The sporadic nature of Alzheimer's disease argues for an environmental link that may drive AD pathogenesis; however, the triggering factors and the period of their action are unknown. Recent studies in rodents have shown that exposure to lead during brain development predetermined the expression and regulation of the amyloid precursor protein and its amyloidogenic beta-amyloid product in old age. Here, we report that the expression of AD-related genes [APP, BACE1 ] as well as their transcriptional regulator were elevated in aged (...) monkeys exposed to Pb as infants. Furthermore, developmental exposure to Pb altered the levels, characteristics, and intracellular distribution of Abeta staining and amyloid plaques in the frontal association cortex. These latent effects were accompanied by a decrease in DNA methyltransferase activity and higher levels of oxidative damage to DNA, indicating that epigenetic imprinting in early life influenced the expression of AD-related genes and promoted DNA damage and pathogenesis. These data suggest that AD pathogenesis is influenced by early life exposures and argue for both an environmental trigger and a developmental origin of AD. (shrink)

Oxidative damage to DNA has been associated with neurodegenerative diseases. Developmental exposure to lead has been shown to elevate the Alzheimer's disease related beta-amyloid peptide , which is known to generate reactive oxygen species in the aging brain. This study measures the lifetime cerebral 8-hydroxy-2'-deoxyguanosine levels and the activity of the DNA repair enzyme 8-oxoguanine DNA glycosylase in rats developmentally exposed to Pb. Oxo8dG was transiently modulated early in life , but was later elevated 20 months after exposure to Pb (...) had ceased, while Ogg1 activity was not altered. Furthermore, an age-dependent loss in the inverse correlation between Ogg1 activity and oxo8dG accumulation was observed. The effect of Pb on oxo8dG levels did not occur if animals were exposed to Pb in old age. These increases in DNA damage occurred in the absence of any Pb-induced changes in copper/zinc-superoxide dismutase , manganese-SOD , and reduced-form glutathion . These data suggest that oxidative damage and neurodegeneration in the aging brain could be impacted by the developmental disturbances. (shrink)

I have argued in other work that emotion, attentional functions, and executive functions are three interpenetrant global state variables, essentially differential slices of the consciousness pie. This paper will outline the columnar architecture and connectivities of the PAG (periaqueductal gray), its role in organizing prototype states of emotion, and the re-entry of PAG with the extended reticular thalamic activating system (“ERTAS”). At the end we will outline some potential implications of these connectivities for possible functional correlates of PAG networks that (...) are just starting to be mapped. Overall, we will look at many lines of evidence that PAG should be conceptualized as a peri-reticular structure that has a foundational role in emotion, in generating the meaningful organization of behavior by the brain through prototype emotional states, and in allowing the various emotional systems to globally influence and tune both the forebrain and brainstem. Finally, we address implications of these concepts for what is currently understood about consciousness, underlining the need for somewhat more humility within consciousness studies about our current level of understanding of consciousness in the brain, combined with a deeper appreciation of the intrinsic connections between emotion and consciousness. One hopes that more concerted empirical interest in structures underneath the thalamus, combined with a deeper appreciation for the fundamental role that organismic and social value must have in bootstrapping awareness in the developing brain, would begin more widely to influence the fundamental lines of neuroscientific research in both emotion studies and consciousness studies. (shrink)

The four principles approach to biomedical ethics (4PBE) has, since the 1970s, been increasingly developed as a universal bioethics method. Despite its wide acceptance and popularity, the 4PBE has received many challenges to its cross-cultural plausibility. This paper first specifies the principles and characteristics of ancient Chinese medical ethics (ACME), then makes a comparison between ACME and the 4PBE with a view to testing out the 4PBE's cross-cultural plausibility when applied to one particular but very extensive and prominent cultural context. (...) The result shows that the concepts of respect for autonomy, non-maleficence, beneficence and justice are clearly identifiable in ACME. Yet, being influenced by certain socio-cultural factors, those applying the 4PBE in Chinese society may tend to adopt a "beneficence-oriented", rather than an "autonomy-oriented" approach, which, in general, is dissimilar to the practice of contemporary Western bioethics, where "autonomy often triumphs". (shrink)

Filosofische beschouwingen over de ontwikkeling van het volkenrechtelijke begrip mensenrechten.

Children, because of age-related reasons, are a vulnerable population, and protecting their health is a social, scientific and emotional priority. The increased susceptibility of children and fetuses to environmental agents has been widely discussed by the scientific community. Children may experience different levels of chemical exposure than adults, and their sensitivity to chemical toxicities may be increased or decreased in comparison with adults. Such considerations also apply to unborn and newborn children. Therefore, research on children is necessary in both clinical (...) and environmental fields, to provide age-specific relevant data regarding the efficacy and safety of medical treatments, and regarding the assessment of risk from unintended environmental exposure. In this context, the stakeholders are many, including children and their parents, physicians and public health researchers, and the society as a whole, with its ethical, regulatory, administrative and political components. The important ethical issues are information of participants and consent to participate. Follow-up and protection of data should be discussed in the context of biobanks, where children obtain individual rights when they become adults. It is important to realise that there are highly variable practices within European countries, which may have, in the past, led to differences in practical aspects of research in children. A number of recommendations are provided for research with children and environmental health. Environmental research with children should be scientifically justified, with sound research questions and valid study protocols of sufficient statistical power, ensuring the autonomy of the child and his/her family at the time of the study and later in life, if data and samples are used for follow-up studies. When children are enrolled, we recommend a consent dyad, including parental informed consent and the child’s assent and/or informed consent from older minors. For evaluation of the studies including children, a paediatrician should always be involved in the research ethics committee. (shrink)

This paper examines whether the modern bioethical principles of respect for autonomy, beneficence, non-maleficence, and justice proposed by Beauchamp and Childress are existent in, compatible with, or acceptable to the leading Chinese moral philosophy—the ethics of Confucius. The author concludes that the moral values which the four prima facie principles uphold are expressly identifiable in Confucius’ teachings. However, Confucius’ emphasis on the filial piety, family values, the “love of gradation”, altruism of people, and the “role specified relation oriented ethics” will (...) inevitably influence the “specification” and application of these bioethical principles and hence tend to grant “beneficence” a favourable position that diminishes the respect for individual rights and autonomy. In contrast, the centrality of respect for autonomy and its stance of “first among equals” are more and more stressed in Western liberal viewpoints. Nevertheless, if the Confucian “doctrine of Mean” and a balanced “two dimensional personhood” approach are properly employed, this will require both theorists and clinicians, who are facing medical ethical dilemmas, of searching to attain due mean out of competing moral principles thus preventing “giving beneficence a priority” or “asserting autonomy must triumph”. (shrink)