Listeria monocytogenesy mecanismo de caballo de Troya a través de la barrera hematoencefálica / isteria monocytogenesand Trojan horse mechanism across the blood-brain barrier

Las infecciones del sistema nervioso central son potencialmente mortales, causadas por patógenos, como bacterias, virus y hongos. Para llegar hasta el cerebro, los microorganismos utilizan diversas vías y formas. Este patogeno es una bacteria grampositiva corta, flagelar e intracelular, con la capacidad de inducir su internalización en células fagocíticas (monocitos/macrófagos) y no fagocíticas (células endoteliales). Al infectar los macrófagos, estos microorganismos se valen de su capacidad de fijación, adhesión y migración transendotelial, para cruzar la barrera hematoencefálica, finalmente, generando meningitis bacteriana. En esta revisión describimos el mecanismo de caballo de Troya usado por Listeria monocytogenespara invadir el cerebro en el desarrollo de enfermedades infecciosas e incorporamos nuevos conocimientos sobre moléculas que intervienen en dicho mecanismo(AU)

Central nervous system infections are life-threatening, caused by pathogens such as bacteria, viruses and fungi. To access the brain, microorganisms use various mechanisms. Listeria monocytogenes is a short, flagellar and intracellular gram-positive bacterium, with the ability to induce its internalization in phagocytic (monocytes/macrophages) and non-phagocytic (endothelial cells) cells. By infecting macrophages, these microorganisms take advantage of their binding, adhesion, and transendothelial migrationcapacity to cross the blood-brain barrier, finally generating bacterial meningitis. In this review we describe the Trojan horse mechanism used by Listeria monocytogenesto invade the brain in the development of infectious diseases and we incorporate new knowledge about molecules that intervene in this mechanism(AU)

Nanocannabinoides como terapia frente a glioma / Nannocannabinoids for brain tumor drug delivery

Las patologías cerebrales representan un desafío terapéutico por la restricción al paso de fármacos a través de la barrera hematoencefálica. Por ello, actualmente se persigue diseñar transportadores de fármacos capaces de atravesar de manera eficiente el endotelio cerebral tras su administración intravenosa. Sin embargo, el impacto traslacional de la nanomedicina es aún discreto. Sin duda, la transición de un desarrollo empírico hacia un diseño racional adecuado a las necesidades terapéuticas concretas en cada caso aumentará las posibilidades de éxito.Bajo esta premisa y aprovechando tanto el tropismo cerebral como la actividad antiproliferativa del cannabidiol, y a fin de contribuir al diseño racional de nanocápsulas dirigidas para el tratamiento de gliomas, hemos evaluado la influencia de distintos parámetros en su comportamiento in vitro e in vivo. Efectivamente, hemos demostrado que tanto el paso a través de barrera hematoencefálica como la captación por células de glioma, así como la velocidad de liberación de fármacos pueden modularse variando su tamaño de partícula. El método térmico de inversión de fases posibilita la obtención de nanocápsulas bajo demanda en términos de tamaño gracias al modelo matemático lineal en una variable aquí descrito.Además, hemos desarrollado una novedosa estrategia de vectorización con cannabidiol (que incluso supera a otras que ya se encuentran en ensayos clínicos). Asimismo, las nanocápsulas sirven como transportadores de liberación prolongada del cannabidiol, superando así sus problemas de formulación que venían limitando su potencial terapéutico.En conjunto, las nanocápsulas lipídicas, cargadas y funcionalizadas con cannabidiol, constituyen prometedores candidatos para el tratamiento de gliomas. (AU)

Brain diseases are a major health challenge as brain drug delivery is truly hindered by the blood-brain barrier. Therefore, targeted drug nanocarriers arise as an alternative to achieve efficient transport across the brain endothelium following minimally-invasive intravenous injection. However, the global translational impact of nanomedicine remains modest. Certainly, the transition from empirical development towards a rational design tailored to the specific disease needs is likely to improve the chances of success.Under this assumption and taking advantage of both the natural brain tropism and the antiproliferative activity of cannabidiol, to contribute to the rational design of targeted nanocapsules for glioma therapy, we have thoroughly screened the influence of distinct parameters on their in vitro and in vivo behaviour. Effectively, we have demonstrated that both the brain and glioma targeting ability and the drug release rate can be tailored by varying the particle size of the nanocapsules. This fine size-tailoring can be achieved by the phase inversion temperature method thanks to the hereindescribed linear univariate mathematical model as a function of the oily phase/surfactant mass ratio.Moreover, we have introduced, on the one hand, a pioneering brain tumor targeting strategy with cannabidiol (with better targeting properties than other strategies that have already reached the clinical trials stage) and, on the other hand, nanocapsules as extendedrelease carriers of cannabidiol to overcome the formulation problems that have traditionally constrained its therapeutic potential.Altogether, small lipid nanocapsules loaded and functionalized with cannabidiol arise as promising dually-targeted candidates for intravenous treatment of glioma. (AU)

