/or cefoxitin. The kinetics of degradation and antibiotics release from the coatings were measured. The inhibition of biofilm formation of the coatings against Staphylococcus aureus, S. epidermidis, and Escherichia coli strains was studied, as well as the cell viability and proliferation of MC3T3-E1 osteoblasts. The microbiological assays demonstrated that sol-gel coatings inhibited the biofilm formation of the evaluated Staphylococcus species; however, no inhibition of the E. coli strain was achieved. A synergistic effect of the coating loaded with both antibiotics was observed against S. aureus. The cell studies showed that the sol-gels did not compromise cell viability and proliferation. In conclusion, these coatings represent an innovative therapeutic strategy with potential clinical use to prevent staphylococcal OPRI.

Influence of Addition of Antibiotics on Chemical and Surface Properties of Sol-Gel Coatings.

Infection is one of the most common causes that leads to joint prosthesis failure. In the present work, biodegradable sol-gel coatings were investigated as a promising controlled release of antibiotics for the local prevention of infection in joint prostheses. Accordingly, a sol-gel formulation was designed to be tested as a carrier for 8 different individually loaded antimicrobials. Sols were prepared from a mixture of MAPTMS and TMOS silanes, tris(tri-methylsilyl)phosphite, and the corresponding antimicrobial. In order to study the cross-linking and surface of the coatings, a battery of examinations (Fourier-transform infrared spectroscopy, solid-state 29Si-NMR spectroscopy, thermogravimetric analysis, SEM, EDS, AFM, and water contact angle, thickness, and roughness measurements) were conducted on the formulations loaded with Cefoxitin and Linezolid. A formulation loaded with both antibiotics was also explored. Results showed that the coatings had a microscale roughness attributed to the accumulation of antibiotics and organophosphites in the surface protrusions and that the existence of chemical bonds between antibiotics and the siloxane network was not evidenced.

A New Antifungal-Loaded Sol-Gel Can Prevent Candida albicans Prosthetic Joint Infection.

Fungal PJI is one of the most feared complications after arthroplasty. Although a rare finding, its high associated morbidity and mortality makes it an important object of study. The most frequent species causing fungal PJI is C. albicans. New technology to treat this type of PJI involves organic-inorganic sol-gels loaded with antifungals, as proposed in this study, in which anidulafungin is associated with organophosphates. This study aimed to evaluate the efficacy of an anidulafungin-loaded organic-inorganic sol-gel in preventing prosthetic joint infection (PJI), caused by Candida albicans using an in vivo murine model that evaluates many different variables. Fifty percent (3/6) of mice in the C. albicans-infected, non-coated, chemical-polished (CP)-implant group had positive culture and 100% of the animals in the C. albicans-infected, anidulafungin-loaded, sol-gel coated (CP + A)-implant group had a negative culture (0/6) (p = 0.023). Taking the microbiology and pathology results into account, 54.5% (6/11) of C. albicans-infected CP-implant mice were diagnosed with a PJI, whilst only 9.1% (1/11) of C. albicans-infected CP + A-implant mice were PJI-positive (p = 0.011). No differences were observed between the bone mineral content and bone mineral density of noninfected CP and noninfected CP + A (p = 0.835, and p = 0.181, respectively). No histological or histochemical differences were found in the tissue area occupied by the implant among CP and CP + A. Only 2 of the 6 behavioural variables evaluated exhibited changes during the study: limping and piloerection. In conclusion, the anidulafungin-loaded sol-gel coating showed an excellent antifungal response in vivo and can prevent PJI due to C. albicans in this experimental model.

A Biodegradable Antifungal-Loaded Sol-Gel Coating for the Prevention and Local Treatment of Yeast Prosthetic-Joint Infections.

