Metalloproteases, vascular remodeling and atherothrombotic syndromes

Defects in the synthesis and breakdown of the extracellular matrix (ECM) are now seen as key processes in the development of atherosclerosis and its thrombotic complications. Correlations have been observed between circulating levels of ECM biomarkers and the clinical manifestations of and risk factors for atherosclerosis. Several matrix metalloproteinases (MMPs), endopeptidases that can degrade the ECM, such as MMP-9 and MMP-10, play important roles in the pathophysiology of atherothrombosis and contribute to the expansion of abdominal aortic aneurysms. Moreover, they may also be useful biomarkers of atherosclerotic risk and serve as predictors of coronary and cerebrovascular disease recurrence. Although at present the effect of tissue inhibitors of MMPs (TIMPs) on cardiovascular disease prognosis is still uncertain, the ECM could be a promising therapeutic target in atherothrombotic disease, and several MMP inhibitors are currently undergoing clinical trials

Experimental evaluation of cement mortars with recycled brass fibres from the electrical discharge machining process

This paper aims to evaluate the effect of recycled brass fibres on the physical, thermal and mechanical properties of cementitious mortars. For that purpose, seven different mortars, with the same water/cement ratio but using two different brass fibres were manufactured. Not-machined brass fibres were used as a reference and compared to the waste brass fibres obtained as a by-product of wire cutting methods through electrical discharge machines. Both fibres were added to the mortars in proportions of 0.25%, 0.5% and 1% by volume of mortar. The morphology and presence of elements in the fibres were evaluated by scanning electron microscopy (SEM) coupled with energy dispersive X-ray spectroscopy (EDX). In addition, ultrasonic pulse velocity and thermal conductivity were measured to evaluate the mortar quality and the fibre dispersion into the mortar specimens. Mechanical properties were studied through flexural and compression tests. Since the fibres present a reduced length, the effect on both porosity and bulk density is negligible and the reduction on ultrasonic pulse velocity and compression strength and the slight increment on flexural strength is not remarkable due to the limited anchorage provided. Nonetheless, the improvement in the thermal conductivity of the developed mortars with recycled brass fibres, supports focusing on the niche market of heating installations, such as underfloor heating or closed-loop geothermal heat exchangers.This work has been partly financed within the European Horizon 2020 Joint Technology Initiative Shift2Rail through contract no. 826255 (IN2TRACK2). This work has also been co-financed with the project Elkartek 2019 ref. KK-2019/00023 (GOLIAT2). The authors also wish to thank the Basque Government for financial assistance through IT919-16 and IT1314-19

Experimental evaluation of cement mortars with recycled brass fibres from the electrical discharge machining process

This paper aims to evaluate the effect of recycled brass fibres on the physical, thermal and mechanical properties of cementitious mortars. For that purpose, seven different mortars, with the same water/cement ratio but using two different brass fibres were manufactured. Not-machined brass fibres were used as a reference and compared to the waste brass fibres obtained as a by-product of wire cutting methods through electrical discharge machines. Both fibres were added to the mortars in proportions of 0.25%, 0.5% and 1% by volume of mortar. The morphology and presence of elements in the fibres were evaluated by scanning electron microscopy (SEM) coupled with energy dispersive X-ray spectroscopy (EDX). In addition, ultrasonic pulse velocity and thermal conductivity were measured to evaluate the mortar quality and the fibre dispersion into the mortar specimens. Mechanical properties were studied through flexural and compression tests. Since the fibres present a reduced length, the effect on both porosity and bulk density is negligible and the reduction on ultrasonic pulse velocity and compression strength and the slight increment on flexural strength is not remarkable due to the limited anchorage provided. Nonetheless, the improvement in the thermal conductivity of the developed mortars with recycled brass fibres, supports focusing on the niche market of heating installations, such as underfloor heating or closed-loop geothermal heat exchangers.This work has been partly financed within the European Horizon 2020 Joint Technology Initiative Shift2Rail through contract no. 826255 (IN2TRACK2). This work has also been co-financed with the project Elkartek 2019 ref. KK-2019/00023 (GOLIAT2). The authors also wish to thank the Basque Government for financial assistance through IT919-16 and IT1314-19

Thermal and Mechanical Properties of Mortars Reinforced with Recycled Brass Fibres

This paper aims to encourage the circular economy and merge the manufacturing and the construction industries, providing waste fibres from the electrical discharge machining of the former as raw material for the latter. The research analyses the effect on the physical, thermal and mechanical properties of mortars reinforced with brass fibres. The manuscript deals with different fibre length (10 mm, 15 mm and 25 mm) in variable percentages (0.5%, 1%, 2% and 4%). Larger amounts and longer fibres tend to increase the thermal conductivity whereas post cracking flexural strength is more dependent on fibre length.This work has been partly financed within the European Horizon 2020 Joint Technology Initiative Shift2Rail through contract no. 826255 (IN2TRACK2) . This work has also been cofinanced with the project Elkartek 2019 ref. KK-2019/00023 (GOLIAT2) . The authors also wish to thank the Basque Government for financial assistance through IT919-16 and IT131419

Structural and Electronic Properties of Graphene Oxide for Different Degree of Oxidation1

In the last year, the investigation of two-dimensional materials as graphene oxide is a fundamental goal to produce innovative devices with wide range of applications in many areas. In the present work, we report a systematic study of structural and electronic properties of graphene oxide for different oxidations levels (25%, 50%, 75%, 100%) using density functional calculations for electronic ground state and a statistical approach on carbon-carbon bond length obtained after the geometric optimization of graphene covered with epoxide and hydroxyl functional groups. The theoretical models proposed and studied here are accord with the well-known experimental data. Our statistical results of the carbon-carbon bond length shown that hydroxyl groups disturbs the structure of graphene more than epoxide groups, however, both hydroxyl and epoxide groups are responsible of the change of hybridization sp2 to sp3, while the degree of oxidation increase. In addition, our electronic structure calculations confirm that with low degree of oxidation, the graphene oxide is semiconductor, and with full degree of oxidation graphene oxide is an insulating material. The minimum of total energy is found when the graphene oxide has full coverage. This work can contribute to understand the plasticity and ductility properties of graphene oxide recently reported

proMetalloproteinase-10 is associated with brain damage and clinical outcome in acute ischemic stroke

BACKGROUND: Matrix metalloproteinases (MMPs) mediate tissue injury during stroke but also neurovascular remodeling and we have shown that MMP-10 is involved in atherothrombosis. OBJECTIVE: The purpose of this study was to examine the relationship between proMMP-10 and clinical outcome, assessing inflammatory and proteolytic markers, in patients with acute ischemic stroke. METHODS: We prospectively studied 76 patients with ischemic stroke treated with tPA within the first 3 h from symptom onset, compared with 202 non-tPA-treated ischemic stroke patients and 83 asymptomatic subjects. Stroke severity was assessed with the National Institutes of Health Stroke Scale (NIHSS). Hemorrhagic transformation (HT) and severe brain edema were diagnosed by cranial CT. Good functional outcome was defined as a modified Rankin scale score </= 2 at 90 days. Serum levels of MMP-9, proMMP-10, TIMP-1, tumor necrosis factor-alpha (TNFalpha), interleukin-6 and cellular fibronectin were measured at admission. The effect of TNFalpha on endothelial proMMP-10 was assessed in vitro. RESULTS: Serum proMMP-10 concentration in ischemic stroke patients, non-treated or treated with t-PA, which was higher than age-matched healthy subjects (P < 0.0001), was independently associated with higher infarct volume, severe brain edema, neurological deterioration and poor functional outcome at 3 months (all P < 0.05), but not with HT. proMMP-10 levels were also independently and positively associated with circulating levels of TNFalpha (P < 0.0001), which induced its endothelial expression in vitro, both mRNA and protein. MMP-9, however, was only associated with HT and severe edema (all P < 0.05). CONCLUSIONS: Increased serum proMMP-10 after acute ischemic stroke, associated with TNFalpha, is a new marker of brain damage and poor outcome

