Plant-Derivatives Small Molecules with Antibacterial Activity.

The vegetal world constitutes the main factory of chemical products, in particular secondary metabolites like phenols, phenolic acids, terpenoids, and alkaloids. Many of these compounds are small molecules with antibacterial activity, although very few are actually in the market as antibiotics for clinical practice or as food preservers. The path from the detection of antibacterial activity in a plant extract to the practical application of the active(s) compound(s) is long, and goes through their identification, purification, in vitro and in vivo analysis of their biological and pharmacological properties, and validation in clinical trials. This review presents an update of the main contributions published on the subject, focusing on the compounds that showed activity against multidrug-resistant relevant bacterial human pathogens, paying attention to their mechanisms of action and synergism with classical antibiotics.

Cell polarity protein Spa2 coordinates Chs2 incorporation at the division site in budding yeast.

Deposition of additional plasma membrane and cargoes during cytokinesis in eukaryotic cells must be coordinated with actomyosin ring contraction, plasma membrane ingression and extracellular matrix remodelling. The process by which the secretory pathway promotes specific incorporation of key factors into the cytokinetic machinery is poorly understood. Here, we show that cell polarity protein Spa2 interacts with actomyosin ring components during cytokinesis. Spa2 directly binds to cytokinetic factors Cyk3 and Hof1. The lethal effects of deleting the SPA2 gene in the absence of either Cyk3 or Hof1 can be suppressed by expression of the hypermorphic allele of the essential chitin synthase II (Chs2), a transmembrane protein transported on secretory vesicles that makes the primary septum during cytokinesis. Spa2 also interacts directly with the chitin synthase Chs2. Interestingly, artificial incorporation of Chs2 into the cytokinetic machinery allows the localisation of Spa2 at the site of division. In addition, increased Spa2 protein levels promote Chs2 incorporation at the site of division and primary septum formation. Our data indicate that Spa2 is recruited to the cleavage site to co-operate with the secretory vesicle system and particular actomyosin ring components to promote the incorporation of Chs2 into the so-called 'ingression progression complexes' during cytokinesis in budding yeast.

[Stereology as a tool to estimate brain volume and cortical atrophy in elders with dementia]. / La estereología como herramienta de cuantificación del volumen y la atrofia cortical en el cerebro del anciano con demencia.

INTRODUCTION: stereology is a body of methods that allow unbiased and efficient estimation of geometric quantities defined in arbitrary physical structures. In particular, stereology is a valuable tool to assist neuroimaging in the estimation of morphometric parameters in the brain. Therefore, stereology may confer objectivity in the complementary and diagnostic evaluation of dementia by adding disease by adding quantitative data to clinical evaluation. OBJECTIVES AND METHODS: our purpose was to illustrate estimation of brain volume and pial surface area by means of quantitative, computer-assisted stereological methods. Both parameters were estimated by means of a vertical design with a single series of parallel Cavalieri sections at a random orientation and perpendicular to a fixed horizontal plane. The sections were obtained by magnetic resonance imaging. Suitable test systems (of test points for volume, and of cycloids for surface area) were superimposed on these sections with the aid of special software. RESULTS: to explore the statistical error of the volume estimator due to stereological sampling, 5 or 10 systematic sections were used in combination with two test point densities in a ratio of 1:4, so that the workload varied in the proportions 1:2:4:8. The four resulting estimators varied between 986 and 1120 cm(3). The surface area estimators varied between 1947 and 2096 cm(2), with workloads varying in the proportions of 1:2:2.3:4.6. CONCLUSIONS: stereology is a simple and efficient tool to obtain objective brain volume and surface area estimators that are unbiased by design and accurate at a modest cost. Thus the corresponding methods can effectively assist in diagnostic and follow-up evaluation of elders with dementia.