Fungal prosthetic-joint infections are rare but devastating complications following arthroplasty. These infections are highly recurrent and expose the patient to the development of candidemia, which has high mortality rates. Patients with this condition are often immunocompromised and present several comorbidities, and thus pose a challenge for diagnosis and treatment. The most frequently isolated organisms in these infections are Candida albicans and Candida parapsilosis, pathogens that initiate the infection by developing a biofilm on the implant surface. In this study, a novel hybrid organo-inorganic sol-gel coating was developed from a mixture of organopolysiloxanes and organophosphite, to which different concentrations of fluconazole or anidulafungin were added. Then, the capacity of these coatings to prevent biofilm formation and treat mature biofilms produced by reference and clinical strains of C. albicans and C. Parapsilosis was evaluated. Anidulafungin-loaded sol-gel coatings were more effective in preventing C. albicans biofilm formation, while fluconazole-loaded sol-gel prevented C. parapsilosis biofilm formation more effectively. Treatment with unloaded sol-gel was sufficient to reduce C. albicans biofilms, and the sol-gels loaded with fluconazole or anidulafungin slightly enhanced this effect. In contrast, unloaded coatings stimulated C. parapsilosis biofilm formation, and loading with fluconazole reduced these biofilms by up to 99%. In conclusion, these coatings represent a novel therapeutic approach with potential clinical use to prevent and treat fungal prosthetic-joint infections.

A New Antibiotic-Loaded Sol-Gel can Prevent Bacterial Intravenous Catheter-Related Infections.

The aim of this study was to evaluate the effectiveness of a moxifloxacin-loaded organic-inorganic sol-gel (A50) by locally preventing the catheter-related bloodstream infection (CRBSI) provoked by Staphylococcus epidermidis (S. epidermidis) and the effect resulting from its hydrolytic degradation on coagulation by using a rabbit in-vivo model. A50 coating can completely inhibit growth and would locally prevent CRBSI provoked by S. epidermidis. None of the coagulation blood parameters showed a significant difference constant over time between the control catheter group and the A50-coated catheter group, despite the visible silica release resulting from physiological A50 sol-gel degradation detected in serum at least during the first week. At pathological level, foreign body reaction was present in both of types of catheter, and it was characterized by the presence of macrophages and foreign body giant cell. However, this reaction was different in each group: the A50-coated catheter group showed a higher inflammation with histiocytes, which were forming granuloma-like aggregates with an amorphous crystalline material inside, accompanied by other inflammatory cells such as plasma cells, lymphocytes and mast cells. In conclusion, A50 coating a venous catheter showed excellent bactericidal anti-biofilm response since it completely inhibited S. epidermidis biofilm development and, far from showing procoagulant effects, showed slightly anticoagulant effects.

A New Antibiotic-Loaded Sol-Gel Can Prevent Bacterial Prosthetic Joint Infection: From in vitro Studies to an in vivo Model.

The aim of this study was to evaluate the effect of a moxifloxacin-loaded organic-inorganic sol-gel with different antibiotic concentration in the in vitro biofilm development and treatment against Staphylococcus aureus, S. epidermidis, and Escherichia coli, cytotoxicity and cell proliferation of MC3T3-E1 osteoblasts; and its efficacy in preventing the prosthetic joint infection (PJI) caused by clinical strains of S. aureus and E. coli using an in vivo murine model. Three bacterial strains, S. epidermidis ATCC 35984, S. aureus 15981, and, E. coli ATCC 25922, were used for microbiological studies. Biofilm formation was induced using tryptic-soy supplemented with glucose for 24 h, and then, adhered and planktonic bacteria were estimated using drop plate method and absorbance, respectively. A 24-h-mature biofilm of each species growth in a 96-well plate was treated for 24 h using a MBECTM biofilm Incubator lid with pegs coated with the different types of sol-gel, after incubation, biofilm viability was estimated using alamrBlue. MC3T3-E1 cellular cytotoxicity and proliferation were evaluated using CytoTox 96 Non-Radioactive Cytotoxicity Assay and alamarBlue, respectively. The microbiological studies showed that sol-gel coatings inhibited the biofilm development and treated to a mature biofilm of three evaluated bacterial species. The cell studies showed that the sol-gel both with and without moxifloxacin were non-cytotoxic and that cell proliferation was inversely proportional to the antibiotic concentration containing by sol-gel. In the in vivo study, mice weight increased over time, except in the E. coli-infected group without coating. The most frequent symptoms associated with infection were limping and piloerection; these symptoms were more frequent in infected groups with non-coated implants than infected groups with coated implants. The response of moxifloxacin-loaded sol-gel to infection was either total or completely absent. No differences in bone mineral density were observed between groups with coated and non-coated implants and macrophage presence lightly increased in the bone grown directly in contact with the antibiotic-loaded sol-gel. In conclusion, moxifloxacin-loaded sol-gel coating is capable of preventing PJI caused by both Gram-positive and Gram-negative species.

Biocompatibility and Corrosion Protection Behaviour of Hydroxyapatite Sol-Gel-Derived Coatings on Ti6Al4V Alloy.

The aim of this work was to prepare hydroxyapatite coatings (HAp) by a sol-gel method on Ti6Al4V alloy and to study the bioactivity, biocompatibility and corrosion protection behaviour of these coatings in presence of simulated body fluids (SBFs). Thermogravimetric/Differential Thermal Analyses (TG/DTA) and X-ray Diffraction (XRD) have been applied to obtain information about the phase transformations, mass loss, identification of the phases developed, crystallite size and degree of crystallinity of the obtained HAp powders. Fourier Transformer Infrared Spectroscopy (FTIR) has been utilized for studying the functional groups of the prepared structures. The surface morphology of the resulting HAp coatings was studied by Scanning Electron Microscopy (SEM). The bioactivity was evaluated by soaking the HAp-coatings/Ti6Al4V system in Kokubo's Simulated Body Fluid (SBF) applying Inductively Coupled Plasma (ICP) spectrometry. 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and Alamar blue cell viability assays were used to study the biocompatibility. Finally, the corrosion behaviour of HAp-coatings/Ti6Al4V system was researched by means of Electrochemical Impedance Spectroscopy (EIS). The obtained results showed that the prepared powders were nanocrystalline HAp with little deviations from that present in the human bone. All the prepared HAp coatings deposited on Ti6Al4V showed well-behaved biocompatibility, good bioactivity and corrosion protection properties.

Evaluación clínica abierta multicéntrica no aleatorizada y prospectiva de la efectividad de una emulsión a base de ácidos grasos hiperoxigenados, Aloe barbadensis y Mimosa tenuiflora (Mepentol® Leche) en diferentes tipos de pacientes con riesgo de ulceración / Multicentric prospective non randomized open clinical evaluation of the efficacy of an emulsion based on hyperoxigenated fatty acids Aloe barbadensis and Mimosa tenuiflora (Mepentol® Leche) in different types of patients with risk of ulceration

Las úlceras de la extremidad inferior suponen un grave problema sanitario que afecta a un gran número de pacientes, constituyendo por ello un gran reto de trabajo para los profesionales de la salud. Los ácidos grasos hiperoxigenados (AGHO) han demostrado tener eficacia en la prevención de este tipo de úlceras. Gracias a los buenos resultados obtenidos en un estudio previo, nos planteamos seguir evaluando la efectividad del producto Mepentol® Leche, una emulsión a base de ácidos grasos hiperoxigenados, Aloe barbadensis y Mimosa tenuiflora, en el cuidado de la piel y alivio de los síntomas en pacientes con este problema, pero ampliando el tamaño de la muestra y centrándonos en pacientes diabéticos junto con otras enfermedades concomitantes. Además, en este estudio se ha implicado a profesionales de enfermería de seis provincias: Almería, Alicante, Granada, Sevilla, Málaga y Ceuta. De nuevo con este estudio, realizado en un total de 2.145 pacientes, hemos demostrado que ningún paciente ha ulcerado durante el tiempo de seguimiento y tratamiento con Mepentol® Leche y que su aplicación sistemática mejora claramente los síntomas previos a la aparición de úlceras, evitando la sequedad cutánea, reduciendo el prurito, escozor, dolor y eccema, y devolviendo la piel de estos pacientes a su coloración normal (AU)

The lower extremity wounds are a serious health problem that affects a large number of patients, thereby assuming a great challenge to work for health professionals. Hyperoxygenated fatty acids (AGHO), have demonstrated efficacy in the prevention of this type of ulcers. Thanks to the good results obtained in a previous study, we plan to continue evaluating the effectiveness of Mepentol® Leche, an emulsion-based hyper-oxygenated fatty acids, Aloe barbadensis and Mimosa tenuiflora in skin care and relief of symptoms, in patients with this problem, but expanding the sample size and focusing on diabetic patients with concomitant diseases. Also in this study have been involving nurses in six provinces: Almería, Alicante, Granada, Seville, Malaga and Ceuta. Again with this study, a total of 2,145 patients, we demonstrated that no patient has ulcerated during the follow-up and treatment with Mepentol® Leche and its systematic application significantly improves the symptoms before the onset of ulcers, preventing dryness skin, reducing itching, burning, pain and eczema, and returning the skin of these patients to their normal color (AU)

[Prevention of vascular ulcers and diabetic foot. Non-randomized open clinical evaluation on the effectiveness of "Mepentol Leche"]. / Prevención de ulceras vasculares y pie diabético. Evaluación clínica abierta no aleatorizada sobre la efectividad de Mepentol Leche.

INTRODUCTION: Vascular ulcers and diabetic foot ulcers present a health serious problem which affects a large number of patients, creating a major challenge for health professionals. Hyper-oxygenated fatty acid dressings have proven to be effective thanks to their favorable action on the skin in three ways: increasing the microcirculation of the blood, promoting the renovation of the epidermic cells, and notably increasing cutaneous hydration. OBJECTIVE: Evaluate the effectiveness of Mepentol Leche, an emulsion based on Hyper-oxygenated fatty acids, Aloe barbadensis and Mimosa tenuiflora, used to treat the skin and alleviate symptoms in patients who suffer from vascular ulcers and diabetic foot ulcers. METHODS: Clinical evaluation carried out between June 2004 and December 2005. 195 patients were studied. The parameters for inclusion in this study were 32.82% for venous pathology 35.90% for skin care, 26.67% due to arterial pathology, and 4.62% for a lymphatic pathology. These patients were evaluated over a one month period and each had a follow-up by means of a data collection file. The guideline to apply this product was twice a day and always over integral skin. The effectiveness of this product has been established based on these epigraphs: symptoms of itching, smarting and pain, and skin conditions: color, dryness, edema, maceration, rashes, and desquamation. RESULTS: Not one patient developed new lesions in healthy skin protected by Mepentol Leche. Symptoms linked to this pathology saw improvements in these percents: itching 96%, smarting 93%, and pain 96%, and skin conditions: color 100%, edema 90%, maceration 96%, rashes 92%, and desquamation 100%. Health professionals' evaluation of this product has been highly favorable in regards to ease of use, tolerance, absorption, and ease of application. CONCLUSIONS: This study showed the benefits in applying this product systematically to alleviate the symptoms prior to the appearance of ulcers, thus avoiding skin dryness and reducing itching, smarting, pain and eczema while returning normal color to the skin.

Prevención de úlceras vasculares y pie diabético. Evaluación clínica abierta no aleatorizada sobre la efectividad de Mepentol Leche / Prevention of vascular ulcers and diabetic foot. Non-randomized open clinical evaluation on the effectiveness of "Mepentol Leche"