Importancia de la tripanosomiasis africana para Cuba / Importance of African Trypanosomiasis for Cuba

Introducción: La tripanosomiasis africana humana es producida por protozoos del género Trypanosoma y transmitida fundamentalmente por la picadura de la mosca tse-tsé. En el último siglo ha habido varias epidemias en el África, pero dado que el número de nuevos casos notificados había disminuido, la hoja de ruta de la OMS para las enfermedades tropicales desatendidas fijó el objetivo de su eliminación como problema de salud pública para 2020. Muchos de los países donde Cuba presta colaboración internacionalista son endémicos, por lo que los colaboradores están expuestos al riesgo de padecer y enfrentar esta enfermedad. Objetivo: Realizar una actualización clínica y epidemiológica de la entidad para alertar sobre la posibilidad de la aparición en áreas endémicas y la presencia de casos importados en Cuba. Métodos: Se realizó una revisión bibliográfica en la base de datos Medline/PubMed y en artículos relevantes relacionados con el tema, de los últimos años; también hemos tomado como referencia las notas descriptivas de tripanosomiasis africana de la OMS en el 2020, así como textos clásicos de medicina interna y la plataforma búsqueda ClinicalKey. Información, análisis y síntesis: Se hizo una detallada exposición de la enfermedad y la conducta terapéutica; una breve reseña de los casos importados y del país de procedencia, además del peligro que presenta la aparición de casos importados para Cuba. Conclusiones: La enfermedad es una entidad potencialmente mortal, endémica en países donde existe colaboración cubana. Es necesario tener presente el diagnóstico de esta enfermedad para un abordaje terapéutico adecuado(AU)

Introduction: Human African trypanosomiasis is produced by protozoa of the genus Trypanosoma and transmitted mainly by the bite of the tsetse fly. There have been several epidemics in Africa in the last century, but as the number of new reported trypanosomiasis cases has decreased, the WHO roadmap for neglected tropical diseases had targeted their elimination as a public health problem by 2020. Many of the countries where Cuba provides internationalist collaboration are endemic, so the collaborators are exposed to the risk of suffering and facing this disease. Objectives: To carry out a clinical and epidemiological update of the entity and warn about the possibility of the appearance in endemic areas and the presence of imported cases in Cuba. Methods: a bibliographic review was carried out in the Medline / Pub Med database and in relevant articles related to the subject, from recent years; we have taken the 2020 WHO African Trypanosomiasis descriptive notes as a reference, as well as classic internal medicine texts and the ClinicalKey search platform. Information, Analysis and Synthesis: A detailed exposition of the disease and the therapeutic behavior was made; a brief review of imported cases and the country of origin, in addition to the danger posed by the appearance of imported cases for Cuba. Conclusions: This is a potentially fatal entity, endemic in countries where there is Cuban collaboration. It is necessary to bear in mind the diagnosis of this disease for an adequate therapeutic approach(AU)

The role of astrocytes in multiple sclerosis pathogenesis. / Participación de los astrocitos en la patogénesis de la esclerosis múltiple.

INTRODUCTION: Multiple sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system (CNS), in which astrocytes play an important role as CNS immune cells. However, the activity of astrocytes as antigen-presenting cells (APC) continues to be subject to debate. DEVELOPMENT: This review analyses the existing evidence on the participation of astrocytes in CNS inflammation in MS and on several mechanisms that modify astrocyte activity in the disease. CONCLUSIONS: Astrocytes play a crucial role in the pathogenesis of MS because they express toll-like receptors (TLR) and major histocompatibility complex (MHC) classI andII. In addition, astrocytes participate in regulating the blood-brain barrier (BBB) and in modulating T cell activity through the production of cytokines. Future studies should focus on the role of astrocytes in order to find new therapeutic targets for the treatment of MS.

