BACKGROUND: As a step towards clinical use of AAV-mediated gene therapy, brains of large animals are used to settle delivery parameters as most brain connections, and relative sizes in large animals and primates, are reasonably common. Prior to application in the clinic, approaches that have shown to be successful in rodent models are tested in larger animal species, such as dogs, non-human primates, and in this case, minipigs. NEW METHOD: We evaluated alternate delivery routes to target the basal ganglia by injections into the more superficial corona radiata, and, deeper into the brain, the thalamus. Anatomically known connections can be used to predict the expression of the transgene following infusion of AAV5. For optimal control over delivery of the vector with regards to anatomical location in the brain and spread in the tissue, we have used magnetic resonance image-guided convection-enhanced diffusion delivery. RESULTS: While the transduction of the cortex was observed, only partial transduction of the basal ganglia was achieved via the corona radiata. Thalamic administration, on the other hand, resulted in widespread transduction from the midbrain to the frontal cortex COMPARISON WITH EXISTING METHODS: Compared to other methods, such as delivery directly to the striatum, thalamic injection may provide an alternative when for instance, injection into the basal ganglia directly is not feasible. CONCLUSIONS: The study results suggest that thalamic administration of AAV5 has significant potential for indications where the transduction of specific areas of the brain is required.

• Klíčová slova
• AAV, CED, CNS, Minipigs,
• MeSH
• Dependovirus genetika   MeSH
• genetická terapie metody   MeSH
• genetické vektory MeSH
• konvekce * MeSH
• magnetická rezonanční tomografie MeSH
• miniaturní prasata genetika   MeSH
• prasata MeSH
• psi MeSH
• thalamus * diagnostické zobrazování   MeSH
• zvířata MeSH
• Check Tag
• psi MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

We study effects of oscillatory convective flow in extracellular space on the velocity of chemical signal propagation having a form of a front wave above a cellular layer. We found that the time-averaged propagation velocity under oscillatory flow for a particular Péclet number amplitude is slower than the velocity under steady laminar flow regime for the same value of the Péclet number, but significantly faster than under no-flow conditions. We derive asymptotic values of the propagation velocity and asymptotic characteristics of the corresponding concentration fronts in high- and low-frequency regimes and show that the reason for the observed velocity increase under the oscillatory flow stems from a nonlinear dependence of the propagation velocity on the Péclet number, particularly from the convex character of the dependence. Our findings suggest that the specific responses of cellular cultures to different flow conditions in the extracellular space (for example, expression of atherosclerosis protective genes under steady laminar flow but not under oscillatory flow) is a consequence of a nonlinear coupling between the extracellular transport and complex intracellular reaction cascades forming a positive feedback loop of the autocrine signaling. This mechanism can operate independently of, or in conjunction with, a direct stress-sensing due to mechanotransduction.

• MeSH
• autokrinní signalizace * MeSH
• biologické modely * MeSH
• hydrodynamika * MeSH
• konvekce * MeSH
• lidé MeSH
• nelineární dynamika MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The paper presents the results of the mathematical modelling the effects of hypogravity on the heat output by the spontaneous convection. The theoretical considerations were completed by the experiments "HEAT EXCHANGE 1" performed on the biosatellite "KOSMOS 936". In the second experiment "HEAT EXCHANGE 2" accomplished on the board of the space laboratory "SALYUT 6" was studied the effect of the microgravity on the thermal state of a man during the space flight. Direct measurement in weightlessness prowed the capacity of the developed electric dynamic katathermometer to check directly the effect of the microgravity on the heat output by the spontaneous convection. The role of the heat partition impairment's in man as by the microgravity, so by the inadequate forced convection are clearly expressed in changes of the skin temperature and the subjective feeling of the cosmonaut's thermal comfort. The experimental extension of the elaborated methods for the flexible adjustment of the thermal environment to the actual physiological needs of man and suggestions for the further investigation are outlined.

• MeSH
• konvekce MeSH
• kosmický let * MeSH
• lidé MeSH
• noha (od hlezna dolů) fyziologie   MeSH
• stav beztíže škodlivé účinky   MeSH
• teoretické modely MeSH
• teplota kůže fyziologie   MeSH
• termodynamika * MeSH
• termoregulace fyziologie   MeSH
• vysoká teplota MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

The spontaneous streaming of air around surfaces of warm bodies conditioned by gravitation is missing in the weightless condition. This implies a change in the thickness of the surface air layer and its interference with the heat output of an organism. The paper describes the use of an electric dynamic katathermometer (EDK) for automatic and continuous scanning of heat output and presents results of measuring basic characteristics of the surface layer under defined laboratory conditions, and their relation to heat output.

• MeSH
• konvekce MeSH
• kosmický let MeSH
• lidé MeSH
• pohyb vzduchu * MeSH
• reprodukovatelnost výsledků MeSH
• stav beztíže * MeSH
• teploměry MeSH
• termoregulace fyziologie   MeSH
• vítr MeSH
• vysoká teplota * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH