Systemic delivery and activation of the TRAIL gene in lungs, with magnetic nanoparticles of chitosan controlled by an external magnetic field

Cynthia A Alvizo-Baez,1 Itza E Luna-Cruz,1 Natalia Vilches-Cisneros,2 Cristina Rodríguez-Padilla,1 Juan M Alcocer-González1 1Laboratory of Immunology and Virology, Biological Sciences Faculty, University Autonomous of Nuevo León, San Nicolás de los Garza, 2Pahologic Anatomy and Cytopathology Service of the University Hospital, University Autonomous of Nuevo León, Monterrey, Mexico Abstract: Recently, functional therapies targeting a specific organ without affecting normal tissues have been designed. The use of magnetic force to reach this goal is studied in this work. Previously, we demonstrated that nanocarriers based on magnetic nanoparticles could be directed and retained in the lungs, with their gene expression under the control of a promoter activated by a magnetic field. Magnetic nanoparticles containing the TRAIL gene and chitosan were constructed using the ionic gelation method as a nanosystem for magnetofection and were characterized by microscopy, ζ-potential, and retention analysis. Magnetofection in the mouse melanoma cell line B16F10 in vitro induced TRAIL-protein expression and was associated with morphological changes indicative of apoptosis. Systemic administration of the nanosystem in the tail vein of mice with melanoma B16F10 at the lungs produced a very significant increase in apoptosis in tumoral cells that correlated with the number of melanoma tumor foci observed in the lungs. The high levels of apoptosis detected in the lungs were partially related to mouse survival. The data presented demonstrate that the magnetofection nanosystem described here efficiently induces apoptosis and growth inhibition of melanoma B16F10 in the lungs. This new approach for systemic delivery and activation of a gene based in a nanocomplex offers a potential application in magnetic gene delivery for cancer. Keywords: magnetic nanoparticles, magnetofection, TRAIL, chitosan, apoptosi

Cefaléia no lupus eritematoso sistêmico: prevalência e condições associadas Headache and systemic lupus erythematosus: prevalence and associated conditions

OBJETIVO: Comparar a prevalência de cefaléia entre a população com lupus e normal e verificar as condições associadas à sua presença. MÉTODO: Analisaram-se 49 pacientes com lupus eritematoso (LES) e 50 controles quanto a episódios de cefaléia (enxaqueca e tensional). Em pacientes com LES estudou-se: presença de Raynaud, telangiectasias, vasculites cutâneas, convulsões e de anticorpos antifosfolípideos. RESULTADOS: Dos lúpicos com LES, 42 tinham cefaléia (85,7%), sendo 29 casos de enxaqueca e 13 tensional; no grupo controle, 28 tinham cefaléia (57,14%), sendo 18 com enxaqueca e 10 tensionais (p=0,0026 para enxaqueca). Nos pacientes com LES não se encontrou associação entre enxaqueca e Raynaud (p=0,34), telangiectasias (p=0,77), vasculites cutâneas (p=0,63) e convulsões (p=0,13). Também não se encontrou associação entre enxaqueca e anticorpos anticardiolipina Ig G (p=0,45), IgM (p=0,07) ou LAC (p=0,59). CONCLUSÃO: Enxaqueca é mais prevalente na população com L v ES. Este achado não está associado com Raynaud, telangiectasias, vasculites cutâneas, convulsões e anticorpos antifosfolípideos.<br>OBJECTIVE: To study the prevalence of headache in patients with systemic lupus erythematosus (SLE) and normal population as well as associated conditions. METHOD: Forty nine SLE patients and 50 controls were analyzed for presence of headaches (tensional and migraine). In the SLE group, we studied the occurrence of Raynaud, teleangiectasis, cutaneous vasculitis, convulsions and antiphospholipid antibodies. RESULTS: Among SLE patients, 42 had headaches (85.7%), 29 with migraine and 13 tensional; on the control group, 28 had headaches (57.1%), 18 migraine and 10 tension type with p=0.0026 for migraine. In SLE patients we did not find any association between migraine and Raynaud (p=0.34), teleangiectasis (p=0.77), cutaneous vasculitis (p=0.63), seizures (p=0.13), aCl IgG (p=0.45), IgM (=0.07) and LAC (p=0.59). CONCLUSION: Migraine is more prevalent in the SLE population. However, it has no relationship with Raynaud, teleangiectasis, seizures, cutaneous vasculitis and antiphospholipid antibodies

TAAR1 Modulates Cortical Glutamate NMDA Receptor Function

Trace Amine-Associated Receptor 1 (TAAR1) is a G protein-coupled receptor expressed in the mammalian brain and known to influence subcortical monoaminergic transmission. Monoamines, such as dopamine, also play an important role within the prefrontal cortex (PFC) circuitry, which is critically involved in high-o5rder cognitive processes. TAAR1-selective ligands have shown potential antipsychotic, antidepressant, and pro-cognitive effects in experimental animal models; however, it remains unclear whether TAAR1 can affect PFC-related processes and functions. In this study, we document a distinct pattern of expression of TAAR1 in the PFC, as well as altered subunit composition and deficient functionality of the glutamate N-methyl-D-aspartate (NMDA) receptors in the pyramidal neurons of layer V of PFC in mice lacking TAAR1. The dysregulated cortical glutamate transmission in TAAR1-KO mice was associated with aberrant behaviors in several tests, indicating a perseverative and impulsive phenotype of mutants. Conversely, pharmacological activation of TAAR1 with selective agonists reduced premature impulsive responses observed in the fixed-interval conditioning schedule in normal mice. Our study indicates that TAAR1 plays an important role in the modulation of NMDA receptor-mediated glutamate transmission in the PFC and related functions. Furthermore, these data suggest that the development of TAAR1-based drugs could provide a novel therapeutic approach for the treatment of disorders related to aberrant cortical functions