The thesis of this review is that oxidative stress is the central factor in major depressive disorder (MDD) and Alzheimer’s disease (AD). The major elements involved are inflammatory cytokines, the hypothalamic pituitary axis, the hypothalamic pituitary gonadal, and arginine vasopressin systems, which induce glucocorticoid and “oxidopamatergic” cascades when triggered by psychosocial stress, severe life threatening events, and mental-affective and somatic diseases. In individuals with a genomic vulnerability to depression these cascades may result in chronic depression-anxiety-stress spectra, resulting in MDD and other known depressive syndromes. In contrast, in subjects with genomic vulnerability to Alzheimer’s disease, oxidative stress-induced brain damage triggers specific antioxidant defenses, i.e. increased levels of amyloid-β (Aβ) and aggregation of hyper-phosphorylated tau, resulting in paired helical filaments and impaired functions related to the ApoEε4 isoform, leading to complex pathological cascades culminating in AD. Surprisingly, all the AD associated molecular pathways mentioned in this review have been shown to be similar or analogous to those found in depression, including structural damage, i.e. hippocampal and frontal cortex atrophy. Other interacting molecular signals, i.e. GSK-3β, convergent survival factors (brain-derived neurotrophic factor and heat shock proteins), and transition-redox metals are also mentioned to emphasize the vast array of intermediates that could interact via comparable mechanisms in both MDD and AD.

Respostas estatísticas dos parâmetros funcionais são largamente utilizadas após administração de broncodilatador (Bd) nos laboratórios de função pulmonar em doenças com obstrução ao fluxo aéreo. Sua relevância clínica é discutível. Objetivo: Determinar que parâmetros espirométricos refletem a melhora na tolerância ao exercício e na dispnéia em resposta a broncodilatador em doenças pulmonares obstrutivas. Métodos: 50 pacientes com DPOC e/ou asma (VEF 1 /CVF = 41 ± 11%) realizaram manobras de CV lenta e forçada, VVM e um teste de caminhada em corredor de seis minutos após treinamento, antes e após salbutamol, 400mcg fornecido por spray com espaçador. As respostas a broncodilatador foram expressas em valores absolutos, como incremento em relação ao valor inicial e em relação aos valores previstos. Resposta após Bd foi considerada clinicamente significante quando a distância percorrida se elevou 30m ou mais e/ou a dispnéia foi reduzida dois ou mais pontos com qualquer aumento na caminhada. Resultados: 32 pacientes foram considerados respondedores (R) e 18 não respondedores (NR). Como a distância caminhada em seis minutos se correlacionou com a idade (rs = -0,38; p < 0,01), análise dos dados espirométricos foi realizada incluindo a idade como covariada e expressa como x ± EPE. O incremento do VEF 1 não diferiu nos dois grupos: R = 255 ± 57ml, NR = 256 ± 43ml. Idem para a VVM: R = 11 ± 2L/min, NR = 10 ± 2L/min.A melhor separação (p < 0,01) foi dada pela mudança da capacidade inspiratória (CI) seguida da mudança da capacidade vital lenta (CV): CI% da inicial nos R = 23 ± 3% e os NR = 3 ± 4%; CI absoluta: R = 411 ± 58ml, NR = 163 ± 77ml; CI% previsto: R = 19 ± 3% e NR = 3 ± 4%. Para a CV os valores observados foram: CV% do inicial -R = 18 ± 2% e NR = 9 ± 3%; CV absoluta -R = 448 ± 52ml e NR = 256 ± 70ml. Incrementos para a CI > 15% do inicial e 0,3L e da CV > 15% da inicial e 0,4L separaram os respondedores com valor preditivo positivo (VPP) em torno de 90%. Conclusão: A melhora do VEF 1 , CVF e VVM não prediz melhora na capacidade de exercício após Bd. Esta é melhor refletida por aumentos na CI e/ou CV Recebido para publicação em 7/4/00. Aprovado, após revisão, em 24/10/00.

No abstract

Alzheimer’s disease (AD) exhibits a complex etiology that simultaneously manifests as a complex cellular, neurobiological, molecular, anatomic–physiological and clinical entity. Other significant psychiatric conditions, such as depression and schizophrenia, may also present with complex and concurrent clinical and/or molecular phenotypes. These neuropsychiatric pathologies also originate from both environmental and genetic factors. We analyzed the molecular phenotypes of AD and discuss them with respect to the classical theories, which we integrated into mechanisms that share molecular and/or anatomical connections. Based on these mechanisms, we propose an interaction model and discuss the model in light of studies that refute or support it. Given the spectrum of AD phenotypes, we limit the scope of our discussion to a few, which facilitates concrete analysis. In addition, the study of specific, individual pathogenic phenotypes may be critical to defining the complex mechanisms leading to AD, thereby improving strategies for developing novel therapies.

System self-integration from open sets of components provides the basis for open adaptability to unpredictable environments. Hierarchical architectures are essential for enabling such systems to scale, as they allow to compromise between processing detailed knowledge in parallel and coordinating parallel processes from a more abstract viewpoint; recursively. This position paper aims to bring to the fore the following key design aspect of such hierarchical systems: how should the authority of decision / action be assigned across hierarchical levels, with respect to the self-awareness capabilities of these levels? The difficulty lays in that all levels lack knowledge, which may be key to certain decisions, because lower levels have detailed knowledge but within a narrow scope (good for local customisation), and higher levels have a broader scope but no details (good for global coordination). We highlight the most obvious authority schemes available and discuss their advantages and shortcomings: top-down, bottom-up, and iterative (yoyo). We discuss three detailed application examples from our previous work on hierarchical systems, pointing-out the knowledge and authority schemes employed and the possible alternatives. This provides a basis for offering system designers the necessary understanding and tools for taking the appropriate decisions with respect to the distribution of self-awareness capabilities and authority of decision / action across hierarchical system levels.