Utilidad del ultrasonido transcraneal en Neurología y Neuropsiquiatría

Entre los sistemas dopaminérgicos que se modifican durante la evolución humana y que, en ciertas condiciones de conectividad y neurotransmisión anormal, desencadenan cambios patológicos en la adolescencia y adultez, se encuentra el mesolímbico basal. En adultos el ultrasonido transcraneal se realiza por la escama del hueso temporal con un equipamiento con transductor sectorial y focal de 1,8 a 2,8 MHz. Los puntos de evaluación ecográficos fundamentales son el mesencéfalo, el área de la sustancia negra, el rafe, el cuerpo estriado y los tálamos, el tercer ventrículo y los sectores orbitofrontales. A pesar del acceso anatómico limitado, es uno de los métodos de Neuroimágenes que cuantifica la ecogenicidad (de 0 a 3) y el área de sección de la sustancia negra (normal hasta 0,2 cm² ), lo cual se correlaciona con el empeoramiento de los síntomas motores parkinsonianos. Además, se evalúa y mensura el rafe (normal: 1 mm), que se correlaciona con el humor o la apatía según corresponda. Los otros hallazgos evaluables son los cambios en el espesor del tegmentum mesenfálico (ángulo interpeduncular menor o mayor de 60º), el aumento de la ecogenicidad de los tálamos y los cuerpos estriados, y la dilatación del tercer ventrículo (mayor de 5 mm). Su presencia colabora en el diagnóstico, clasificación, tratamiento y seguimiento de distintas patologías, como enfermedad de Parkinson, parálisis supranuclear progresiva, distonías, degeneración córtico-basal, esquizofrenia, depresiones, trastorno bipolar y autismo.

The basal mesolimbic system is among the dopaminergic systems that undergo changes during human evolution and that, under certain conditions, connectivity and abnormal neurotransmission trigger pathological changes during adolescence and adulthood. Transcranial ultrasound in adults is performed through the temporal squama with equipment that has a focal sectorial transducer from 1.8 to 2.8 MHz. The key points of the ultrasound evaluation are mesencephalon, substantia nigra area, raphe, striatum and thalamus, third ventricle, and orbitofrontal sectors. Despite its limited anatomical access, it is one of the neuroimaging methods that quantifies the echogenicity (0-3) and the sectional area of the substantia nigra (normal up to 0.2 cm²), which correlates with the worsening of Parkinsonian motor symptoms. It also evaluates and measures the raphe (normal 1 mm) which correlates with humour or apathy. Thickness changes of the mesencephalic tegmentum (interpeduncular angle, smaller or greater than 60º), thalamus and striatum increased echogenicity, and the third ventricle dilation (greater than 5 mm), are other possible findings. These are used to corroborate the diagnosis, classification, treatment and monitoring of different pathologies, like Parkinson's disease, supranuclear progressive palsy, dystonias, cortico-basal degeneration, schizophrenia, depression, bipolar disorder, and autism.

Basic fibroblast growth factor overexpression in endothelial cells: an autocrine mechanism for angiogenesis and angioproliferative diseases.

Basic fibroblast growth factor (bFGF) is expressed in vascular endothelium during tumor neovascularization and angioproliferative diseases. The ultimate significance of this observation is poorly understood. We have investigated the biological consequences of endothelial cell activation by endogenous bFGF in a mouse aortic endothelial cell line stably transfected with a retroviral expression vector harboring a human bFGF cDNA. Selected clones expressing M(r) 24,000, M(r) 22,000, and/or M(r) 18,000 bFGF isoforms were characterized by a transformed morphology and an increased saturation density. bFGF transfectants showed invasive behavior and sprouting activity in three-dimensional fibrin gels and formed a complex network of branching cord-like structures connecting foci of infiltrating cells when seeded on laminin-rich basement membrane matrix (Matrigel). The invasive and morphogenetic behavior was prevented by anti-bFGF antibody, revealing the autocrine modality of the process. The biological consequences of this autocrine activation were investigated in vivo. bFGF-transfected cells gave rise to highly vascularized lesions resembling Kaposi's sarcoma when injected in nude mice and induced angiogenesis in avascular rabbit cornea. When injected into the allantoic sac of the chick embryo, they caused an increase in vascular density and formation of hemangiomas in the chorioallantoic membrane. In conclusion, bFGF-overexpressing endothelial cells acquired an angiogenic phenotype and recruit quiescent endothelium originating angioproliferative lesions in vivo. These findings demonstrate that bFGF overexpression exerts an autocrine role for endothelial cells and support the notion that tumor neovascularization and angioproliferative diseases can be triggered by stimuli that induce vascular endothelium to produce its own autocrine factor(s).

Angiogenic phenotype induced by basic fibroblast growth factor transfection in brain microvascular endothelial cells.

Basic fibroblast growth factor (bFGF) is expressed in the vascular endothelium of human brain tumors. To investigate the biological consequences of a possible autocrine modality of microvascular endothelial cell activation by endogenous bFGF in these tumors, mouse brain microvascular endothelial cells were stably transfected with a retroviral expression vector harboring a human bFGF cDNA. When grown on tissue culture plastic, bFGF-transfected clones show a transformed morphology and increased saturation density. bFGF-transfectants have an invasive behavior when seeded on three-dimensional fibrin gel and originate endothelial cell sprouts when embedded within fibrin. Also, bFGF-transfected cells undergo morphogenetic organization and produce a complex network of branching cord-like structures connecting foci of infiltrating cells when seeded on Matrigel, a laminin-rich extracellular matrix material. In contrast, parental and mock-transfected cells do not invade fibrin gels nor organize on Matrigel. These findings demonstrate that bFGF overexpression induces an angiogenic phenotype in brain microvascular endothelial cells characterized by an invasive behavior and morphogenic potential. They support the notion that neovascularization of brain tumors can be triggered by stimuli that induce vascular endothelium to produce its own autocrine factor(s).

Immunocytochemical localization of plasminogen activators in carcinomas in the cervix and vulva.

The presence of plasminogen activators (PA) in a variety of solid tumours appears to correlate, in a number of instances, with enhanced invasive and/or metastatic ability. Urokinase and tissue-type plasminogen activators (u-PA and t-PA) in normal and neoplastic tissues of cervix and of vulva were immunohistochemically identified by means of polycyclonal antibodies. In addition, frozen sections were analysed for u-PA and t-PA activity by in-situ zymography technique. Data collected in our study showed that in invasive cancer u-PA increased more in malignant cells as compared to normal cells in both the inactive and active enzymatic forms. The t-PA distribution pattern was related to angiogenesis while it did not relate to the degree of tumor differentiation. A synergic interaction between proteolytic tumoral activity and proteolytic inflammatory action could be hypothesized.