Análisis plástico y Ensayos de Losas multidireccionales de HRFA

This paper presents a theoretical and experimental study of multidirectional steel fibers reinforced concrete slabs (SFRC). The study is based on a real building application using SFRC flag slabs. For the evaluation of the slabs bearing capacity, plastic calculations are performed both at section and structure levels. The section analysis uses the perfect plastic stress-strain diagram, with reference to the values of the strength characteristics of SFRC based on previous jobs that used similar fibers and dosages. In the structure analysis the plastic yield lines method has been used. This method relates the section last bearing moment and the plastic collapse load. The experimental campaign has consisted of the testing of six 2 m. diameter circular shaped slabs prototypes, and has allowed to verify the reference resistance used in the calculations.En este trabajo se realiza un estudio teórico- experimental de losas multidireccionales de hormigón reforzado con fibras de acero (HRFA). El estudio se enmarca en una aplicación de un edificio real usando HRFA en los forjados. Para la evaluación de la capacidad resistente de las losas, se realizan cálculos plásticos, tanto a nivel de sección como de estructura. A nivel de sección se emplea el diagrama tensión-deformación plástico perfecto, tomando como referencia los valores de las características resistentes del HRFA aportados en trabajos anteriores que emplearon fibras y dosificaciones similares. A nivel de estructura se emplea el método plástico de las líneas de rotura, que relaciona el momento último de la sección la carga de colapso plástico. La campaña experimental, consiste en ensayar seis prototipos en forma de loseta circular de 2 m de diámetro, verificando el valor de la resistencia de referencia empleada en los cálculos

Evidence that heparin but not hirudin reduces PAI-1 expression in cultured human endothelial cells

Heparin and other antithrombotic drugs besides their anticoagulant action could have a profibrinolytic effect. We have analyzed the effect of unfractionated heparin (UFH) and hirudin on PAI-1 gene expression in human umbilical vein endothelial cells (HUVEC). Cells were stimulated with UFH (1 and 10 IU/ml) and hirudin (20 and 100 TIU/ml). Samples were obtained before and 2, 6, and 24 hours after stimulation. mRNA analysis was conducted by reverse transcription followed by polymerase chain reaction, and PAI-1 antigen was determined by ELISA. Addition of UFH (10 IU/ml) to HUVEC resulted in a decrease of PAI-1 mRNA at 6 hours (40% reduction) and 24 hours (60% reduction) and PAI-1 antigen. Hirudin, however, did not modify significantly the PAI-1 mRNA nor the inhibitor secretion. The addition of UFH (10 or 100 IU/ml) to endotoxin-stimulated HUVEC also reduced the increased PAI-1 mRNA and antigen secretion (45%), whereas no effect could be observed with hirudin. Our results suggest that UFH, but not hirudin, by reducing the endothelial expression of PAI-1 might have a profibrinolytic effect

The 4G/5G PAI-1 polymorphism influences the endothelial response to IL-1 and the modulatory effect of pravastatin

BACKGROUND: Increased plasminogen activator inhibitor (PAI-1) levels lead to impaired fibrinolytic function associated with higher cardiovascular risk. PAI-1 expression may be regulated by different inflammatory cytokines such as interleukin-1alpha (IL-1). Several polymorphisms have been described in the PAI-1 gene. AIM: We examined the influence of the 4G/5G polymorphism in the promoter region on IL-1alpha-induced PAI-1 expression by human umbilical vein endothelial cells (HUVEC) in presence or absence of pravastatin. METHODS AND RESULTS: Genotyped HUVEC were incubated with IL-1alpha (500 U mL(-1)) in presence or absence of pravastatin (1-10 microm). PAI-1 expression was analyzed by real time polymerase chain reaction (PCR), and PAI-1 antigen measured in supernatants by ELISA. IL-1alpha increased PAI-1 secretion in a genotype-dependent manner, and higher values were observed for 4G/4G compared with both 4G/5G and 5G/5G cultures (P < 0.05). Preincubation of HUVEC with 10 microm pravastatin significantly reduced IL-1-induced PAI-1 expression in 4G/4G HUVEC compared with untreated cultures (177.5% +/- 24.5% vs. 257.9% +/- 39.0%, P < 0.05). Pravastatin also attenuated the amount of secreted PAI-1 by 4G/4G HUVEC after IL-1 stimulation (5020.6 +/- 165.7 ng mL(-1) vs. 4261.1 +/- 309.8 ng mL(-1), P < 0.05). This effect was prevented by coincubation with mevalonate, indicating a dependence on HMG-CoA reductase inhibition. CONCLUSIONS: The endothelial 4G/5G PAI-1 genotype influences the PAI-1 response to IL-1alpha and the modulatory effect of pravastatin. As increased PAI-1 levels have been linked to cardiovascular disease the observed endothelial modulation by pravastatin may have potential clinical implications