Useful Role of a New Generation of Dexamethasone, Vitamin E and Human Serum Albumin Microparticles in the Prevention of Excitotoxicity Injury in Retinal Ocular Diseases.

Excitotoxicity has been linked to the pathogenesis of several serious degenerative ocular diseases. Long-term overactivation of the NMDA receptor by glutamate in retinal ganglion cells (RGCs) results in degeneration, apoptosis and loss of function leading to blindness. NMDA receptor antagonists have been proposed as a pharmacological blockage of glutamate excitotoxicity. However, an inhibition of the pathway activated by glutamate receptors has intolerable side effects. An interesting pharmacological alternative would be the use of antiapoptotic compounds as RGCs' neuroprotective active substances. Several mechanisms have been proposed to explain neuroprotection, including anti-inflammatory and scavenging activities. Here, the role of dexamethasone in neuroprotection was studied. For this purpose, original controlled release systems composed of microparticles containing dexamethasone with or without vitamin E and human serum albumin (HSA) were designed. The particles were prepared by the solid-in-oil-in-water (S/O/W) emulsion-evaporation technique. After properly characterization of the particles, they were intravitreally injected into an rat model of acute ocular excitotoxicity injury. The functionality of the retina was determined by electroretinography and RGCs were counted after cell immunohistochemistry. These microparticulate systems showed the ability to maintain normal electroretinal activity and promoted significant protection of RGCs. Through this proof of concept, we demonstrated that dexamethasone could be a useful anti-inflammatory agent to avoid the progression of degenerative ocular diseases. Furthermore, when administered in controlled release systems that provide low concentrations during prolonged periods of time, not only can the patient's comfort be increased but the cytotoxicity of the drugs can also be avoided.

Ventricular Tachycardia as a Presentation of Isolated Cardiac Sarcoidosis: How to Manage It When We Do Not See Granulomas.

A 47-year-old male was referred for rapid palpitations and an electrocardiogram compatible with sustained monomorphic ventricular tachycardia (VT) that required synchronized electrical cardioversion due to hemodynamic instability. After the initial clinical certainty, an etiological search is carried out. The transthoracic echocardiogram (TTE) revealed moderate dilatation and left ventricular systolic dysfunction due to global hypokinesia. Coronary angiography did not show significant coronary stenosis. Cardiac magnetic resonance (CMR) guarantees a nonischemic dilated cardiomyopathy with moderate systolic dysfunction and a pattern of subepicardial and intramyocardial late gadolinium enhancement (LGE) in medial-lateral and median inferolateral segments. Lastly, a positron emission tomography-computed tomography (PET-CT) scan showed diffuse fixation of the radiotracer in the left ventricular (LV) walls, with greater uptake on the lateral and inferolateral surfaces of inflammatory origin. After ruling out other alternative pathologies and according to current diagnostic criteria, the clinical judgment of probable isolated cardiac sarcoidosis (ICS) is established. An implantable cardioverter-defibrillator was implanted as secondary prevention of the acute arrhythmic event. Specific treatment for systolic dysfunction was prescribed, as well as immunosuppressive therapy with corticosteroids and methotrexate, after which the patient remained in clinical remission, with disappearance of active inflammation on cardiac imaging tests and progressive ventricular systolic function. The initial diagnosis of isolated cardiac sarcoidosis can be complex and challenging, especially in those patients in whom the diagnosis of extracardiac sarcoidosis has not been previously established. The limitations of endomyocardial biopsy in this entity make it necessary to have a high index of clinical suspicion with the early use of new cardiac imaging techniques and to include this picture in the differential diagnosis of patients with sustained ventricular arrhythmias or left ventricular systolic dysfunction of nonspecific etiology clarified. Early initiation of aggressive immunosuppressive therapy has been shown to prevent disease progression and limit its potential cardiac complications.

