Down-regulation of the cardiac sarcoplasmic reticulum ryanodine channel in severely food-restricted rats

We have shown that myocardial dysfunction induced by food restriction is related to calcium handling. Although cardiac function is depressed in food-restricted animals, there is limited information about the molecular mechanisms that lead to this abnormality. The present study evaluated the effects of food restriction on calcium cycling, focusing on sarcoplasmic Ca2+-ATPase (SERCA2), phospholamban (PLB), and ryanodine channel (RYR2) mRNA expressions in rat myocardium. Male Wistar-Kyoto rats, 60 days old, were submitted to ad libitum feeding (control rats) or 50% diet restriction for 90 days. The levels of left ventricle SERCA2, PLB, and RYR2 were measured using semi-quantitative RT-PCR. Body and ventricular weights were reduced in 50% food-restricted animals. RYR2 mRNA was significantly decreased in the left ventricle of the food-restricted group (control = 5.92 ± 0.48 vs food-restricted group = 4.84 ± 0.33, P < 0.01). The levels of SERCA2 and PLB mRNA were similar between groups (control = 8.38 ± 0.44 vs food-restricted group = 7.96 ± 0.45, and control = 1.52 ± 0.06 vs food-restricted group = 1.53 ± 0.10, respectively). Down-regulation of RYR2 mRNA expressions suggests that chronic food restriction promotes abnormalities in sarcoplasmic reticulum Ca2+ release.

Lack of evidence for regulation of cardiac P-type ATPases and MAP kinases in transgenic mice with cardiac-specific overexpression of constitutively active α1B-adrenoceptors

The regulatory function of α1B-adrenoceptors in mammalian heart homeostasis is controversial. The objective of the present study was to characterize the expression/activity of key proteins implicated in cardiac calcium handling (Na+/K+-ATPase and Ca2+-ATPases) and growth (ERK1/2, JNK1/2 and p38) in mice with cardiac-selective overexpression of constitutively active mutant α1B-adrenoceptor (CAMα1B-AR), which present a mild cardiac hypertrophy phenotype. Immunoblot assays showed that myocardial plasma membrane Ca2+-ATPase (PMCA) expression was increased by 30% in CAMα1B-AR mice (N = 6, P < 0.05), although there was no change in sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2) expression. Moreover, total Ca2+-ATPase activity was not modified, but a significant increase in the activity of the thapsigargin-resistant (PMCA) to thapsigargin-sensitive (SERCA) ratio was detected. Neither Na+/K+-ATPase activity nor the expression of α1 and α2 subunit isoforms was changed in CAMα1B-AR mouse hearts. Moreover, immunoblot assays did not provide evidence for an enhanced activation of the three mitogen-activated protein kinases studied in this stage of hypertrophy. Therefore, these findings indicate that chronic cardiac α1B-AR activation in vivo led to mild hypertrophy devoid of significant signs of adaptive modifications concerning primary intracellular calcium control and growth-related proteins, suggesting a minor pathophysiological role of this adrenergic receptor in mouse heart at this stage of development.

The Social Power of Bodin's 'Sovereignty' and International Law

The word ‘sovereignty’ provides a forceful example of the social power of language as an organic instrument playing a leading role in the continuous and continuing process of creating and transforming human reality. The paper examines a pivotal episode in the history of the word ‘sovereignty’ — its formal introduction in the 16th century by Jean Bodin in his Six Livres de la Republique. It focuses on the social effects ‘sovereignty’ has had on the shared consciousness of humanity, including that of the international community. The proposed metalogical inquiry adopts a method that draws from the hermeneutic school of historical knowledge. The argument is that Bodin used ‘sovereignty’ for the purpose of attributing to the ruler (the French king) supreme power in the hierarchical organisational structure of society. This idea of a pyramid of authority is found in different elements of the discourse in Six Livres de la Republique, which is examined in the immediate context of Bodin’s personal background as well as the extended social, political and intellectual context of 16th century France. The conclusion shows that Bodin’s work was the first seminal step in the development of contemporary ideas of ‘internal sovereignty’ and ‘external sovereignty’. It is thus part of the history of the true power that the word at hand has exercised in framing the international state system and hence the international legal system.

National Application of International Law: The Statutory Interpretation Perspective

Reprinted with permission of the Publisher from The Canadian Yearbook of Internation Law, 41 by Don McRae © University of British Columbia Press 2003. All rights reserved.