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This research was funded by Ministerio de Economia y Competitividad, grant number BFU-2016-80316-R., Exogenous neuroprotective protein neuroglobin (Ngb) cannot cross the blood–brain barrier. To overcome this difficulty, we synthesized hyaluronate nanoparticles (NPs), able to deliver Ngb into the brain in an animal model of stroke (MCAO). These NPs effectively reached neurons, and were microscopically identified after 24 h of reperfusion. Compared to MCAO non-treated animals, those treated with Ngb-NPs showed survival rates up to 50% higher, and better neurological scores. Tissue damage improved with the treatment, but no changes in the infarct volume or in the oxidative/ nitrosative values were detected. A proteomics approach (p-value < 0.02; fold change = 0.05) in the infarcted areas showed a total of 219 proteins that significantly changed their expression after stroke and treatment with Ngb-NPs. Of special interest, are proteins such as FBXO7 and NTRK2, which were downexpressed in stroke, but overexpressed after treatment with Ngb-NPs; and ATX2L, which was overexpressed only under the effect of Ngb. Interestingly, the proteins affected by the treatment with Ngb were involved in mitochondrial function and cell death, endocytosis, protein metabolism, cytoskeletal remodeling, or synaptic function, and in regenerative processes, such as dendritogenesis, neuritogenesis, or sinaptogenesis. Consequently, our pharmaceutical preparation may open new therapeutic scopes for stroke and possibly for other neurodegenerative pathologies., Spanish Government BFU-2016-80316-R

Some biological drugs with proven neuroprotective capacity are unable to cross the blood brain barrier (BBB), preventing its use in neuroregenerative diseases such as stroke. The use of nanoparticles as a delivery system to transport large therapeutic molecules to the cerebral parenchyma may be a good option to overcome this limitation. To achieve this goal, we have designed some polymer nanoparticles (NPs) by two ionic gelation methods of synthesis: external (M1) and internal (M2), both using sodium hyaluronate (SH) as polymer but with differences in the elaboration of their core. Additionally, both SH-NPs were coated with chitosan and glycerol tripalmitin in order to improve their penetration capabilities into cells. The nanoparticles were characterized by size, shape and charge. Then, an experimental approach was carried out in animals submitted to a stroke model, where NPs penetration into the brain was studied and analysed after its systemic administration. All types of NPs assayed were able to cross the BBB and were endocytosed by neurons; however, the SH-NPs obtained by M2 are lightly more efficient in the rate of penetration than those obtained by M1. There were not visible differences between coated and non-coated NPs obtained by both gelation methods. This may be due to the fact that not only the size, shape and charge of NPs, but also its chemical structure influences its cellular capture by endocytic mechanisms.

Diseases and disorders of the nervous system, like Parkinson disease (PD) and other neurodegenerative pathologies, are widespread in our society. The arsenal of treatments against these pathologies continues to increase, but in many cases, its use is limited. This is due to the blood-brain barrier (BBB), which acts by limiting the penetration of drugs into the brain. To overcome this handicap, in the current research, solid lipid nanoparticles (SLNPs) able to encapsulate drugs and to cross the blood-brain barrier have been designed to transport and release these drugs into their targets. These SLNPs were synthesized by a sonication method and high agitation process searching the most adequate physicochemical profile to achieve the objectives set. Today, the most efficient treatment for PD consists of providing the dopamine (DP) that is lost by neurodegeneration; however, the nature of this neurotransmitter prevents its crossing of the BBB. Therefore, DP may be considered as a good candidate to be encapsulated in SLNPs while studying how the loading drug could affect such nanoparticles. Based on these antecedents, in this research, both empty and DP-charged SLNPs were characterized physicochemically. The results obtained indicated a great stability of the nanoparticles loaded with DP when drug was used at 0.2 to 0.05%; these concentrations barely affected its size, polydispersity, and ζ-potential, and the SLNPs elaborated in this research were high appropriate to be injected systemically. Finally, empty SLNPs labeled and administered systemically to adult male Wistar rats demonstrate their penetration ability into the brain parenchyma.

Amorphization serves as a strategy for the improvement of poor dissolution characteristics of many drug compounds. However, in many formulations the content of polymeric stabilizer is high, which is undesirable from the perspective of future applications. Thus, studying the compositiondependent stability of amorphous solid dispersions seems to be demanded. In this paper, we describe the amorphization of ezetimibe, a lipid-lowering drug, in the spray drying process and investigate the effect of polyvinylpyrrolidone-co-poly(vinyl acetate) (PVP/VA) content on the physical stability and dissolution characteristics of the drug. Fully amorphous systems were obtained when the concentration of the polymer in solid dispersion was as low as 20%. The amorphization led to the dissolution enhancement by even 70%, with a noticeable sudden increase at around 40% of PVP/VA content and very small variations for systems having 66–90% PVP/VA. It was also correlated to wettability characteristics of solid dispersions, which may suggest that in the vicinity of 40% of the polymer content, the behavior of the system becomes independent of the PVP/VA content., Polish National Science Centre, grant number 2015/16/W/NZ7/00404

