Cyclic Nucleotide Phosphodiesterases and Compartmentation in Normal and Diseased Heart

International audienceCyclic nucleotide phosphodiesterases (PDEs) degrade the second messengers cAMP and cGMP, thereby regulating multiple aspects of cardiac function. This highly diverse class of enzymes encoded by 21 genes encompasses 11 families which are not only responsible for the termination of cyclic nucleotide signalling, but are also involved in the generation of dynamic microdomains of cAMP and cGMP controlling specific cell functions in response to various neurohormonal stimuli. In myocardium, the PDE3 and PDE4 families are predominant to degrade cAMP and thereby regulate cardiac excitation-contraction coupling. PDE3 inhibitors are positive inotropes and vasodilators in human, but their use is limited to acute heart failure and intermittent claudication. PDE5 is particularly important to degrade cGMP in vascular smooth muscle, and PDE5 inhibitors are used to treat erectile dysfunction and pulmonary hypertension. However, these drugs do not seem efficient in heart failure with preserved ejection fraction. There is experimental evidence that these PDEs as well as other PDE families including PDE1, PDE2 and PDE9 may play important roles in cardiac diseases such as hypertrophy and heart failure. After a brief presentation of the cyclic nucleotide pathways in cardiac cells and the major characteristics of the PDE superfamily, this chapter will present their role in cyclic nucleotide compartmentation and the current use of PDE inhibitors in cardiac diseases together with the recent research progresses that could lead to a better exploitation of the therapeutic potential of these enzymes in the future

Security Sector Reform After Armed Conflict

Security sector reform (SSR) is a central pillar of peace strategies, closely linked to but not interchangeable with state-building and democratization. There is a broad consensus that sustainable post-war peace needs a stable security environment and thus institutions that are able to inhibit non-legal manifestations of violence. The main elements of SSR are reforms in the state security institutions (military and police) as well as in the judiciary. The first generation SSR was characterized by Western blueprints and a lack of context sensitivity, with the empirical record being rather weak. As a consequence, programs moved away from “one size fits all” to a greater attention to local contexts. The need to include local, non-state actors has been acknowledged, but designing and implementing new approaches on the ground is neither easy nor going to happen in the immediate future. A further step in the evolvement of post-war SSR can be an approach to decolonize reform aspects: to radically question the origins of knowledge and practice of SSR and to center efforts more in the communities affected by reform than with ideals of the security sector that resemble more those in the Global North

Mental Health: A Focus on Stress, Coping, and Mental Illness as it Relates to Treatment Retention, Adherence, and Other Health Outcomes

Mental health problems are prevalent among HIV-infected individuals, with some estimates that 50% likely meet criteria for one or more psychiatric disorders. The mental health of HIV-infected individuals is important not only for quality-of-life concerns, but also in regard to HAART adherence and biological disease progression. The current review focuses on research published between 2009 and April of 2011, exploring mental health, coping, and stress in relation to HIV care behaviors including HAART adherence, quality of life, treatment retention, health care utilization, and disease progression amongst HIV-infected individuals. Specifically, we reviewed the most prevalent and interfering concerns among HIV-infected individuals—depression, post-traumatic stress disorder, interpersonal violence, stigma and shame, and body image concerns. Despite advances over the last 2 years documenting the deleterious effects of mental health on important HIV self-care behaviors, there is continued need for developing and disseminating evidence-based psychosocial interventions that integrate treating mental health problems with improving self-care behaviors for those living with HIV