Abstract: Adult mesenchymal stem cells (MSCs) are non-hematopoietic cells with multi-lineage potential to differentiate into various tissues of mesodermal origin. They can be isolated from bone marrow and other tissues and have the capacity to extensively proliferate in vitro. Moreover, MSCs have also been shown to produce anti-inflammatory molecules which can modulate humoral and cellular immune responses. Considering their regenerative potential and immunoregulatory effect, MSC therapy is a promising tool in the treatment of degenerative, inflammatory, and autoimmune diseases. However, the current understanding from results of clinical trials is that MSC-therapy is safe but its therapeutic efficiency needs to be improved. In this article we will focus on options for genetic manipulation of MSCs and on current progress in adapting genetically-modified MSCs for clinical use in acute cardiovascular disease. ... Read more

Abstract: The idea of promoting angiogenesis in ischemic tissues remains an undisputed therapeutic approach for the treatment of myocardium and skeletal muscles that lack sufficient blood supply. However, clinical experiences from several large trials indicated that delivery of proangiogenic factors to patients suffering from myocardial infarction and leg ischemia has not shown significant benefits. Despite continuous success in various animal disease models, why has this simple principle not shown proof of concept in patients? What has been missing in the trial deign? What are the differences between animal models and patients? What are the optimal components for promoting functional collateral networks? This brief review discusses molecular mechanisms underlying arteriogenesis and proposes novel approaches for improvement of therapeutic outcomes. ... Read more

Abstract: Anti-platelet drugs play a key role in cardiovascular medicine since the introduction of aspirin as an anti-thrombotic agent some 50 years ago. After many years of a "monopoly" of aspirin, ADP receptor P2Y12 inhibitors were introduced with a significant improvement in clinical outcome. Nowadays dual anti-platelet therapy is the common practice for both acute events and secondary prevention in selected groups of patients. The improved efficacy of multiple drug therapy is associated with an increased risk of bleeding, which raises the issue of the dosing of these drugs. