Atherothrombosis and Oxidative Stress: Mechanisms and Management in Elderly

Significance: The incidence of cardiovascular events (CVEs) increases with age, representing the main cause of death in an elderly population. Aging is associated with overproduction of reactive oxygen species (ROS), which may affect clotting and platelet activation, and impair endothelial function, thus predisposing elderly patients to thrombotic complications. Recent Advances: There is increasing evidence to suggest that aging is associated with an imbalance between oxidative stress and antioxidant status. Thus, upregulation of ROS-producing enzymes such as nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and myeloperoxidase, along with downregulation of antioxidant enzymes, such as superoxide dismutase and glutathione peroxidase, occurs during aging. This imbalance may predispose to thrombosis by enhancing platelet and clotting activation and eliciting endothelial dysfunction. Recently, gut-derived products, such as trimethylamine N-oxide (TMAO) and lipopolysaccharide, are emerging as novel atherosclerotic risk factors, and gut microbiota composition has been shown to change by aging, and may concur with the increased cardiovascular risk in the elderly. Critical Issues: Antioxidant treatment is ineffective in patients at risk or with cardiovascular disease. Further, anti-thrombotic treatment seems to work less in the elderly population. Future Directions: Interventional trials with antioxidants targeting enzymes implicated in aging-related atherothrombosis are warranted to explore whether modulation of redox status is effective in lowering CVEs in the elderly

A cholinergic-sympathetic pathway primes immunity in hypertension and mediates brain-to-spleen communication

The crucial role of the immune system in hypertension is now widely recognized. We previously reported that hypertensive challenges couple the nervous drive with immune system activation, but the physiological and molecular mechanisms of this connection are unknown. Here, we show that hypertensive challenges activate splenic sympathetic nerve discharge to prime immune response. More specifically, a vagus-splenic nerve drive, mediated by nicotinic cholinergic receptors, links the brain and spleen. The sympathetic discharge induced by hypertensive stimuli was absent in both coeliac vagotomized mice and in mice lacking α7nAChR, a receptor typically expressed by peripheral ganglionic neurons. This cholinergic-sympathetic pathway is necessary for T cell activation and egression on hypertensive challenges. In addition, we show that selectively thermoablating the splenic nerve prevents T cell egression and protects against hypertension. This novel experimental procedure for selective splenic denervation suggests new clinical strategies for resistant hypertension

Targeting interleukin-1β protects from aortic aneurysms induced by disrupted transforming growth factor β signaling

Aortic aneurysms are life-threatening conditions with effective treatments mainly limited to emergency surgery or trans-arterial endovascular stent grafts, thus calling for the identification of specific molecular targets. Genetic studies have highlighted controversial roles of transforming growth factor β (TGF-β) signaling in aneurysm development. Here, we report on aneurysms developing in adult mice after smooth muscle cell (SMC)-specific inactivation of Smad4, an intracellular transducer of TGF-β. The results revealed that Smad4 inhibition activated interleukin-1β (IL-1β) in SMCs. This danger signal later recruited innate immunity in the adventitia through chemokine (C-C motif) ligand 2 (CCL2) and modified the mechanical properties of the aortic wall, thus favoring vessel dilation. SMC-specific Smad4 deletion in Il1r1- or Ccr2-null mice resulted in milder aortic pathology. A chronic treatment with anti-IL-1β antibody effectively hampered aneurysm development. These findings identify a mechanistic target for controlling the progression of aneurysms with compromised TGF-β signaling, such as those driven by SMAD4 mutations

Investigation on the feasibility of integration of high temperature solar energy in a textile factory

Thermal energy production from fossil fuels is very common in many applications, especially in industrial processes. In a global context where great attention is being focused on reducing pollution and greenhouse gas production, the integration of renewable energy in industrial applications is very interesting. This is even more important considering that greenhouse gas emission for industrial processes is a great portion of their total emission. Considering the above, it appears that the integration of high temperature solar panels in industrial processes is quite an attractive prospect. The working temperatures of parabolic solar collectors are, for example, generally close to those of the thermal fluids used in many industrial processes, and parabolic solar collectors are a well known technology with several applications primarily used in electric production systems. Nonetheless, only a few examples of industrial integration have been studied or built. In this study, the integration of a concentrating solar thermal plant in a textile factory has been examined both from the thermodynamic and economic point of view. An existing textile factory was chosen as a case study and its annual consumption of thermal energy characterized. A model of the plant with solar energy integration was developed and simulated with TRNSYS over a one year time period. The plant was simulated considering the panel characteristics provided by the manufacturer and the local irradiation data. The influence of several plant parameters has been investigated in order to estimate their importance on performance and plant suitability