Caracterización del impacto del evento en profesionales de la salud / Characterization of the impact of the event on health professionals / Caracterizando o impacto do evento sobre os profissionais de saúde

La pandemia por COVID-19 generó diversas consecuencias que afectaron la salud física y emocional de la población, siendo los profesionales de la salud los más afectados porque tuvieron la misión de afrontar la atención de todos los que padecieron la enfermedad, además tuvieron que enfrentar la escasez de equipos de protección y de personal. Objetivo. El objetivo de la investigación fue caracterizar el impacto de la pandemia por COVID-19 en los profesionales de la salud que trabajan en hospitales y centros de atención de Lima y provincias. Materiales y método. Investigación cuantitativa, descriptiva, no experimental y transversal. La recolección de los datos se realizó mediante la escala Impacto del estresor (EIE-R) versión española. La población de estudio fue de 624, luego se extrajo una muestra de 394 profesionales sanitarios, recogidos bajo muestreo no probabilístico. Resultados. Se halló que el 47,5% de los profesionales manifestó un impacto leve; el 52, 6% reporto impacto que va de moderado a severo, además se identificó que el contagio por COVID-19 fue el factor significativamente asociado al impacto del evento (p-valor 0.025). Conclusiones. Se identificó que la pandemia por COVID-19 ha generado un impacto en la salud de los profesionales que estuvieron al frente de la atención; se observó una prevalencia del impacto mayor en las trabajadoras que en el personal masculino.

The COVID-19 pandemic generated several consequences that affected the physical and emotional health of the population, being the health professionals the most affected because they had the mission to deal with the care of all those who suffered from the disease, in addition they had to face the shortage of protective equipment and personnel. Objective. The objective of the research was to characterize the impact of the COVID-19 pandemic on health professionals working in hospitals and health care centers in Lima and the provinces. Materials and Method. Quantitative, descriptive, non-experimental, cross-sectional research. Data were collected using the Spanish version of the Stressor Impact Scale (EIE-R). The study population was 624, then a sample of 394 health professionals was drawn, collected under non-probabilistic sampling. Results. It was found that 47.5% of the professionals reported a mild impact; 52.6% reported an impact ranging from moderate to severe, and it was also identified that infection by COVID-19 was the factor significantly associated with the impact of the event (p-value 0.025). Conclusions. It was identified that the COVID-19 pandemic has generated an impact on the health of the professionals who were in charge of the care; a higher prevalence of the impact was observed in female workers than in male personnel.

A pandemia COVID-19 gerou diversas conseqüências que afetaram a saúde física e emocional da população, sendo os profissionais de saúde os mais afetados porque tinham a missão de lidar com o cuidado de todos aqueles que sofriam da doença, além de ter que enfrentar a escassez de equipamentos e pessoal de proteção. Objetivo. O objetivo da pesquisa era caracterizar o impacto da pandemia COVID-19 sobre os profissionais de saúde que trabalham em hospitais e centros de atendimento em Lima e nas províncias. Materiais e método. Pesquisa quantitativa, descritiva, não-experimental, de corte transversal. A coleta de dados foi realizada utilizando a versão espanhola da Escala de Impacto Stressor (EIE-R). A população do estudo era de 624 pessoas, depois foi retirada uma amostra de 394 profissionais de saúde, coletada sob amostragem não-probabilística. Resultados. Foi constatado que 47,5% dos profissionais relataram um impacto leve; 52,6% relataram impacto moderado a severo, e a infecção por COVID-19 foi identificada como o fator significativamente associado ao impacto do evento (p-valor 0,025). Conclusões. Foi identificado que a pandemia da COVID-19 teve um impacto sobre a saúde dos profissionais que estavam encarregados dos cuidados; uma prevalência maior do impacto foi observada nas trabalhadoras do que no pessoal masculino.

Retinal Cell Protection in Ocular Excitotoxicity Diseases. Possible Alternatives Offered by Microparticulate Drug Delivery Systems and Future Prospects.

Excitotoxicity seems to play a critical role in ocular neurodegeneration. Excess-glutamate-mediated retinal ganglion cells death is the principal cause of cell loss. Uncontrolled glutamate in the synapsis has significant implications in the pathogenesis of neurodegenerative disorders. The exploitation of various approaches of controlled release systems enhances the pharmacokinetic and pharmacodynamic activity of drugs. In particular, microparticles are secure, can maintain therapeutic drug concentrations in the eye for prolonged periods, and make intimate contact by improving drug bioavailability. According to the promising results reported, possible new investigations will focus intense attention on microparticulate formulations and can be expected to open the field to new alternatives for doctors, as currently required by patients.

