Towards a unified theory of health-disease: II. Holopathogenesis

Este trabalho apresenta uma abordagem sistemática para a modelagem de várias classes de enfermidade-moléstia-doença, designada como Holopatogênese. Holopatogênese é definido como um processo de sobre determinação de doenças e condições relacionadas, tomadas como um integral, compreendendo facetas selecionadas da saúde enquanto objeto complexo. Em primeiro lugar, o marco conceitual da Holopatogênese é apresentado como uma série de três interfaces significativas: biomolecular- imunológica, fisiopatológico-clínica e epidemiológico-ecossocial. Em segundo lugar, proposições derivadas da Holopatogênese são introduzidas a fim de permitir o desenho do complexo doença-enfermidade como uma rede hierárquica de redes. Em terceiro lugar, propõe-se uma formalização de correspondências intra e inter nível, processos de sobredeterminação, efeitos e laços componentes da Holopatogênese. Finalmente, o modelo Holopatogênese é avaliado como uma patologia teórica compreensiva tomada como passo preliminar para uma teoria unificada de saúde-doença

Thalamic projections of the fusiform gyrus in man.

Previous retrograde degeneration studies have shown that human extrastriate visual cortex receives projections from the pulvinar, but their precise topographical organization remained unknown. We report on the distribution of thalamic projections originating in the fusiform gyrus, as studied with the Nauta method for anterogradely degenerating axons, in a case of right fusiform gyrus infarction. Ipsilaterally to the lesion, high density of afferents was found in the inferior pulvinar nucleus and a low density in the medial pulvinar nucleus as well as in the postero-inferior part of the reticular nucleus; no degenerating fibres were found in the lateral geniculate body. Degenerating axons were completely absent in the contralateral thalamus. Thus, there is a precise topographic relationship between parts of the extrastriate cortex and the pulvinar, suggesting segregated thalamocortical pathways for different parts of the extrastriate cortex. As in nonhuman primates, the human inferior temporal cortex has no direct output to the lateral geniculate body

Direct and astrocyte-mediated effects of ethanol on brain-derived endothelial cells

The effects of ethanol have been studied in the central nervous system, however there exists only scarce information about the effects of ethanol on endothelial cells forming the blood-brain barrier. As some properties of brain endothelial cells are modulated by underlying astrocytes, the effect of ethanol on cerebral microvasculature might be indirect and mediated by astrocytes. To analyse this question, we added to rat brain-derived endothelial cells (rbEC) in culture either only ethanol (0, 15 and 150 mM) or ethanol conjointly with soluble factors secreted by astrocytes. Alternatively, astrocytes were exposed to ethanol and the medium was added to rbEC. The effects of treatments were evaluated on cell growth and expression of specific proteolytic markers of rbEC. The experiments showed that while the addition of ethanol alone to rbEC increased the expression of gamma-glutamyltranspeptidase and cell growth following an initial toxic effect, the most significant effects were seen when ethanol was added to rbEC together with astrocytic factors or when medium conditioned by astrocytes exposed to ethanol was added to rbEC. In particular, the expression of angiotensin converting enzyme in endothelial cells was dose-dependently increased. These results indicate that the hypertensive and toxic effects of ethanol are mediated by ethanol and soluble factor(s) secreted by astrocytes and dependent on the expression of angiotensin converting enzyme in the brain endothelium. Thus, when evaluating in vitro the effects of toxic substances such as ethanol on the cerebral endothelium, the modulating effect of cells surrounding cerebral vessels must be accounted fo