The ROCK inhibitor Fasudil prevents chronic restraint stress-induced depressive-like behaviors and dendritic spine loss in rat hippocampus

Indexación: Web of Science; Scopus.Background: Dendritic arbor simplification and dendritic spine loss in the hippocampus, a limbic structure implicated in mood disorders, are assumed to contribute to symptoms of depression. These morphological changes imply modifications in dendritic cytoskeleton. Rho GTPases are regulators of actin dynamics through their effector Rho kinase. We have reported that chronic stress promotes depressive-like behaviors in rats along with dendritic spine loss in apical dendrites of hippocampal pyramidal neurons, changes associated with Rho kinase activation. The present study proposes that the Rho kinase inhibitor Fasudil may prevent the stress-induced behavior and dendritic spine loss. Methods: Adult male Sprague-Dawley rats were injected with saline or Fasudil (i.p., 10 mg/kg) starting 4 days prior to and maintained during the restraint stress procedure (2.5 h/d for 14 days). Nonstressed control animals were injected with saline or Fasudil for 18 days. At 24 hours after treatment, forced swimming test, Golgi-staining, and immuno-western blot were performed. Results: Fasudil prevented stress-induced immobility observed in the forced swimming test. On the other hand, Fasudiltreated control animals showed behavioral patterns similar to those of saline-treated controls. Furthermore, we observed that stress induced an increase in the phosphorylation of MYPT1 in the hippocampus, an exclusive target of Rho kinase. This change was accompanied by dendritic spine loss of apical dendrites of pyramidal hippocampal neurons. Interestingly, increased pMYPT1 levels and spine loss were both prevented by Fasudil administration. Conclusion: Our findings suggest that Fasudil may prevent the development of abnormal behavior and spine loss induced by chronic stress by blocking Rho kinase activity.https://academic.oup.com/ijnp/article/20/4/336/263217

AVANCES EN EL ESTUDIO DE LA PATOGÉNESIS Y PREVENCIÓN DE LA ENTEROTOXEMIA DE LAS ALPACAS.

The results of our recent research work on enterotoxemia in Peruvian alpacas are presented. Microbiological and molecular analyses found that the majority of the isolates corresponded to Clostridium perfringens and contained the cpa coding gene for α toxin (A genotype) while 0.4% contained both the cpa and cpb genes of the α and β toxins (C genotype). A parallel study revealed that 8.5% of the genotype A isolates also had cpb2, but the cpe (enterotoxin) gene was absent in all cases. These results highly suggest that the exotoxins secreted by C. perfringens are the virulent factors in enterotoxemia, rather than the endogenous enterotoxin. Additionally, an histopathological study of intestinal samples from fatal cases showed that 30.6% had abundant immature structures of Eimeria macusaniensis affecting deep mucosa and cryptic gland epithelia, primarily in the jejune and ileum, suggesting that eimeriosis is likely a triggering or predisposing factor for the development of enterotoxemia. The microbiological studies allowed the design and progressive improvement of an inactivated enterotoxemia vaccine containing primarily the bacterial component plus exotoxins of types A, Aβ2 and C isolated from natural fatal cases of the disease. During six years of field tests in southern Peru, the vaccine has steadily reduced specific neonatal mortality rates due to enterotoxemia from 19.5% (2000, without vaccine) to less than 5% in 2006.Se revisan las investigaciones recientes realizadas por nuestro grupo de investigadores sobre enterotoxemia de las alpacas en el Perú. Estudios microbiológicos y moleculares demostraron que la mayoría de las cepas aisladas fueron de Clostridium perfringens y estas contienen únicamente el gen cpa de la toxina α (C. perfringens genotipo A) y solamente el 0.4% tienen genes cpa y cpb de las toxinas α y β (genotipo C). En análisis paralelo, se encontró que el 8.5% de los genotipos A contenían, adicionalmente, el gen cpb2, pero ninguna cepa tenía el gen cpe de la enterotoxina. Estos resultados evidencian que las exotoxinas secretadas, y no las endotoxinas (cpe), serían los probables factores de virulencia clostridiales en la enterotoxemia de la alpaca. Adicionalmente, en el análisis histopatológico de intestinos infectados, el 30.6% de las muestras presentó abundantes estructuras parasitarias inmaduras correspondientes a Eimeria macusaniensis, afectando la mucosa y epitelio de las glándulas crípticas intestinales, sugiriendo a las infecciones coccidiales como uno de los posibles factores desencadenantes o predisponentes de la enterotoxemia. Estos resultados microbiológicos permitieron diseñar, preparar y mejorar una vacuna convencional inactivada que contiene, mayoritariamente, componentes bacterianos y exotoxinas A, Aβ2 y C aislados de casos fatales de la enfermedad. Desde su introducción en una empresa alpaquera del sur peruano en 2001, la vacuna ha logrado reducir progresivamente los índices de mortalidad por enterotoxemia de 19.5% (2000, sin vacuna) hasta alcanzar tasas menores al 5% en 2006

El contexto socioeconómico global y regional y sus efectos sobre la producción ganadera ( Articulo reseña, primera parte).