Interferencia analítica en la determinación de troponina por anticuerpos heterófilos / Interference in the determination of Troponin due to heterophile antibodies

Resumen Por su elevada especificidad y sensibilidad, y a raíz de la tercera definición universal de infarto estas isoformas cardiacas han sido aceptadas en el ámbito internacional como los biomarcadaores de elección en la práctica clínica para el diagnóstico de síndrome coronario agudo, preferibles a la determinación de las enzimas creatina quinasa y su isoforma MB. Se presenta el caso de un varón de ochenta años, quien, de manera persistente, tuvo valores elevados de troponinas, pese a evolución clínica no compatible con síndrome coronario agudo ni otras causas de elevación de este biomarcador.

Abstract Due to its elevated specificity and sensitivity, and on being the third universal definition of myocardial infarction, these cardiac isoforms have been accepted internationally as the biomarkers of choice in clinical practice for the diagnosis of acute coronary syndrome, and are preferable to the determinations of creatine kinase and its MB isoform. A case is presented on an eighty year-old man, who persistently had elevated Troponin values, despite a clinical course that was incompatible with an acute coronary syndrome or any other causes of elevation of this biomarker.

A Reassessment of the Marrubium Vulgare L. Herb's Potential Role in Diabetes Mellitus Type 2: First Results Guide the Investigation toward New Horizons.

Despite the wide variety of pharmacological activities described for the Marrubium vulgare L. herb, amazingly, only one clinical trial can be found in scientific literature. It was designed for the evaluation of its antidiabetic activity. Worse, the outcomes of this trial were contradictory to what previous in vivo mice assays had concluded. Therefore, should Marrubium vulgare be ruled out due to its lack of therapeutic potential in diabetes? The authors suggest a reevaluation of the clinical trial methodology to establish valid and final results.

Solving the puzzle: What is behind our forefathers' anti-inflammatory remedies?

Inflammation is a ubiquitous host response in charge of restoring normal tissue structure and function but is a double-edged sword, as the uncontrolled or excessive process can lead to the injury of host cells, chronic inflammation, chronic diseases, and also neoplastic transformation. Throughout history, a wide range of species has been claimed to have anti-inflammatory effects worldwide. Among them, Angelica sinensis, Tropaeolum majus, Castilleja tenuiflora, Biophytum umbraculum, to name just a few, have attracted the scientific and general public attention in the last years. Efforts have been made to assess their relevance through a scientific method. However, inflammation is a complex interdependent process, and phytomedicines are complex mixtures of compounds with multiple mechanisms of biological actions, which restricts systematic explanation. For this purpose, the omics techniques could prove extremely useful. They provide tools for interpreting and integrating results from both the classical medical tradition and modern science. As a result, the concept of network pharmacology applied to phytomedicines emerged. All of this is a step toward personalized therapy.

Experimental and Clinical Pharmacology of Ziziphus jujuba Mills.

Ziziphus jujuba Mills, 'annab' in Iran, 'ber' in India or 'pomme sourette' in France, is a species whose fruit (known warmly as 'the fruits of life' in China) has been consumed for centuries for its nutritional value. The food industry used it as a food additive and flavoring. The dry seeds, the crude leaves and the stem bark are still used in ethnopharmacology to treat digestive disorders and gastric ulcers as antitussive, laxative and hypotensive drugs; even now, it is used in China to treat children who suffer from typhoid fever, furuncle and ecthyma. In Taiwan, the dry seeds for the variety spinosa (Suan Zao Ren) are the second most commonly prescribed and used phytomedicine for insomnia. Its popularity and production have increased worldwide in recent years, especially in Europe. The European Pharmacopoeia Commission has been unable to elaborate upon the EP monograph on Ziziphi spinosae semen as was planned. The EMA has not made its recommendations yet. Is it still a gap in the scientific knowledge? Or is difficult for traditional Chinese medicinal herbs to fulfill the style and quality parameters that are required? Copyright © 2017 John Wiley & Sons, Ltd.

Pharmaceutical technology can turn a traditional drug, dexamethasone into a first-line ocular medicine. A global perspective and future trends.