Vascular pathology: Cause or effect in Alzheimer disease? / Patología vascular: ¿causa o efecto en la enfermedad de Alzheimer?

INTRODUCTION: Alzheimer disease (AD) is the main cortical neurodegenerative disease. The incidence of this disease increases with age, causing significant medical, social and economic problems, especially in countries with ageing populations. OBJECTIVE: This review aims to highlight existing evidence of how vascular dysfunction may contribute to cognitive impairment in AD, as well as the therapeutic possibilities that might arise from this evidence. DEVELOPMENT: The vascular hypothesis emerged as an alternative to the amyloid cascade hypothesis as an explanation for the pathophysiology of AD. This hypothesis locates blood vessels as the origin for a variety of pathogenic pathways that lead to neuronal damage and dementia. Destruction of the organisation of the blood brain barrier, decreased cerebral blood flow, and the establishment of an inflammatory context would thus be responsible for any subsequent neuronal damage since these factors promote aggregation of ß-amyloid peptide in the brain. The link between neurodegeneration and vascular dysfunction pathways has provided new drug targets and therapeutic approaches that will add to the treatments for AD. CONCLUSIONS: It is difficult to determine whether the vascular component in AD is the cause or the effect of the disease, but there is no doubt that vascular pathology has an important relationship with AD. Vascular dysfunction is likely to act synergistically with neurodegenerative changes in a cycle that exacerbates the cognitive impairment found in AD.

Meningitis bacteriana y viral / Bacterial and viral meningitis

La meningitis es una enfermedad cuya importancia es de Salud Pública, no solo por su incidencia, sino también por su mortalidad y secuelas en quienes la padecen. El Sistema Nervioso Central está protegido de manera especial, sin embargo los microorganismos se las ingenian para evadir las defensas; al ser infectadas las meninges, se inicia la respuesta del sistema inmune, piedra angular en la fisiopatología. La manifestación clínica puede ser muy florida, sin embargo es importante reconocer los signos claves para la sospecha oportuna y la realización de exámenes complementarios esenciales en el diagnóstico, tal como la punción lumbar; no se debe olvidar reconocer aquel paciente que previo a este procedimiento, debe de realizarse un estudio de imágenes; a pesar de esto, el inicio de los antibióticos y el uso de glucocorticoide no puede ser retrasado, y se debe administrar en el menor tiempo posible, fundamental para un mejor pronóstico del paciente.

Meningitis is a disease which is of Public Health importance, not only for its incidence, but also its mortality and sequelae in patients. The Central Nervous System is protected in a special way; however microorganisms manage to evade the defenses. When the Meninges are infected, the Immune System's response begins, of great significance in the pathophysiology. The clinical manifestations may be many, but it is important to recognize the key signs for suspicion and timely implementation of essential complementary tests in the diagnosis, such as lumbar puncture.It is vital to recognize the patient prior to the procedure, needs an imaging study. Despite this, the beginning of antibiotics and the use of glucocorticoid must not be delayed and should be administered as soon as possible, essential to a better prognosis.

Morphological and morphometric changes in rat optic nerve microvessels in a glaucoma experimental model.

AIM: To study the morphological and morphometric changes produced in the capillaries of the optic nerve (ON) head and initial portion after the experimental increase in intraocular pressure (IOP). MATERIAL AND METHODS: Wistar rats underwent cauterization of three episcleral veins, which produced an immediate increase in the IOP, and was maintained for 3 months. Sagittal sections of the eyeball were studied with immunohistochemical techniques, using a primary antibody to GLUT-1. The GLUT-1 positive capillaries were counted, and measurements were made of the area, perimeter and mean diameter. RESULTS: Microscopic examination of sections of the ON of control rats revealed a lower density and larger caliber of capillaries in the prelaminar region as compared with the other regions of the ON (P<.05). Comparison between the control and the experimental groups showed a reduction in capillary density (except in the prelaminar region) and a smaller size in all the areas of the ON studied, but less evident in the initial portion (P<.05). CONCLUSIONS: The increase in IOP was associated with significant qualitative and quantitative changes in the capillaries of the laminar and poslaminar regions of the ON head. These changes appear to return towards parameters compatible with normality in the initial portion of the ON, an area where the vascular collapse was less evident. These findings might explain the significant reduction in ocular blood flow seen in patients with primary open-angle glaucoma.

[Hepatic encephalopathy]. / Encefalopatía hepática.

Hepatic encephalopathy (EH) is a severe complication of hepatic cirrhosis that is characterized by multiple neuropsychiatric manifestations. EH is usually triggered by a precipitating factor and occurs in patients with severely impaired hepatic function. Minimal EH is characterized by minor cognitive impairments that are difficult to specify but represent a risk for the patients. The primary pathophysiological mechanism of EH is considered to be an increase in blood ammonia with an impairment in the patency of the blood-brainbarrier and its metabolism to glutamine in astrocytes. The diagnosis is clinical and neuroimaging techniques can be complementary. The diagnosis of minimal EH requires specific neurocognitive tests. The clinical evaluation should be directed towards identifying the trigger. Nonabsorbable disaccharides and rifaximin constitute the treatment of choice, along with prophylaxis for new episodes.

Permeabilidad de la barrera hematoencefálica en tumores endocraneanos evaluada con técnica de realce dinámico con contraste-T1W IRM. Serie de casos / Blood-Brain Barrier Permeability in Intracranial Tumors Assessed by Dynamic Contrast-Enhanced T1W MRI. Series of Cases

Entender el funcionamiento de la barrera hematoencefálica (BHE) tiene importantes implicaciones, no solo en la detección de enfermedades, sino también en el desarrollo de nuevos tratamientos. Los estudios de la permeabilidad mediante imágenes por resonancia magnética (IRM) se enfocan en medir el grado de disrupción de la BHE usando una técnica de análisis de imágenes dinámicas con contraste. En este artículo se revisan los conceptos básicos de esta técnica y se presentan seis pacientes con patología tumoral endocraneana, en quienes se realiza esta evaluación con el objetivo de ilustrar su utilidad clínica.

Understanding the brain blood barrier (BBB) has significant implications for disease detection and in the development of new treatments. Magnetic resonance imaging permeability studies measure the degree of BBB disruption, employing an analytical technique of dynamic contrast-enhanced imaging. In this article, we review the basic concepts of this technique, and six patients with endocranial tumor pathology are presented. These patients undergo this evaluation with the purpose of illustrating its clinical usefulness.

Lesiones intracerebrales que no realzan con el gadolinio: a propósito de un caso de criptococoma en un paciente con sida / Brain diseases that do not enhance with gadolinium: a case about a patient with AIDS and an intracerebral cryptococcoma

El gadolinio se usa como complemento importante en neuroimágenes para una adecuada visualización y caracterización de procesos neoplásicos e inflamatorios. Cuando hay un aumento de la permeabilidad capilar, ya sea por vasodilatación o por ruptura de la barrera hematoencefálica, o cuando hay una importante neovascularización en una lesión, habrá un paso anormal o un aumento en la cantidad de medio de contraste local. Cuando la barrera hematoencefálica permanece íntegra o cuando no hay un aumento en la vascularización focal, no habrá una acumulación o un aumento en la cantidad medio de contraste intralesional. En este artículo de revisión se describe el caso clínico de un paciente de 56 años de edad con sida que presenta una meningitis por criptococo y un criptococoma intraparenquimatoso. Se describen los hallazgos por resonancia magnética de los criptococomas y, además, se realiza una revisión de las patologías más frecuentes, cuya ausencia de realce tras la administración del gadolinio es característica.

Gadolinium is used as an important complement in neuroimaging for an adequate visualization and characterization of neoplastic and inflammatory processes. When there is an increased capillary permeability because of vasodilation or blood brain barrier breakdown or when new capillaries are developed in an injury, there will be an abnormal enhancement of local tissues. When the blood brainbarrier remains intact or if there is not an increased vacularization, there will not be an accumulation or increase in the amount of local contrast medium. This review article describes the case of a 56 year old patient with aids with a cryptococcal meningitis and intraparenchymal cryptococcoma. There is a description of the mRi findings of cryptococcoma and a review of the most frequent pathologies in which lack of enhancement after gadolinium administration is characteristic.