Introducción: las úlceras vasculares y úlceras de pie diabético constituyen un grave problema sanitario que afecta a un gran número de pacientes, suponiendo por ello un gran reto de trabajo para los profesionales de la salud. Los ácidos grasos hiperoxigenados (AGHO) han demostrado tener eficacia gracias a su acción favorable sobre la piel en tres puntos: aumentando la microcirculación sanguínea, impulsando la renovación celular epidérmica y mejorando notablemente la hidratación cutánea. Objetivo: evaluar la eficacia del producto Mepentol Leche, una emulsión a base de ácidos grasos hiperoxigenados, Aloe barbadensis y Mimosa tenuiflora, en el cuidado de la piel y el alivio de los síntomas, en pacientes con úlceras vasculares y úlceras de pie diabético. Métodos: evaluación clínica realizada entre junio de 2004 a diciembre de 2005. Se estudia un total de 195 pacientes. Los parámetros de inclusión han sido: por patología venosa (32,82%), cuidado de la piel (35,90%), patología arterial (26,67%) y patología linfática (4,62%). Los pacientes han sido evaluados durante un mes y se ha realizado un seguimiento de cada uno de ellos mediante una ficha de recogida de datos. La pauta de aplicación del producto ha sido de dos veces al día y siempre en piel íntegra. La efectividad del producto se ha establecido en base a los siguientes epígrafes: sintomatología (prurito, escozor y dolor) y condiciones de la piel (coloración, sequedad, edema, maceración, eritema y descamación). Resultados: ningún paciente ha desarrollado nuevas lesiones en la piel sana protegida con Mepentol Leche. Los síntomas asociados mejoran en: prurito (96%), escozor (93%), dolor (96%), coloración de la piel (100%), edema (90%), maceración (96%), eritema (92%) y descamación (100%). La valoración del producto por parte de los profesionales ha sido muy buena respecto a la comodidad, tolerabilidad, absorción y facilidad de aplicación. Conclusiones: se demuestran los beneficios de su aplicación sistemática en el alivio de los síntomas previos a la aparición de úlceras, evitando la sequedad cutánea, reduciendo el prurito, escozor, dolor y eczema, y devolviendo la piel a su coloración normal

INTRODUCTION: Vascular ulcers and diabetic foot ulcers present a health serious problem which affects a large number of patients, creating a major challenge for health professionals. Hyper-oxygenated fatty acid dressings have proven to be effective thanks to their favorable action on the skin in three ways: increasing the microcirculation of the blood, promoting the renovation of the epidermic cells, and notably increasing cutaneous hydration. OBJECTIVE: Evaluate the effectiveness of Mepentol Leche, an emulsion based on Hyper-oxygenated fatty acids, Aloe barbadensis and Mimosa tenuiflora, used to treat the skin and alleviate symptoms in patients who suffer from vascular ulcers and diabetic foot ulcers. METHODS: Clinical evaluation carried out between June 2004 and December 2005. 195 patients were studied. The parameters for inclusion in this study were 32.82% for venous pathology 35.90% for skin care, 26.67% due to arterial pathology, and 4.62% for a lymphatic pathology. These patients were evaluated over a one month period and each had a follow-up by means of a data collection file. The guideline to apply this product was twice a day and always over integral skin. The effectiveness of this product has been established based on these epigraphs: symptoms of itching, smarting and pain, and skin conditions: color, dryness, edema, maceration, rashes, and desquamation. RESULTS: Not one patient developed new lesions in healthy skin protected by Mepentol Leche. Symptoms linked to this pathology saw improvements in these percents: itching 96%, smarting 93%, and pain 96%, and skin conditions: color 100%, edema 90%, maceration 96%, rashes 92%, and desquamation 100%. Health professionals' evaluation of this product has been highly favorable in regards to ease of use, tolerance, absorption, and ease of application. CONCLUSIONS: This study showed the benefits in applying this product systematically to alleviate the symptoms prior to the appearance of ulcers, thus avoiding skin dryness and reducing itching, smarting, pain and eczema while returning normal color to the skin

Cromatina sexual en el recien nacido / Sexual chromatine in the newborn

Se determina el sexo nuclear a ciegas, mientras raspado de la mucosa bucal y coloración con acetorceína en 400 recién nacidos a término normal, en las primeras 72 horas de vida. Se encuentra que 228 eran cromatina-negativa y 172 cromatina-positiva. No se observó divergencia entre el sexo nuclear y el fenotipo. En las 172 recién nacidas normales, la frecuencia de cuerpos de Barr fue de 16.4 por ciento con una desviación estándar de ± 8.1. Se compara esta cifra con la obtenida en 100 controles normales, que fue de 33 por ciento con una desviación estándar de ± 10,1. La diferencia es notable (t=14,12<0.05=. Se considera por tanto, en nuestras salas de recién nacidos, que la prueba del sexo nuclear obtenida de la mucosa bucal es útil y confiable, aunque hay que tener en cuenta que los valores obtenidos pueden ser más bajos en las primeras 72 horas, nunca tanto como para no poder determinar con seguridad el sexo cromatínico en aquellos casos que nacen con genitales externos ambiguos(AU)