Nonsteroidal anti-inflammatory drugs (NSAIDs) constitute a heterogeneous group of compounds that exhibit analgesic, anti-inflammatory and antipyretic activity. However, the GI damage produced by NSAIDs has been widely studied. Thus, the aim of the present study was the development of mesoporous silica nanoparticles in order to increase the capacity of drug transport, emphasizing those with low solubility such as NSAIDs. The morphology and structure characteristics of the synthesized nanoparticles were studied by transmission electron microscopy (TEM), besides, its particle size, surface charge, specific area and cell viability will be determined. The analytical application of mesoporous silica nanoparticles as ibuprofen carrier was also evaluated by measuring their drug loading characteristics and release behavior. The results showed that the synthesized NPs had efficient physicochemical characteristics, high EE%, low toxicity, and controlled ibuprofen release., CTS-205

Diseases and disorders of the nervous system, like Parkinson disease (PD) and others neurodegenerative pathologies are widespread in our society. The arsenal of treatments against these pathologies continues to increase, but in many cases its use is limited. This is due to the blood-brain barrier (BBB), which acts by limiting the penetration of drugs into the brain. To overcome this handicap, in the current research solid lipid nanoparticles (SLNPs) able to encapsulate drugs and to cross the blood-brain barrier have been designed to transport and release these drugs into their targets. These SLNPs were synthesized by a sonication method and high agitation process searching the most adequate physicochemical profile to achieve the objectives set. Today, the most efficient treatment for PD consists of providing the dopamine (DP) that is lost by neurodegeneration; however, the nature of this neurotransmitter prevents its crossing of the BBB. Therefore, DP may be considered as a good candidate to be encapsulated in SLNPs while studying how the loading drug could affect such nanoparticles. Based on these antecedents, in this research, both empty and DP-charged SLNPs were characterized physicochemically. The results obtained indicated a great stability of the nanoparticles loaded with DP when drug was used at 0.2 to 0.05%; these concentrations barely affected its size, polydispersity and ζ-potential, and the SLNPs elaborated in this research were high appropriate to be injected systemically. Finally, empty SLNPs labeled and administered systemically to adult male Wistar rats demonstrate their penetration ability into the brain parenchyma.

The formation of solid dispersions with the amorphous drug dispersed in the polymeric matrix improves the dissolution characteristics of poorly soluble drugs. Although they provide an improved absorption after oral administration, the recrystallization, which can occur upon absorption of moisture or during solidification and other formulation stages, serves as a major challenge. This work aims at understanding the amorphization-recrystallization changes of bicalutamide. Amorphous solid dispersions with poly(vinylpyrrolidone-co-vinyl acetate) (PVP/VA) were obtained by either ball milling or spray drying. The applied processes led to drug amorphization as confirmed using X-ray diffraction and differential scanning calorimetry. Due to a high propensity towards mechanical activation, the changes of the crystal structure of physical blends of active pharmaceutical ingredient (API) and polymer upon pressure were also examined. The compression led to drug amorphization or transition from form I to form II polymorph, depending on the composition and applied force. The formation of hydrogen bonds confirmed using infrared spectroscopy and high miscibility of drug and polymer determined using non-isothermal dielectric measurements contributed to the high stability of amorphous solid dispersions. They exhibited improved wettability and dissolution enhanced by 2.5- to 11-fold in comparison with the crystalline drug. The drug remained amorphous upon compression when the content of PVP/VA in solid dispersions exceeded 20% or 33%, in the case of spray-dried and milled systems, respectively., Polish National Science Centre 2015/16/W/NZ7/00404

Therapies against stroke can restore the blood supply but cannot prevent the ischemic damage nor stimulate the recovery of the infarcted zone. The neuroglobin protein plays an important role in the neuro-regeneration process after stroke, however, the method for its effective systemic application has not been identified yet, as neuroglobin is unable to pass through the blood-brain barrier. Previously, we developed different types of sodium hyaluronate nanoparticles, which successfully cross the blood-brain barrier after stroke. In this work, these nanoparticles have been used to carry neuroglobin through the bloodstream to the nerve cells in rats submitted to stroke. We have biosynthesized rat-recombinant neuroglobin and determined the formulation of sodium hyaluronate nanoparticles loaded with neuroglobin, as well as its size and &zeta, potential, encapsulation efficiently, in vitro release, and its kinetic of liberation. The results show that the formulation achieved is highly compatible with pharmaceutical use and may act as a delivery system to transport neuroglobin within the blood. We have found that this formulation injected intravenously immediately after stroke reached the damaged cerebral parenchyma at early stages (2 h). Neuroglobin colocalizes with its nanocarriers inside the nerve cells and remains after 24 h of reperfusion. In conclusion, the systemic administration of neuroglobin linked to nanoparticles is a potential neuroprotective drug-delivery strategy after stroke episodes.

