The Moral Duty of Self-Preservation

UIDB/00183/2020 UIDP/00183/2020This chapter provides an in-depth examination of Kant’s view of suicide. After a contextualization of Kant’s prohibition of suicide (§2.1), seven different arguments against the moral permissibility of suicide are identified: three from the Lectures on Ethics (§2.2) and four from the published writings (§2.3). Each argument is presented (with possible variations) and explained. Strengths and flaws are pointed out, and possible objections and counter-objections are discussed, taking into consideration the abundant bibliography on the subject. The conclusion is that, against a recent trend in secondary literature, which tends to read Kant as justifying not only a right, but even a duty to suicide, Kant does not allow for any exception to his strict prohibition of suicide.authorsversionpublishe

Membrane Potential Controls Adipogenic and Osteogenic Differentiation of Mesenchymal Stem Cells

Background: Control of stem cell behavior is a crucial aspect of developmental biology and regenerative medicine. While the functional role of electrophysiology in stem cell biology is poorly understood, it has become clear that endogenous ion flows represent a powerful set of signals by means of which cell proliferation, differentiation, and migration can be controlled in regeneration and embryonic morphogenesis. Methodology/Principal Findings: We examined the membrane potential (Vmem) changes exhibited by human mesenchymal stem cells (hMSCs) undergoing adipogenic (AD) and osteogenic (OS) differentiation, and uncovered a characteristic hyperpolarization of differentiated cells versus undifferentiated cells. Reversal of the progressive polarization via pharmacological modulation of transmembrane potential revealed that depolarization of hMSCs prevents differentiation. In contrast, treatment with hyperpolarizing reagents upregulated osteogenic markers. Conclusions/Significance: Taken together, these data suggest that the endogenous hyperpolarization is a functiona

Ion channel pharmacology

Because ion channels are involved in many cellular processes, drugs acting on ion channels have long been used for the treatment of many diseases, especially those affecting electrically excitable tissues. The present review discusses the pharmacology of voltage-gated and neurotransmitter-gated ion channels involved in neurologic diseases, with emphasis on neurologic channelopathies. With the discovery of ion channelopathies, the therapeutic value of many basic drugs targeting ion channels has been confirmed. The understanding of the genotype–phenotype relationship has highlighted possible action mechanisms of other empirically used drugs. Moreover, other ion channels have been pinpointed as potential new drug targets. With regards to therapy of channelopathies, experimental investigations of the intimate drug– channel interactions have demonstrated that channel mutations can either increase or decrease affinity for the drug, modifying its potential therapeutic effect. Together with the discovery of channel gene polymorphisms that may affect drug pharmacodynamics, these findings highlight the need for pharmacogenetic research to allow identification of drugs with more specific effects on channel isoforms or mutants, to increase efficacy and reduce side effects. With a greater understanding of channel genetics, structure, and function, together with the identification of novel primary and secondary channelopathies, the number of ion channel drugs for neurologic channelopathies will increase substantially