Federico Silva

Endothelial function in patients with migraine during the interictal period.

Objectives.—The aim of this study is to evaluate endothelial function in migraineur subjects during the asymptomatic period.

Double blind, randomized, placebo controlled clinical trial for the treatment of diabetic foot ulcers, using a nitric oxide releasing patch: PATHON

BackgroundDiabetes Mellitus constitutes one of the most important public health problems due to its high prevalence and enormous social and economic consequences. Diabetic foot ulcers are one of the chronic complications of diabetes mellitus and constitute the most important cause of non-traumatic amputation of inferior limbs. It is estimated that 15% of the diabetic population will develop an ulcer sometime in their lives. Although novel therapies have been proposed, there is no effective treatment for this pathology. Naturally produced nitric oxide participates in the wound healing process by stimulating the synthesis of collagen, triggering the release of chemotactic cytokines, increasing blood vessels permeability, promoting angiogenic activity, stimulating the release of epidermical growth factors, and by interfering with the bacterial mitochondrial respiratory chain. Topically administered nitric oxide has demonstrated to be effective and safe for the treatment of chronic ulcers secondary to cutaneous leishmaniasis. However, due to their unstable nitric oxide release, the topical donors needed to be applied frequently, diminishing the adherence to the treatment. This difficulty has led to the development of a multilayer polymeric transdermal patch produced by electrospinning technique that guarantees a constant nitric oxide release. The main objective of this study is to evaluate the effectiveness and safety of this novel nitric oxide releasing wound dressing for the treatment of diabetic foot ulcers.Methods and designA double-blind, placebo-controlled clinical trial, including 100 diabetic patients was designed. At the time of enrollment, a complete medical evaluation and laboratory tests will be performed, and those patients who meet the inclusion criteria randomly assigned to one of two groups. Over the course of 90 days group 1 will receive active patches and group 2 placebo patches. The patients will be seen by the research group at least every two weeks until the healing of the ulcer or the end of the treatment. During each visit the healing process of the ulcer, the patients health status and the presence of adverse events will be assessed. Should the effectiveness of the patches be demonstrated an alternative treatment would then be available to patients.Trial registrationNCT00428727.

Double blind, randomized controlled trial, to evaluate the effectiveness of a controlled nitric oxide releasing patch versus meglumine antimoniate in the treatment of cutaneous leishmaniasis [NCT00317629]

BackgroundCutaneous Leishmaniasis is a worldwide disease, endemic in 88 countries, that has shown an increasing incidence over the last two decades. So far, pentavalent antimony compounds have been considered the treatment of choice, with a percentage of cure of about 85%. However, the high efficacy of these drugs is counteracted by their many disadvantages and adverse events. Previous studies have shown nitric oxide to be a potential alternative treatment when administered topically with no serious adverse events. However, due to the unstable nitric oxide release, the topical donors needed to be applied frequently, making the adherence to the treatment difficult. The electrospinning technique has allowed the production of a multilayer transdermal patch that produces a continuous and stable nitric oxide release. The main objective of this study is to evaluate this novel nitric oxide topical donor for the treatment of cutaneous leishmaniasis.Methods and designA double-blind, randomized, double-masked, placebo-controlled clinical trial, including 620 patients from endemic areas for Leishmaniasis in Colombia was designed to investigate whether this patch is as effective as meglumine antimoniate for the treatment of cutaneous leishmaniasis but with less adverse events. Subjects with ulcers characteristic of cutaneous leishmaniasis will be medically evaluated and laboratory tests and parasitological confirmation performed. After checking the inclusion/exclusion criteria, the patients will be randomly assigned to one of two groups. During 20 days Group 1 will receive simultaneously meglumine antimoniate and placebo of nitric oxide patches while Group 2 will receive placebo of meglumine antimoniate and active nitric oxide patches. During the treatment visits, the medications will be daily administered and the presence of adverse events assessed. During the follow-up, the research group will visit the patients at days 21, 45, 90 and 180. The healing process of the ulcer, the health of the participants, recidivisms and/or reinfection will also be assessed. The evolution of the ulcers will be photographically registered. In case that the effectiveness of the patches is demonstrated, a novel and safe therapeutic alternative for one of the most important public health problems in many countries will be available to patients.

Increased plasma levels of total homocysteine but not asymmetric dimethylarginine in Hispanic subjects with ischemic stroke FREC-VI sub-study.

Background and purpose:  Despite sharing some metabolic and pathological mechanisms, the reported association between total homocysteine (tHcy), asymmetric dimethylarginine (ADMA) and stroke remains controversial, particularly in Hispanic populations from developing countries in which genetic, socioeconomic, and nutritional factors are different to those described in developed countries. Our objectives were to determine the relationships of these factors to stroke and to each other independent of other cardiovascular risk factors, and to explore potential sex differences.