La estereología como herramienta de cuantificación del volumen y la atrofia cortical en el cerebro del anciano con demencia / Stereology as a tool to estimate brain volume and cortical atrophy in elders with dementia

Introducción: la estereología es un conjunto de métodos que permiten la estimación insesgada y eficiente de cantidades geométricas definidas en estructuras arbitrarias. En particular, es una herramienta útil en la cuantificación de parámetros morfométricos cerebrales en estudios de neuroimagen. Por tanto, la estereología puede aportar una mayor objetividad en la evaluación complementaria y diagnóstica de ancianos con demencia, añadiendo datos cuantitativos a la evaluación clínica. Objetivos y métodos: nuestro objetivo es ilustrar la estimación del volumen cerebral y el área superficial de la corteza cerebral de un paciente anciano mediante procedimientos estereológicos cuantitativos asistidos por ordenador. Para estimar ambos parámetros se utilizó un diseño vertical con una serie de secciones paralelas de Cavalieri con orientación aleatoria y perpendiculares a un plano horizontal fijo. Las secciones se obtuvieron mediante resonancia magnética nuclear. Sobre ellas se superpusieron sondas sistemáticas (de puntos para el volumen y de cicloides para la superficie) mediante un software especial. Resultados: con objeto de explorar la variabilidad del error estadístico de las estimaciones, se utilizaron 5 o 10 secciones sistemáticas combinadas con dos densidades de puntos de sonda en la relación 1:4, de tal manera que el trabajo invertido varió en la relación 1:2:4:8. Los cuatro estimadores obtenidos variaron entre 986 y 1.120 cm3. Por otra parte, para el área de la superficie pial los estimadores variaron entre 1.947 y 2.096 cm2, con cargas de trabajo variables en la relación 1:2:2.3:4.6. Conclusiones: la estereología es una herramienta sencilla y eficiente, capaz de proporcionar estimaciones objetivas, no sesgadas por diseño, del volumen y la superficie cerebral pial con un coste modesto. Ello puede contribuir a facilitar la evaluación diagnóstica, evolutiva y pronóstica de pacientes ancianos con demencia

Introduction: stereology is a body of methods that allow unbiased and efficient estimation of geometric quantities defined in arbitrary physical structures. In particular, stereology is a valuable tool to assist neuroimaging in the estimation of morphometric parameters in the brain. Therefore, stereology may confer objectivity in the complementary and diagnostic evaluation of dementia by adding disease by adding quantitative data to clinical evaluation. Objectives and methods: our purpose was to illustrate estimation of brain volume and pial surface area by means of quantitative, computer-assisted stereological methods. Both parameters were estimated by means of a vertical design with a single series of parallel Cavalieri sections at a random orientation and perpendicular to a fixed horizontal plane. The sections were obtained by magnetic resonance imaging. Suitable test systems (of test points for volume, and of cycloids for surface area) were superimposed on these sections with the aid of special software. Results: to explore the statistical error of the volume estimator due to stereological sampling, 5 or 10 systematic sections were used in combination with two test point densities in a ratio of 1:4, so that the workload varied in the proportions 1:2:4:8. The four resulting estimators varied between 986 and 1120 cm3. The surface area estimators varied between 1947 and 2096 cm2, with workloads varying in the proportions of 1:2:2.3:4.6. Conclusions: stereology is a simple and efficient tool to obtain objective brain volume and surface area estimators that are unbiased by design and accurate at a modest cost. Thus the corresponding methods can effectively assist in diagnostic and follow-up evaluation of elders with dementia (AU)

Chondroitinase ABC has a long-lasting effect on chondroitin sulphate glycosaminoglycan content in the injured rat brain.

