Objetivo
THE PROGRAMME WILL BE CONCERNED WITH INVESTIGATING THE RELATIONSHIP BETWEEN TISSUE PARENCHYMA AND VASCULAR ELEMENTS IN THE DEVELOPMENT OF LATE AND CHRONIC RADIATION DAMAGE FOLLOWING IRRADIATION WITH X-RAYS OR NEUTRONS. DIFFERENT ANIMAL STRAINS WILL BE USED WITH DIFFERING SENSITIVITY TO SEE IF THE RELATIONSHIP BETWEEN EARLY, LATE AND CHRONIC RADIATION DAMAGE ARE AFFECTED EQUALLY OR DIFFERENTIALLY. LOW DOSES OF FRACTIONATED RADIATIONS WILL BE INVESTIGATED USING THE TOPPING UP TECHNIQUE TO ESTABLISH WHETHER THERE IS A THRESHOLD DOSE/FRACTION BELOW WHICH NO FURTHER SPARING OF DAMAGE OCCURS BY INCREASING FRACTIONATION OF DOSE.
Relative biological effectiveness (RBE) measurements were made at low doses or fraction in the cervical cord with X-rays and neutrons of high and intermediate energy. Measurements were made of vascular permeability and these were used as markers of injury to the blood brain barrier. Also, attempts were made to reduce radiation injury to the central neurons systems (CNS) by the use of vasoactive drugs given postirradiation.
It was clear from the fractionation studies that the RBE for damage to the CNS at low doses per fraction was higher than for most other tissues. It was observed that the very high energy beam was also slightly less effective than at more moderate energies. These results emphasize the need to take great care when using fast neutrons to treat regions including the CNS.
Verapamyl, a calcium channel blocker, was used in an attempt to reduce permeability and hence oedema. It was not effective, possibly because it is the sodium channels which are opened by radiation injury and the damage is therefore unaffected by calcium channel blockers.
Dipyridamole, a muscle relaxant, was used to increase blood flow and thus reduce vessel blockage and transient ischaemia. It also reduces the thrombotic activity of the blood. This drug was effective in reducing the level of radiation damage.
Reperfusion injury is damage resulting from the production of superoxide radicals when previously ischaemic tissue is exposed to oxygen. Iron is a catalyst to the reaction. Desferrioxamine, a chelating agent, was given in combination with a low iron diet in order to decrease reperfusion injury. The low iron diet was necessary to reduce the replacement of free iron in tissue which was removed by the desferrioxamine. This drug combination was also effective. The result is also important in that it provides evidence that reperfusion injury may play a role in the development of radiation damage.
These studies demonstrate that it is possible to interfere with a ameliora te radiation damage by appropriate treatments postirradiation. The consequences for both radiation therapy and radiation protection could be considerable.
IN SPINAL CORD THE FIRST PHASE OF LATE DAMAGE PRODUCING SYMPTOMS OF ATAXIA AND PARALYSIS AT 3-7 MONTHS POST-IRRADIATION IS CURRENTLY ATTRIBUTED TO DAMAGE TO GLIAL ELEMENTS, THE OLIGODENDROCYTES, WHICH ARE CONCERNED WITH MYELINATION IN THE CNS. IT HAS BEEN SUGGESTED THAT FOCI OF DEMYLINATION DEVELOP INTO NECROSIS OF WHITE MATTER. HOWEVER THERE IS NO KNOWN NEURO-PATHOLOGICAL PATHWAY LEADING FROM DEMYLINATION TO NECROSIS. NECROSIS ATTRIBUTABLE TO NERVE DAMAGE ONLY FOLLOWS WALLERIAN DEGENERATION. IT HAS BEEN SUGGESTED THAT A TRANSIENT DEMYLINATION OCCURS AND INDEPENDENTLY SCATTERED WALLERIAN-TYPE DEGENERATION OF AXONS FROM ABOUT 2 WEEKS POST-IRRADIATION. IF AT THE SAME TIME THERE IS A TRANSIENT LOOSENING OF THE BLOOD BRAIN BARRIER DUE TO RELAXATION OF THE TIGHT JUNCTION BETWEEN CAPILLARY ENDOTHELIAL CELLS THIS MAY BE A SIGNIFICANT EVENT IN THE DEVELOPMENT OF NECROSIS. GLIAL ELEMENTS EG. ASTEROCYTES MAY BE INVOLVED IN THIS RELAXATION OF THE BLOOD BRAIN BARRIER.
