Evolving Strategies for Use of Phytochemicals in Prevention and Long-Term Management of Cardiovascular Diseases (CVD).

This report describes major pathomechanisms of disease in which the dysregulation of host inflammatory processes is a major factor, with cardiovascular disease (CVD) as a primary model, and reviews strategies for countermeasures based on synergistic interaction between various agents, including drugs and generally regarded as safe (GRAS) natural medical material (NMM), such as Ginkgo biloba, spice phytochemicals, and fruit seed flavonoids. The 15 well-defined CVD classes are explored with particular emphasis on the extent to which oxidative stressors and associated ischemia-reperfusion tissue injury contribute to major symptoms. The four major categories of pharmaceutical agents used for the prevention of and therapy for CVD: statins, beta blockers (ß-blockers), blood thinners (anticoagulants), and aspirin, are presented along with their adverse effects. Analyses of major cellular and molecular features of drug- and NMM-mediated cardioprotective processes are provided in the context of their development for human clinical application. Future directions of the evolving research described here will be particularly focused on the characterization and manipulation of calcium- and calcineurin-mediated cascades of signaling from cell surface receptors on cardiovascular and immune cells to the nucleus, with the emergence of both protective and pathological epigenetic features that may be modulated by synergistically-acting combinations of drugs and phytochemicals in which phytochemicals interact with cells to promote signaling that reduces the effective dosage and thus (often) toxicity of drugs.

A review of multi-threat medical countermeasures against chemical warfare and terrorism.

The Multi-Threat Medical Countermeasure (MTMC) hypothesis has been proposed with the aim of developing a single countermeasure drug with efficacy against different pathologies caused by multiple classes of chemical warfare agents. Although sites and mechanisms of action and the pathologies caused by different chemical insults vary, common biochemical signaling pathways, molecular mediators, and cellular processes provide targets for MTMC drugs. This article will review the MTMC hypothesis for blister and nerve agents and will expand the scope of the concept to include other chemicals as well as briefly consider biological agents. The article will also consider how common biochemical signaling pathways, molecular mediators, and cellular processes that contribute to clinical pathologies and syndromes may relate to the toxicity of threat agents. Discovery of MTMC provides the opportunity for the integration of diverse researchers and clinicians, and for the exploitation of cutting-edge technologies and drug discovery. The broad-spectrum nature of MTMC can augment military and civil defense to combat chemical warfare and chemical terrorism.