Chondroitin sulphate proteoglycans (CSPGs) are axon growth inhibitory molecules present in the glial scar that play a part in regeneration failure after damage to the CNS and which restrict CNS plasticity. Removal of chondroitin sulphate glycosaminoglycan (GAG) chains with chondroitinase-ABC (chABC) in models of CNS injury promotes both axon regeneration and plasticity. We have analysed the immediate and long-term effects of a single injection of chABC on CSPGs, GAGs and axon regeneration. We made unilateral nigrostriatal lesions in adult rats accompanied by an adjacent infusion of either chABC or a bacterial-derived control enzyme (penicillinase). Within 24 h of chABC treatment there was digestion of GAGs, including hyaluronan, and a reduction in neurocan in an area extending 1.5 mm around the injection site. Around 50% of GAG is inaccessible to chABC digestion, even in tissue digested in vitro, which probably represents intracellular stores. In control penicillinase treated animals, total GAGs recovered from the lesioned brains were up-regulated by 4-fold 7 days after injury and gradually decreased to normal at 28 days post-lesion. In chondroitinase-treated animals, the total GAG remained at low level throughout the 28-day experimental period. This suggests the persistence of active chABC for at least 10 days after injection which is able to digest CSPGs released from cells during this time. This was confirmed by immunological detection of enzyme for 10 days and by retrieval of active enzyme from the brain at 10 days after injection. Our results suggest that a single injection of chABC can produce an environment conducive to CNS repair for over 10 days.

How does chondroitinase promote functional recovery in the damaged CNS?

A number of recent studies have established that the bacterial enzyme chondroitinase ABC promotes functional recovery in the injured CNS. The issue of how it works is rarely addressed, however. The effects of the enzyme are presumed to be due to the degradation of inhibitory chondroitin sulphate GAG chains. Here we review what is known about the composition, structure and distribution of the extracellular matrix in the CNS, and how it changes in response to injury. We summarize the data pertaining to the ability of chondroitinase to promote functional recovery, both in the context of axon regeneration and the reactivation of plasticity. We also present preliminary data on the persistence of the effects of the enzyme in vivo, and its hyaluronan-degrading activity in CNS homogenates in vitro. We then consider precisely how the enzyme might influence functional recovery in the CNS. The ability of chondroitinase to degrade hyaluronan is likely to result in greater matrix disruption than the degradation of chondroitin sulphate alone.

The neurosecretory system is hypertrophied in senescence-accelerated mice.

The hypothalamic supraoptic and paraventricular nuclei form the neurosecretory system and synthesize the neurohormones oxytocin and arginine-vasopressin. The senescence-accelerated mouse is a model of rapid aging that displays senile amyloidosis and memory problems. This paper presents the characterization of the neurosecretory system and describes the presence of a bilateral constant cluster of neurosecretory neurons in these mice. The stereologic analysis revealed that these groups contain 197 +/- 18 cells (87% synthesize arginine-vasopressin and 13% oxytocin). The presence of these clusters of neurosecretory neurons suggests that these mice could present greater neurohormone synthesis, increasing the deleterious effects of accelerated aging in this strain.

El sistema neurosecretor del ratón de envejecimiento acelerado: un modelo de deterioro cognitivo / The neurosecretory system of the senescence-accelerated mouse: a model of cognitive decline

Introducción: el ratón de envejecimiento acelerado (senescence-accelerated mouse [SAM]) es un modelo de ciclo vital breve. Una vez alcanza la edad reproductiva, comienza un rápido envejecimiento que cursa con deterioro cognitivo. El sistema neurosecretor del hipotálamo está formado por los núcleos supraóptico y paraventricular, cuyas neuronas sintetizan las hormonas oxitocina y vasopresina. Una característica del hipotálamo del SAM es la presencia de un núcleo que no aparece en otras cepas de ratones, el núcleo accesorio. Se analiza el hecho de que los valores elevados de neurohormonas pueden participar en los procesos de envejecimiento y deterioro cognitivo. Material y métodos: hemos utilizado ratones de ambos sexos de la cepa SAM en sus 2 variedades; de pronto envejecimiento (SAM-P8), que tienen un ciclo vital de unos 12 meses, y de envejecimiento retardado (SAM-R1), que viven unos 17 meses. Además, para comparar los resultados utilizamos ratones de las cepas Swiss y AKR/J. Se perfundió a los animales y se utilizaron las técnicas de tionina, inmunocitoquímicas (oxitocina y vasopresina) y DiI para analizar las proyecciones hipotalámicas. Los estudios cuantitativos del número de neuronas se realizaron por medio de un análisis estereológico. Resultados: la característica principal del hipotálamo de los ratones SAM es la presencia del núcleo accesorio que no aparece en las otras cepas analizadas. Este núcleo posee unas 200 neuronas, que en su mayoría sintetizan vasopresina y sólo unas pocas (13%), oxitocina. Conclusiones: los resultados obtenidos en esta cepa de ratones de envejecimiento acelerado se relacionan con el hecho observado en humanos de que las neuronas neurosecretoras del hipotálamo se caracterizan por un incremento de su actividad en la etapa de envejecimiento y en ciertos trastornos neuropatológicos