Experimental investigation on industrial drying process of cotton yarn bobbins: energy consumption and drying time

Abstract In the textile industry, the drying process is a time consuming and energy expensive operation that influences strongly the cost of the textile finishing operations. For this reason, the study of innovative techniques plays a key role to decrease the energy consumption, the costs and the environmental impact. After a first mechanical process, the moisture is removed from yarn fibers by a thermal convection dryer that delivers hot air through the material. In this study, the drying process of cotton yarn bobbins is experimentally analyzed. With this aim, an experimental test rig was developed based on the geometry of industrial dryers. The influence of the drying air path and the air working conditions was assessed by performing tests with different configurations, temperatures and pressures. The results were analyzed in terms of drying time and energy consumption as the optimum drying condition is a trade-off between these parameters

Uncertainty Quantification of the Effects of Blade Damage on the Actual Energy Production of Modern Wind Turbines

Wind turbine blade deterioration issues have come to the attention of researchers and manufacturers due to the relevant impact they can have on the actual annual energy production (AEP). Research has shown how after prolonged exposure to hail, rain, insects or other abrasive particles, the outer surface of wind turbine blades deteriorates. This leads to increased surface roughness and material loss. The trailing edge (TE) of the blade is also often damaged during assembly and transportation according to industry veterans. This study aims at investigating the loss of AEP and efficiency of modern multi-MW wind turbines due to such issues using uncertainty quantification. Such an approach is justified by the stochastic and widely different environmental conditions in which wind turbines are installed. These cause uncertainties regarding the blade's conditions. To this end, the test case selected for the study is the DTU 10 MW reference wind turbine (RWT), a modern reference turbine with a rated power of 10 MW. Blade damage is modelled through shape modification of the turbine's airfoils. This is done with a purposely developed numerical tool. Lift and drag coefficients for the damaged airfoils are calculated using computational fluid dynamics. The resulting lift and drag coefficients are used in an aero-servo-elastic model of the wind turbine using NREL's code OpenFAST. An arbitrary polynomial chaos expansion method is used to estimate the probability distributions of AEP and power output of the model when blade damage is present. Average AEP losses of around 1% are predicted mainly due to leading-edge blade damage. Results show that the proposed method is able to account for the uncertainties and to give more meaningful information with respect to the simulation of a single test case

Protective Effects of Borago officinalis (Borago) on Cold Restraint Stress-Induced Gastric Ulcers in Rats: A Pilot Study

Stress is a typical body's natural defense to a generic physical or psychic change. A specific linking mechanism between ulcer onset and psycho-physical stress prolonged exposure has been reported. We decided to investigate the possible effects of Borago officinalis L. (Borago) in preventing physical (stress)-induced gastric ulcers in a rat model. Eighty male Sprague-Dawley rats were randomly divided into 16 groups, pretreated with a control solution, omeprazole (20 mg/kg), Borago methanolic extract (25, 50, 100, 250, and 500 mg/kg), Borago organic extract (50, 100, 250, and 500 mg/kg), Borago aqueous extract (5, 10, 20, 30, and 40 mg/kg), and D(-)-2-Amino-5-phosphonovaleric acid (AP5) (25 mg/kg) and kept in stressful conditions such as water immersion and restraint-induced stress ulcers. The animals were sacrificed and their stomach scored for the severity and the number of gastric ulcers. Methanolic extract (500 mg/kg) significantly reduced both ulcer parameters (***p < 0.001 and **p < 0.01, respectively). Aqueous and organic extract significantly decreased severity score at 5 and 10 mg/kg (**p < 0.01 and ***p < 0.001, respectively), and at 250 and 500 mg/kg (***p < 0.001), respectively, while gastric ulcers' resulted number significantly reduced only at 10 mg/kg (*p < 0.05) and at 500 mg/kg (**p < 0.01), respectively. On the other hand, aqueous extract significantly increased the mucosal gastric content of cAMP (*p < 0.05) and NR2A and NR2B subunits (*p < 0.05 and **p < 0.01, respectively) at 5 mg/kg. Organic extract showed also a significant cytotoxic effect at 500 and 1,000 mg/kg with a 3T3 cell viability reduction of 43.6% (**p < 0.01) and 92.1% (***p < 0.001), respectively. Borago aqueous extract at 10 mg/kg could be considered as a potential protective agent against stress-induced ulcers, and it is reasonable to possibly ascribe such protective activity to a modulation of the NR2A and NR2B subunit expression

Extra virgin olive oil use is associated with improved post-prandial blood glucose and LDL cholesterol in healthy subjects

Extra virgin olive oil (EVOO) is a key component of the Mediterranean diet and seems to account for the protective effect against cardiovascular disease. However, the underlying mechanism is still elusive