This review aims to bring to those involved in the processes of bovine production systems, and even consumers, our considerations on the necessary accurate assessment of the global and regional socio-economic context and its effects on livestock. Cattle farming has been depressed in its main bio-economic indicators, due to its dependence on supplements and agro-toxic, which must be used to avoid the growing deterioration of the system, which is influenced by the international socio-economic situation. The consequences of the crisis are reflected in global agriculture considering the necessary investments that provoke a demand for inputs to reach food and service productions that generate capital, so we see that this process is negatively affected, decreasing the diffusion of capital, which It causes disturbances in the primary producer-labor-agribusiness-market-consumers chain, within a wide range of commercial production systems. The current concern for the production of food of animal origin, in the opinion of many, is that it can be resolved by the introduction of cutting-edge agricultural technology, this constitutes a limited vision of the matter, creating dependencies on expensive resources. The problem can be solved with an improvement of the processes in the models of production systems, this is achieved, taking into account the global and regional socio-economic context of the systems, and the consequences that derive directly from their interpretation, which It will improve your organization and achieve greater efficiency. (246)Esta reseña tiene el objetivo de llevar a los implicados en los procesos de los sistemas de producción bovina, e incluso a los consumidores, nuestras consideraciones sobre la necesaria apreciación acertada del contexto socio-económico global y regional y sus efectos sobre la ganadería. La ganadería bovina se ha deprimido en sus principales indicadores bio-económicos, debido a su dependencia de suplementos y agro-tóxicos, que deben ser empleados para evitar el creciente deterioro del sistema, lo que está influído por la situación socio-económica internacional. Las consecuencias de la crisis se reflejan en la agricultura global considerando las necesarias inversiones que provocan una demanda de insumos para alcanzar producciones de alimentos y servicios que generan capital, así vemos que este proceso está afectado en forma negativa, disminuyendo la difusión del capital, que provoca perturbaciones en la cadena productor primario-mano de obra- agroindustria- mercado- consumidores, dentro de toda una amplia gama de sistemas de producción comercial. La preocupación actual por la producción de alimentos de origen animal, en criterio de muchos, es que la misma puede ser resuelta por la introducción de tecnología agrícola de punta, ello constituye una visión limitada del asunto, creando dependencias de recursos costosos. El problema puede solucionarse con una mejora de los procesos en los modelos de sistemas de producción, esto se logra, tomando en consideración el contexto socio-económico global y regional de los sistemas, y las consecuencias que de su interpretación se derivan directamente, lo cual permitirá mejorar su organización y alcanzar mayor eficiencia. (246

Phase I clinical trial in healthy adults of a nasal vaccine candidate containing recombinant hepatitis B surface and core antigens

SummaryBackgroundThe nasal vaccine candidate (NASVAC), comprising hepatitis B virus (HBV) surface (HBsAg) and core antigens (HBcAg), has been shown to be highly immunogenic in animal models.MethodsA phase I double-blinded, placebo-controlled randomized clinical trial was carried out in 19 healthy male adults with no serologic markers of immunity/infection to HBV. This study was aimed at exploring the safety and immunogenic profile of nasal co-administration of both HBV recombinant antigens. The trial was performed according to Good Clinical Practice guidelines. Participants ranged in age from 18 to 45 years and were randomly allocated to receive a mixture of 50μg HBsAg and 50μg HBcAg or 0.9% physiologic saline solution, as a placebo, via nasal spray in a five-dose schedule at 0, 7, 15, 30, and 60 days. A total volume of 0.5ml was administered in two dosages of 125μl per nostril. Adverse events were actively recorded 1h, 6h, 12h, 24h, 48h, 72h, 7 days and 30 days after each dose. Anti-HBs and anti-HBc titers were evaluated using corresponding ELISA kits at days 30 and 90.ResultsThe vaccine candidate was safe and well tolerated. Adverse reactions included sneezing (34.1%), rhinorrhea (12.2%), nasal stuffiness (9.8%), palate itching (9.8%), headache (9.8%), and general malaise (7.3%). These reactions were all self-limiting and mild in intensity. No severe or unexpected events were recorded during the trial. The vaccine elicited anti-HBc seroconversion in 100% of subjects as early as day 30 of the immunization schedule, while a seroprotective anti-HBs titer (≥10IU/l) was at a maximum at day 90 (75%). All subjects in the placebo group remained seronegative during the trial.ConclusionThe HBsAg–HBcAg vaccine candidate was safe, well tolerated and immunogenic in this phase I study in healthy adults. To our knowledge, this is the first demonstration of safety and immunogenicity for a nasal vaccine candidate comprising HBV antigens

Impacto del Centro de Estudios para el Desarrollo de la Producción Animal (CEDEPA) en la ganadería del territorio. 1. Programa de formación en extensión rural

The impact of a teaching program to train people as rural extension workers was evaluated at livestock centers in Camagüey province, Cuba, from 1996 to 2006. This project, named Rural Extension and Agricultural Technology Office (OFERTA), is and agricultural extension working tool developed by CEDEPA affiliated to the Faculty of Agricultural Sciences from Camagüey University. The highest impact of this program was centered on the project management and integration as well graduate and postgraduate teaching to train people as rural extension workers for regional livestock centers. Qualified personnel can be found at every production structure level; however, they are not always oriented towards the communication with simple producers, technology transfer, their own re-qualification, and the links and feedback with alike universities and research centers.Se evaluó el impacto de un programa de formación de recursos humanos como extensionistas, en el período de 1996 a 2006 en empresas ganaderas de Camagüey, Cuba. El proyecto se nombra Oficina de Extensión Rural y Tecnología Agropecuaria (OFERTA), dispositivo de trabajo en extensión agrícola creado en el Centro de Estudios para el Desarrollo de la Producción Animal (CEDEPA) de la Facultad de Ciencias Agropecuarias de la Universidad de Camagüey. Las áreas de mayor impacto del programa fueron la gestión-integración de proyectos y, por supuesto, la docencia de pre y posgrado para la formación de recursos humanos en extensión rural para las empresas ganaderas de la región. En las estructuras de producción hay personal calificado en cada frente, pero no siempre orientado al trabajo de comunicación con el productor de base, la transferencia de tecnología, su propia recalificación y el enlaceretroalimentación con las universidades y centros de investigación afines