Introduction: the senescence-accelerated mouse (SAM) is a murine model of rapid ageing once adulthood has been reached and there is a concomitant cognitive decline. The neurosecretory system of the hypothalamus is composed of the supraoptic and paraventricular nuclei, and their neurons synthesize the hormones oxytocin and vasopressin. A feature of the SAM is the presence of a well developed nucleus that does not appear in other mice strains, the accessory nucleus. The increase in neurosecretory hormone levels could play a role in the processes of ageing and cognitive decline. Material and methods: we used male and female mice of the two strains of SAM: ageing prone SAM-P8 (average life expectancy 12 months) and retarded SAM-R1 (average life expectancy 17 months). To compare our observations, we used several mice of the Swiss and AKR/J strains. After perfusion, several techniques were employed to analyse the hypothalamus of these mice; thionin, immunocytochemistry (oxytocin and vasopressin) and DiI to observe hypothalamic projections. The quantitative analysis was performed by a stereology approach. Results: the most interesting result observed was the presence of the accessory nucleus in SAM mice. This nucleus consists of an arrangement of some 200 neurons. Most of these neurons were vasopressinergic and some (13%) were oxytocinergic. Conclusions: the results obtained in this strain of accelerated senescence are in agreement with those reported in the aged human brain, in which there is an increase in the synthesis of these neurohormones, both in normal and some neuropathological conditions

¿Pueden las autoevaluaciones del alumnado ser la nota final de una asignatura): el caso de biogerontología / Is it possible to assume the autoevaluation of the students as the final mark of a subject?: the case of Biogerontology

Presentamos un estudio de la correlación entre las calificaciones objetivas (CO) en una prueba tipo test de los estudiantes en la asignatura optativa Biogerontología con las autoevaluaciones subjetivas (AS) que los alumnos se asignaron tras la realización de la prueba y la que consideraron se merecían con relación al esfuerzo (AE) realizado para preparar dicha materia. El estadístico utilizado ha sido el coeficiente de correlación (rxy). Los resultados obtenidos muestran una alta correlación rxy=0,77 cuando se comparan AS-AE. Sin embargo, rxy es muy bajo para los pares de valores CO-AS (0,05) y CO-AE (-0,07). Existen diferencias significativas (p<0,05) cuando se comparan los pares de valores CO-AS y CO-AE, mientras que no hay diferencia al comparar AS-AE. Los resultados de este estudio sugieren que las valoraciones AS y AE no pueden ser utilizadas como criterio final de calificación en este grupo de estudiantes por presentar ambas una correlación muy baja con respecto a la CO obtenida en la prueba de examen (AU)

Estudio de la correlación entre las calificaciones en la asignatura Biología Celular y Tisular y las de las pruebas de acceso a la Universidad en un grupo de estudiantes de medicina / Correlation marks in the subject Cell and Tissue Biology and those obtained in the University entrance examination in a group of students of medicine

Presentamos un estudio de correlación entre las calificaciones de los estudiantes de la asignatura Biología Celular y Tisular, con las que obtuvieron en el bachillerato y para ingresar en la facultad de medicina. El estadístico empleado fue el coeficiente de correlación (rxy). Los resultados obtenidos ponen de manifiesto que existe una correlación media-baja cuando se comparan dichas calificaciones. El valor más alto se obtiene al comparar la asignatura con la nota final de acceso a la Universidad (rxy = 0,512; p < 0,05) (AU)