Until recently mental diseases were treated as a whole, without any differentiation. Recent researchs have highlighted the differences between some of them, so consequently there are specific treatments for these pathologies today. The main objective of this work is to show two different diseases which in many cases are confused: depression and schizophrenia. These pathologies can have as triggers situations very diverse and that require different treatment. For the analysis, we are going to use two films: Prozac Nation (2001) by Erik Skjoldbjaerg and A beautiful mind (2001) by Ron Howard, which reflect the real experiences of two characters; the society in which they live and the environment around them, but especially focusing in the pharmacotherapy area, medications used, its correct use, the adverse effects and so on; in order to be able to decide if the vision presented by films has a formative character in these diseases. Hasta hace poco tiempo las enfermedades mentales eran tratadas como un todo, sin diferenciación alguna; las investigaciones realizadas en estos últimos años han resaltado las diferencias existentes entre algunas de ellas, de tal forma que hoy en día existen tratamientos específicos para las patologías descritas. El objetivo principal de este trabajo, es el de mostrar dos enfermedades diferentes pero que en muchos casos se confunden, depresión y esquizofrenia. Patologías que pueden tener como desencadenantes, situaciones muy diversas y que requieren un tratamiento farmacológico diferente. Para ello, se realizará un análisis de dos películas, Prozac Nation (2001) de Erik Skjoldbjaerg y Una mente maravillosa (2001) de Ron Howard que reflejan las vivencias reales de dos personajes; se analizará la sociedad en la que conviven y el entorno que les rodea, pero resaltando muy especialmente el apartado de la farmacoterapia, que medicamentos se utilizan, si es correcto su uso, los efectos adversos que presentan… para de esta forma poder prever si la visión de la película tiene carácter formativo en este tipo de temática.

Objetivos: La bibliometría es un tipo de estudio estadístico sobre datos científicos. Mediante esta herramienta queremos valernos para visualizar distintos aspectos que presentan los medicamentos biosimilares, su importancia y el impacto que generan en su entorno. Métodos: se ha utilizando como motor de búsqueda Science Direct, así como de publicaciones científicas referenciadas en la bibliografía y como de algunas webs sobre la materia. Resultados: Casi todos los indicadores señalan la gran importancia económica que concierne entorno a los medicamentos biosimilares, la actualidad que presenta y que gran parte de su estudio se concentra alrededor de los pacientes. Conclusiones: Con este trabajo se comprueba el gran interés que ofrecen los biosimilares y sobre todo el impacto que tendrán en un futuro, así como las repercusiones que traerán consigo, sobre todo en los campos económicos y de la salud., Objectives: A bibliometrics study is a type of statistical study on scientific data. With this tool we want to visualize different aspects of biosimilar drugs, their importance and the impact they generate in their environment. Methods: Science Direct was utilized as a search engine, in addition to the scientific publications referenced in the bibliography as well as some websites concerning the subject. Results: Almost all the indicators point to the great economic importance of biosimilar drugs, their novelty and their patient-coentered focus. Conclusions: It is of great interest to know the future impact that these medicines will have and the repercussions they will bring, especially in the economic and health fields., Grupo de Farmacia practica (CTS-205 Junta de Andalucía) proyecto investigación BFU2016-80316-R. Ministerio de Economía y Competitividad.

Background Embolic stroke is a major concern in atrial fibrillation (AF), and anticoagulation is the therapy of choice to prevent it. Around 20% of patients with AF have contraindications for anticoagulation (OAC). The left atrial appendage (LAA) has been identified as the most common place of thrombosis in patients with AF, particularly in those with non-valvular AF or impaired ventricular function. LAA occlusion reduces the incidence of embolic events in these patients. This article describes a case of percutaneous closure of LAA with the Amplatzer Cardiac Plug device. The patient was at high risk of embolism and had absolute contraindication for OAC. The procedure was performed at the cardiac catheterization laboratory under general anesthesia with fluoroscopic guidance and transesophageal echocardiography, and complete closure of the LAA was achieved. During the procedure, no complications were reported. The patient remained event-free at three-month follow-up, with complete exclusion of LAA. No embolic events have been reported.

Resumen es: Introduccion El tratamiento antiagregante dual con aspirina y clopidogrel constituye un tratamiento esencial para la prevencion de eventos isquemicos en ...

Background Conventional coronary angiography (CA) is the gold standard for the diagnosis of coronary artery disease. However, this technique requires several orthogonal projections to determine the severity of the disease. Dual-axis rotational coronary angiography (DARCA) is a new technique which acquires the image of each coronary artery using a single contrast injection, potentially reducing both radiation and contrast exposure. Objective The aim of this study was to determine the amount of contrast used, radiation exposure and diagnostic accuracy of DARCA compared to conventional CA. Methods We conducted a prospective, self-controlled study of consecutive patients undergoing elective coronary angiography to compare DARCA versus the conventional technique. All the angiographies were reviewed by two independent interventional cardiologists (observer 1 and observer 2) who evaluated agreement between both types of images. The observers evaluated firstly DARCA and three weeks later conventional CA images to prevent bias in their interpretation. Results The contrast volume used in the diagnostic procedure was significantly lower with DARCA (33.29 ± 11.2 ml vs. 17±5.4 ml; p < 0.01). Radiation exposure in the patient (235.6 ± 76.8 mGy vs. 82.7 ± 46.6 mGy; p