Dexamethasone is one of the most prescribed glucocorticoids. It is effective and safe in the treatment of a wide variety of ocular conditions, including anterior and posterior segment inflammation. However, its half-life in the vitreous humor is very short, which means that it typically requires frequent administrations, thus reducing patient adherence and causing therapeutic failure. Innovative dexamethasone delivery systems have been designed in an attempt to achieve sustained release and targeting. The FDA has approved dexamethasone implants for the treatment of macular edema secondary to retinal vein occlusion and posterior segment noninfectious uveitis. Lenses, micro- and nanoparticles, liposomes, micelles and dendrimers are also proving to be adequate systems for maintaining optimal dexamethasone levels in the site of action. Pharmaceutical technology is turning a classical drug, dexamethasone, into a fashionable medicine.

Vehicle Maneuver Detection with Accelerometer-Based Classification.

In the mobile computing era, smartphones have become instrumental tools to develop innovative mobile context-aware systems. In that sense, their usage in the vehicular domain eases the development of novel and personal transportation solutions. In this frame, the present work introduces an innovative mechanism to perceive the current kinematic state of a vehicle on the basis of the accelerometer data from a smartphone mounted in the vehicle. Unlike previous proposals, the introduced architecture targets the computational limitations of such devices to carry out the detection process following an incremental approach. For its realization, we have evaluated different classification algorithms to act as agents within the architecture. Finally, our approach has been tested with a real-world dataset collected by means of the ad hoc mobile application developed.

Dendrimers as a promising tool in ocular therapeutics: Latest advances and perspectives.

Dendrimers have called the attention of scientists in the area of drug and gene delivery over the last two decades for their versatility, complexity and multibranching properties. Some strategies for optimizing drug pharmacokinetics and site-specific targeting using dendrimers have been proposed. Among them, those related to treating and managing ocular diseases are of special interest. Ocular therapies suffer from significant disadvantages, including frequent administration, poor penetration and/or rapid elimination. This review provides an overview of the recent and promising progress in the dendrimers field, focusing on both the anterior and posterior segments of the eye ocular targets, the use of dendrimers as a strategy for overcoming obstacles to the traditional treatment of ocular diseases and an outlook on future directions. Finally, a first approach to ocular safety with dendrimers is intended that accounts for the state-of-the-art science to date.

An Insight into a Blockbuster Phytomedicine; Marrubium vulgare L. Herb. More of a Myth than a Reality?

Aerial parts and the root of Marrubium vulgare L. (white horehound) have been traditionally used in Europe and in southern and eastern Mediterranean countries. During colonization, the plant was introduced in America to great levels of popularity because of the simplicity of its growing; it was especially popular in Mexico and Brazil, where it has been known as 'maromba', 'marroio' or 'marroio-branco'. Ethnopharmacological uses of M. vulgare include treating respiratory diseases such as acute or chronic bronchitis, colds and asthma. The plant is also used in cases where there is a lack of appetite or dyspepsia and for diagnosed type II diabetes. It has even been used for antihypertensive therapy. For decades, scientists have carried out extensive research trying to explain these and other pharmacologic actions. It is time to systematize and critically analyse the quality of results found to date. Copyright © 2016 John Wiley & Sons, Ltd.

Optimising the controlled release of dexamethasone from a new generation of PLGA-based microspheres intended for intravitreal administration.

Successful therapy for chronic diseases affecting the posterior segment of the eye requires sustained drug concentrations at the site of action for extended periods of time. To achieve this, it is necessary to use high systemic doses or frequent intraocular injections, both associated with serious adverse effects. In order to avoid these complications and improve patient's quality of life, an experimental study has been conducted on the preparation of a new generation of biodegradable poly(D,L-lactide-co-glycolide) (50:50) (PLGA) polymer microspheres (MSs) loaded with Dxm, vitamin E and/or human serum albumin (HSA). Particles were prepared according to a S/O/W encapsulation method and the 20-40µm fraction was selected. This narrow size distribution is suitable for minimally invasive intravitreal injection by small calibre needles. Characterisation of the MSs showed high Dxm loading and encapsulation efficiency (> 90%) without a strong interaction with the polymer matrix, as revealed by DSC analysis. MSs drug release studies indicated a small burst effect (lower than 5%) during the first five hours and subsequently, drug release was sustained for at least 30days, led by diffusion and erosion mechanisms. Dxm release rate was modulated when solid state HSA was incorporated into MSs formulation. SDS-PAGE analysis showed that the protein maintained its integrity during the encapsulation process, as well as for the release study. MSs presented good tolerance and lack of cytotoxicity in macrophages and HeLa cultured cells. After 12months of storage under standard refrigerated conditions (4±1°C), MSs retained appropriate physical and chemical properties and analogous drug release kinetics. Therefore, we conclude that these microspheres are promising pharmaceutical systems for intraocular administration, allowing controlled release of the drug.

Intraoperative radiation therapy opportunities for clinical practice normalization: Data recording and innovative development.

BACKGROUND: Intraoperative radiotherapy (IORT) refers to the delivery of a high dose of radiation at the time of surgery. AIM: To analyze clinical and research-oriented innovative activities developed in a 17-year period using intraoperative electron-radiation therapy (IOeRT) as a component of treatment in a multidisciplinary approach for cancer management. MATERIALS AND METHODS: From 01/1995 to 03/2012 IOeRT procedures were registered in a specific Hospital-based database. Research and developments in imaging and recording for treatment planning implementation are active since 2006. RESULTS: 1004 patients were treated and 1036 IORT procedures completed. Median age of patients was 61 (range 5 months to 94 years). Gender distribution was male in 54% of cases and female in 46%. Disease status at the time of IORT was 796 (77%) primary and 240 (23%) recurrent. Cancer type distribution included: 62% gastrointestinal, 18% sarcoma, 5% pancreas, 2% paediatric, 3% breast, 77 7% oligotopic recurrences, 2% other. IORT technical characteristics were: Applicator size 5 cm 22%, 6 cm 21%, 7 cm 21%, 8 cm 15%, 9 cm 6%, 10 cm 7% 12 cm 5% 15 cm 3%. Electron energies: 6 MeV 19%, 8 MeV 15%, 10 MeV 15%, 12 MeV 23%, 15 MeV 19%, 18 MeV 6%, other 3%. Multiple fields: 108 (11%). Dose: 7.5 Gy 3%, 10 Gy 35%, 12 Gy 3%, 12.5 Gy 49%, 15 Gy 5%, other 5%. CONCLUSION: An IORT programme developed in an Academic Hospital based on practice-oriented medical decisions is an attractive interdisciplinary oncology initiative proven to be able to generate an intensive clinical activity for cancer patient quality care and a competitive source of scientific patient-oriented research, development and innovation.

Intraoperative radiation therapy, opportunities for clinical practice normalization: MEDTING, a scientific platform.

AIM: To use a platform to analyze a subgroup specialized in evaluation of patients candidates to IOERT. BACKGROUND: Medting is a project that was initiated to support daily clinical activity, knowledge management and medical education by sharing information with other physicians. The project began at the "Hospital General Universitario Gregorio Marañón", which has a dedicated oncology physician's multi-specialist committee. There are many scientific social networks all over the world. Medting is the only platform that specializes in healthcare and has been developed for hospital purposes. MATERIALS AND METHODS: Medting brings all together the relevant clinical information from electronic medical records and picture archiving about the patient to study. Subplatform Medting-IORT was created on February 2, 2012 at the Hospital General Universitario Gregorio Marañon. It has 23 members, have been registered 18 cases with 238 multimedia images. RESULTS: Medting started with 28 physicians and five departments. After 6 months, proof of concept period, there are 225 physicians, more than 120 medical students and 39 departments in 3 hospitals using the scientific social network. Furthermore, the project is being extended on three more hospitals in Madrid. CONCLUSION: Medting gives the opportunity to oncology physicians to access all relevant clinical information with the ability to discuss case notes and view images at any time. The impact of the Medting platform in a subgroup working team to evaluate IOERT patients candidates is included in the analysis. The use of a constantly updated repository based on real cases and the documentation of the internal activity of the tumor committee beyond the medical record, has become an extraordinary tool for teaching, training and learning.