Mitochondrial dysfunction and biogenesis: do ICU patients die from mitochondrial failure?

Mitochondrial functions include production of energy, activation of programmed cell death, and a number of cell specific tasks, e.g., cell signaling, control of Ca2+ metabolism, and synthesis of a number of important biomolecules. As proper mitochondrial function is critical for normal performance and survival of cells, mitochondrial dysfunction often leads to pathological conditions resulting in various human diseases. Recently mitochondrial dysfunction has been linked to multiple organ failure (MOF) often leading to the death of critical care patients. However, there are two main reasons why this insight did not generate an adequate resonance in clinical settings. First, most data regarding mitochondrial dysfunction in organs susceptible to failure in critical care diseases (liver, kidney, heart, lung, intestine, brain) were collected using animal models. Second, there is no clear therapeutic strategy how acquired mitochondrial dysfunction can be improved. Only the benefit of such therapies will confirm the critical role of mitochondrial dysfunction in clinical settings. Here we summarized data on mitochondrial dysfunction obtained in diverse experimental systems, which are related to conditions seen in intensive care unit (ICU) patients. Particular attention is given to mechanisms that cause cell death and organ dysfunction and to prospective therapeutic strategies, directed to recover mitochondrial function. Collectively the data discussed in this review suggest that appropriate diagnosis and specific treatment of mitochondrial dysfunction in ICU patients may significantly improve the clinical outcome

State Sovereignty, Popular Sovereignty and Individual Sovereignty: From Constitutional Nationalism to Multilevel Constitutionalism in International Economic Law?

This paper discusses the basic constitutional problem of modern international law since the UN Charter: How can the power-oriented international legal system based on “sovereign equality of states” be reconciled with the universal recognition of “inalienable” human rights deriving from respect for human dignity and popular sovereignty? State representatives, intergovernmental organizations, international judges and non-governmental organizations often express different views on how far the universal recognition of human rights has changed the subjects, structures, general principles, interpretative methods and “object and purpose” of international law (e.g. by the emergence of erga omnes obligations and jus cogens limiting state sovereignty to renounce human rights treaties, to refuse diplomatic protection of individuals abroad, or domestic implementation of international obligations for the benefit of domestic citizens). The paper explains why effective protection of human rights at home and abroad requires multilevel constitutional protection of individual rights as well as multilevel constitutional restraints of national, regional and worldwide governance powers and procedures. While all European states have accepted that the European Convention on Human Rights and EC law have evolved into international constitutional law, the prevailing paradigm for most states outside Europe remains “constitutional nationalism” rather than “multilevel constitutional pluralism.” Consequently, European proposals for reforms of international economic law often aim at “constitutional reforms” (e.g. of worldwide governance institutions) rather than only “administrative reforms”, as they are frequently favoured by non-European governments defending state sovereignty and popular sovereignty within a more power-oriented “international law among states.