[Non invasive gene therapy in neurological diseases]. / Terapia genica no invasiva en enfermedades neurologicas.

INTRODUCTION: Brain gene therapy consists of introducing nucleic acids into nerve tissue whose expression may prove to be therapeutically useful. This genetic material is indirectly introduced by means of non invasive gene therapy into the blood thereby avoiding its direct injection into the brain and the damage to the blood brain barrier. AIM: The different non invasive vectors and means of gene transfer to the central nervous system will be discussed. DEVELOPMENT: There has been a remarkable breakthrough in recent years in non invasive gene transfer strategies into the central nervous system. The development of new serotypes of adenoassociated vectors, such as AAV9, and of functionalized nanoparticles, such as pegylated immunoliposomes, polymeric nanoparticles, pegylated nanoparticles, dendrimers, fullerens, as well as specific transporters specific to the low density lipoprotein receptor family, means that it is now possible to introduce and express gene material in nerve tissue following peripherical administration of the above mentioned vectors. CONCLUSIONS: Non invasive gene therapy entails exciting new perspectives for the treatment of the numerous neurological diseases for which there are no effective pharmacological treatments. Studies already performed on animals have proved to be highly promising and it is likely that, in the next few years, they will give rise to non invasive gene therapy procedures which will be useful and safe for treating patients.

Inverse association between serum resistin and insulin resistance in humans.

AIM: To determine how serum concentrations of resistin are distributed in humans in relation to insulin resistance, type 2 diabetes, and obesity. METHODS: Cross-sectional, descriptive study carried out in a random sample (n=713, 43% men, 18-75 years) of general population of inhabitants of the Canary Islands (Spain). Serum resistin concentration, HOMA2-IR, anthropometric parameters, drug consumption and physical activity were recorded. RESULTS: There were no differences in resistin concentration between participants with and without diabetes (3.1+/-0.2 vs. 3.2+/-0.1ng/mL; p=0.566), or between obese and non-obese participants (3.1+/-0.1 vs. 3.2+/-0.1ng/mL; p=0.803). Individuals with abdominal obesity (waist-hip ratio [WHR] >or=1 in men or >or=0.9 in women) had lower concentrations of resistin (3.0+/-0.13 vs. 3.4+/-0.1ng/mL; p<0.001). The correlations between resistin and HOMA2-IR (r=-0.231; p<0.001) and between resistin and WHR (r=-0.202; p<0.001) were inverse. Multivariate analysis corroborated the inverse association of this cytokine with HOMA2-IR, WHR and, in women, also retained in the model the direct association between resistin and physical activity and the inverse association between resistin and antihypertensive agents. CONCLUSIONS: In this population resistin is inversely associated with insulin resistance and abdominal obesity.

Reelin-immunoreactive neurons in the adult vertebrate pallium.

Reelin, an extracellular matrix protein, plays a crucial role in cortical development. By using Reelin-immunohistochemistry in different vertebrates (fish, amphibians, reptiles, and mammals : insectivores, odontocetes, rodents, carnivores and man) we show here that Reelin is also expressed by a variety of neurons in the adult pallium. In the everted telencephalon of the zebrafish, Reelin-positive neurons are widely distributed over the dorsal pallium. In land vertebrates, the most consistent and evolutionary conserved location of Reelin-expressing neurons is in the cell-sparse molecular layer associated with laminated cortical organization. We describe an additional heterogeneous population of Reelin-positive neurons outside the molecular layer, the location and distribution of which are more variable, and which may reflect major evolutionary changes in cortical architecture. In squamate reptiles, the Reelin-negative main cell layer is flanked by a superficial and a deep plexiform layer which both contain Reelin-expressing neurons. In mammals, Reelin-positive interneurons are dispersed throughout layers II--VI; the human neocortex is particularly poor in Reelin-positive interneurons. Reelin is also expressed by large stellate and modified pyramidal neurons in layer II of the mammalian entorhinal cortex, and in the superficial lateral cortex of lizards. Examination of this cell population (layer II Pre-alpha) in human brains of different age groups points to a decrease in Reelin-expression in the course of adult life.