Asociación entre niveles de proteína C-reactiva y óxido nítrico con el pronóstico de pacientes con infarto cerebral agudo

Introduction: Inflammation and alterations in the bioavailability of nitric oxide (NO) have been involved in the pathophysiology of cerebrovascular disease. Objective: The aim of the study was to determine the prognostic value of measuring NO metabolites and inflammatory markers in patients with acute ischemic stroke. Materials and methods: A total of 158 patients with acute ischemic stroke were included in an observational cohort study. Between 48 and 72 hours post admission, a fasting blood sample was taken to determine the biochemical profile, inflammatory markers (CRP, IL1-β, IL6, TNF-α) and nitrites/nitrates plasma levels. The cohorts follow-up was conducted for two years to determine the occurrence of a new event (stroke, myocardial infarction, heart failure) or death of vascular origin. Comparisons between groups were made using the log-rank test. A Cox multivariate regression analysis permitted to determine factors independently associated with the outcome. Result: The mean age was 70.5 ± 12.8 years. 39.2% of the subjects presented the outcome during the first 24 months of follow-up. CRP levels > 12 mg/L (HR 2.22, 95% CI 1.07-4.59) and a score > 13 on the NIHSS scale at admission (HR 2.81 95% CI 1.46-5.41) were significantly associated with an increased risk of a new event. The combination of CRP levels < 12 mg/L and nitrites/nitrates levels < 35.5 mmol/L was identified as a protective factor (HR 0.21, 95% CI 0.06-0.71). Conclusion: This study demonstrates that the determination of CRP and NOx levels could be beneficial in clinical practice to stratify the risk of future events or death of vascular origin in acute ischemic stroke patients.

Fundamentos y aplicaciones clínicas de la estimulación magnética transcraneal en neuropsiquiatríaFundamentals and Clinical Applications of Transcranial Magnetic Stimulation in Neuropsychiatry

Transcranial Magnetic Stimulation (TMS) is a non-invasive method for stimulation of brain that is based on the ability of a generated magnetic field to penetrate skull and brain meninges, inducing an electric current in the brain tissues that produces neuronal depolarization. TMS can be applied as single pulse of stimulation, pairs of stimuli separated by variable intervals to the same or different brain areas, or as trains of repetitive stimuli at various frequencies. Its mechanism of action is currently unknown. Repetitive TMS can modify the excitability of the cerebral cortex, and has been postulated as a diagnostic and therapeutic tool in the area of neuropsychiatry. The aim of this article is to review the knowledge of the TMS as regards its basic principles, pathophysiological mechanism, and its usefulness in clinical practice.Transcranial Magnetic Stimulation (TMS) is a non-invasive method for stimulation of brain that is based on the ability of a generated magnetic field to penetrate skull and brain meninges, inducing an electric current in the brain tissues that produces neuronal depolarization. TMS can be applied as single pulse of stimulation, pairs of stimuli separated by variable intervals to the same or different brain areas, or as trains of repetitive stimuli at various frequencies. Its mechanism of action is currently unknown. Repetitive TMS can modify the excitability of the cerebral cortex, and has been postulated as a diagnostic and therapeutic tool in the area of neuropsychiatry. The aim of this article is to review the knowledge of the TMS as regards its basic principles, pathophysiological mechanism, and its usefulness in clinical practice.

Fundamentos y aplicaciones clínicas de la estimulación magnética transcraneal en neuropsiquiatría

Transcranial Magnetic Stimulation (TMS) is a non-invasive method for stimulation of brain that is based on the ability of a generated magnetic field to penetrate skull and brain meninges, inducing an electric current in the brain tissues that produces neuronal depolarization. TMS can be applied as single pulse of stimulation, pairs of stimuli separated by variable intervals to the same or different brain areas, or as trains of repetitive stimuli at various frequencies. Its mechanism of action is currently unknown. Repetitive TMS can modify the excitability of the cerebral cortex, and has been postulated as a diagnostic and therapeutic tool in the area of neuropsychiatry. The aim of this article is to review the knowledge of the TMS as regards its basic principles, pathophysiological mechanism, and its usefulness in clinical practice.Transcranial Magnetic Stimulation (TMS) is a non-invasive method for stimulation of brain that is based on the ability of a generated magnetic field to penetrate skull and brain meninges, inducing an electric current in the brain tissues that produces neuronal depolarization. TMS can be applied as single pulse of stimulation, pairs of stimuli separated by variable intervals to the same or different brain areas, or as trains of repetitive stimuli at various frequencies. Its mechanism of action is currently unknown. Repetitive TMS can modify the excitability of the cerebral cortex, and has been postulated as a diagnostic and therapeutic tool in the area of neuropsychiatry. The aim of this article is to review the knowledge of the TMS as regards its basic principles, pathophysiological mechanism, and its usefulness in clinical practice.

Complicaciones neurológicas de la endocarditis infecciosa: controversias

En la endocarditis infecciosa aguda se describen complicaciones neurologicas entre 20% y 40% de los casos, lo cual representa un importante factor que predice morbimortalidad, secuelas y discapacidad. Esta entidad se caracteriza por un amplio espectro clinico debido a su compleja fisiopatologia, que involucra entre otros, fenomenos inflamatorios, inmunes, infecciosos y embolicos. A pesar de la notable frecuencia de las complicaciones neurologicas en la endocarditis infecciosa, dadas especialmente por enfermedad cerebrovascular y neuroinfecciones, aun existen controversias acerca de algunos aspectos diagnosticos y terapeuticos, en parte por la poca evidencia disponible, las cuales se discuten a continuacion, a partir de una serie de casos atendidos en la Fundacion Cardiovascular de Colombia.