IT IS PROPOSED TO INVESTIGATE THE DISRUPTION OF THE BLOOD BRAIN BARRIER USING DIFFERENT SIZED MOLECULES EG. ALPHA AMINO ISOBUTERIC ACID, WHICH IS ACTIVELY TRANSPORTED ACROSS THE BARRIER, AND BY THE PASSIVE LEAKAGE OF HORSE-RADISH PEROXIDASE WHICH CAN BE DETECTED HISTOCHEMICALLY. IF LEAKAGE CAN BE DETECTED IT MAY BE POSSIBLE TO DEVELOP TECHNIQUES USING RADIOLABELLED TRACERS (EG. INDIUM LABELLED EDTA) WHICH CAN BE DETECTED NON-INVASIVELY WITH A GAMMA CAMERA OR OTHERS WITH A POSITRON SCANNER. IT MAY ALSO BE POSSIBLE TO DETECT FLUORINE ALPHA AMINOBUTYRIC ACID LABELLED OR ATP CHANGES ASSOCIATED WITH ISCHEMIA WITH NMR SPECTOGRAPHY WHEN THIS BECOMES AVAILABLE.
THE DEVELOPMENT OF SYMPTOMS ARE DIFFERENT IN MOUSE AND RAT AND ANY DIFFERENCES IN VASCULAR LEAKAGE OR HISTOPATHOLOGY IN THE TWO SPECIES MAY GIVE SOME INSIGHT INTO MECHANISMS OF DAMAGE.
Ámbito científico (EuroSciVoc)
CORDIS clasifica los proyectos con EuroSciVoc, una taxonomía plurilingüe de ámbitos científicos, mediante un proceso semiautomático basado en técnicas de procesamiento del lenguaje natural. Véas: El vocabulario científico europeo..
CORDIS clasifica los proyectos con EuroSciVoc, una taxonomía plurilingüe de ámbitos científicos, mediante un proceso semiautomático basado en técnicas de procesamiento del lenguaje natural. Véas: El vocabulario científico europeo..
- ciencias naturales ciencias químicas química inorgánica metales alcalinos
- ciencias naturales ciencias químicas química inorgánica metales alcalinotérreos
- ciencias naturales ciencias químicas química inorgánica metales de postransición
- ciencias médicas y de la salud ciencias de la salud nutrición
- ciencias naturales ciencias químicas química inorgánica halógenos
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Programa(s)
Programas de financiación plurianuales que definen las prioridades de la UE en materia de investigación e innovación.
Programas de financiación plurianuales que definen las prioridades de la UE en materia de investigación e innovación.
Tema(s)
Las convocatorias de propuestas se dividen en temas. Un tema define una materia o área específica para la que los solicitantes pueden presentar propuestas. La descripción de un tema comprende su alcance específico y la repercusión prevista del proyecto financiado.
Datos no disponibles
Las convocatorias de propuestas se dividen en temas. Un tema define una materia o área específica para la que los solicitantes pueden presentar propuestas. La descripción de un tema comprende su alcance específico y la repercusión prevista del proyecto financiado.
Convocatoria de propuestas
Procedimiento para invitar a los solicitantes a presentar propuestas de proyectos con el objetivo de obtener financiación de la UE.
Datos no disponibles
Procedimiento para invitar a los solicitantes a presentar propuestas de proyectos con el objetivo de obtener financiación de la UE.
Régimen de financiación
Régimen de financiación (o «Tipo de acción») dentro de un programa con características comunes. Especifica: el alcance de lo que se financia; el porcentaje de reembolso; los criterios específicos de evaluación para optar a la financiación; y el uso de formas simplificadas de costes como los importes a tanto alzado.
Régimen de financiación (o «Tipo de acción») dentro de un programa con características comunes. Especifica: el alcance de lo que se financia; el porcentaje de reembolso; los criterios específicos de evaluación para optar a la financiación; y el uso de formas simplificadas de costes como los importes a tanto alzado.
Coordinador
W1N 4AL London
Reino Unido
Los costes totales en que ha incurrido esta organización para participar en el proyecto, incluidos los costes directos e indirectos. Este importe es un subconjunto del presupuesto total del proyecto.