Axonal regeneration in hippocampal and spinal cord organotypic slice cultures

Under normal conditions, axonal regeneration after lesions is not possible in mature CNS but can occur in embryonic and early postnatal nervous systems. In recent years, a number of possible strategies to enhance axonal regeneration and eventually treat spinal cord and brain injuries have been identified, some of which have been used successfully in animal experiments, but till now there is still no successful treatment available for patients. This problem is partly due to the complexity of the animal experiments which makes it difficult to compare different treatment strategies. In this project, we have used organotypic slice culture models to test the effectiveness of pharmacological compounds that interfere with various signal transduction mechanisms, to promote axonal regeneration. We used the entorhino hippocampal slice cultures to assess regeneration of entorhinal fibers projecting to the dentate gyrus after mechanical lesions and treatment. It was previously shown (Prang et. al., 2001) that there is a marked decrease in regenerating fibers when a lesion is made at 6 7 days in vitro or later in slices derived from postnatal day 5 6 mice. We took this as a control model where there is little spontaneous axonal regeneration, added treatments on the day of lesion and later traced for entorhinal axons with biotinylated dextran amine (BDA). In this study it was shown that compounds acting on the cAMP, PKC and G proteins can promote regeneration. Furthermore, we have identified the inhibition of the PI3 kinase pathway and the IP 3 receptor as potential drug targets that promote axonal regeneration. In order to study axonal growth in a spinal cord environment we have developed a spinal cord longitudinal organotypic slice culture model which allowed us to follow axons along the rostro caudal extension of the spinal cord. Slices of cervical spinal cord were cut in the sagittal plane from early postnatal mice and were maintained in culture for various time periods up to 4 weeks. Histological and immunohistochemical stainings of the cultures have shown that these slice cultures maintain the ventro dorsal polarity of the spinal cord and that an intrinsic fibre projection develops which runs along the rostro caudal extension of the spinal cord slice culture. After mechanical lesion, these fibres have the ability to regenerate spontaneously demonstrating the intrinsic ability of the spinal cord for repair, but this ability is decreased with increasing time in culture. During the culture period the axons became myelinated and expressed synaptic markers. These cultures could thus serve also as a model for myelin formation and synaptogenesis. We have analyzed the potential of axons from longitudinal spinal cord cultures to grow into an adjacent slice of cerebellar tissue. We could show that spinal cord axons do enter the cerebellar slice in particular when early postnatal spinal cord is combined with postnatal cerebellum. Pharmacological treatments were used to enhance axonal growth. Similarly to our findings in the entorhino hippocampal model, cAMP activators and PKC inhibitors promoted axonal growth from the spinal cord to the cerebellum. In cocultures of longitudinal spinal cord slices with cortical slices we have shown that fibers from the cortical slices grew extensively into the spinal cord slice and extended caudally for substantial distances. Our results demonstrate that organotypic slice cultures can be a useful tool to study axonal growth and regeneration. Intrinsic spinal cord axons have a considerable potential for spontaneous regeneration in the early postnatal period and are able to grow both through a mechanical lesion and into another tissue. Moreover, compounds interfering with signal transduction mechanisms, particularly cAMP, PKC, PI3 Kinase, G proteins and IP3 receptors, were able to promote axonal growth and regeneration in diverse slice culture models making them interesting drug candidates for the promotion of axonal regeneration

Pleomorphic sarcoma

67-year-old female who was referred from her general practitioner because of uncontrolled right popliteal knee pain which was very severe and continuously deteriorating. She could not bend her knee and sleep because of the pain. She could only walk on tiptoes with increased pain on weight bearing. Originally the popliteal swelling was thought to be a baker’s cyst. Arthroscopy showed no changes and MRI showed a large, primarily solid lesion in the popliteal fossa measuring 6x6x9 cms. This was biopsied and histopathology showed a sarcoma and an above knee amputation had to be performed. The patient is now well undergoing physiotherapy and occupational therapy to get back to her life.peer-reviewe

Network strategies for the new economy

In this paper we argue that the pace and scale of development in the information and communication technology industries (ICT) has had and continues to have major effects on the industry economics and competitive dynamics generally. We maintain that the size of changes in demand and supply conditions is forcing companies to make significant changes in the way they conceive and implement their strategies. We decompose the ICT industries into four levels, technology standards, supply chains, physical platforms, and consumer networks. The nature of these technologies and their cost characteristics coupled with higher degrees of knowledge specialisation is impelling companies to radical revisions of their attitudes towards cooperation and co-evolution with suppliers and customers. Where interdependencies between customers are particularly strong, we anticipate the possibility of winner-takes-all strategies. In these circumstances industry risks become very high and there will be significant consequences for competitive markets

¿Quo Vadis? Reclutamiento y Contratacion de Trabajadores Migrantes y su Acceso a la Seguridad Social: dinamicas de los sistemas de trabajo temporal migratorio en Norte y Centroamerica

Different regions and countries of the world face a serious need to design and make use of necessary policies and resources to better manage worker migration, thus ensuring the welfare and human rights of these people who, in the end, are of benefit to their society of origin, as well as the receiving society. Although international labor migration may turn out to be productive for many people, many of these migrant workers have unsatisfactory living and working conditions. While it is likely that their labor conditions are better than in their own country, in many cases they are inferior to the working conditions of nationals in their receiving country. Despite international standards to protect migrant workers, their labor rights are frequently abused, especially if they have immigrated in an irregular fashion. In this context, INEDIM took on the task of developing an integral and comprehensive document regarding different migrant worker and visa systems in Central and North America.The work presented here holds enormous value for delving in-depth to the forms of management of temporary migrant workers, as well as their access and guarantees to social and labor protection in North and Central America. This report addresses the problem of management of labor migrant flows among countries in our region. This study is based on an ordered and scrupulous methodology in which different migration systems and visa schemes for the hiring of temporary migrant workers are analyzed from the perspective of protection, respect for, guarantees and promotion of human rights. The study analyzes six systems that seek to regulate temporary migration in the region along the Central and North American corridor. The countries involved in these six systems are El Salvador, Guatemala, Mexico, Canada, the United States, Costa Rica and Nicaragua. The authors carry out a thorough and well-structured study based on two focuses of analysis: first, the processes for recruiting and contracting migrant workers and secondly, access to social protection for temporary migrant workers by means of the right to social security. From these two focuses, the authors are able to identify and demonstrate structural insufficiencies and gaps in the analyzed systems, which should guarantee labor security and social security for these workers

Darwinism, probability and complexity : market-based organizational transformation and change explained through the theories of evolution

The study of transformation and change is one of the most important areas of social science research. This paper synthesizes and critically reviews the emerging traditions in the study of change dynamics. Three mainstream theories of evolution are introduced to explain change: the Darwinian concept of survival of the fittest, the Probability model and the Complexity approach. The literature review provides a basis for development of research questions that search for a more comprehensive understanding of organizational change. The paper concludes by arguing for the development of a complementary research tradition, which combines an evolutionary and organizational analysis of transformation and change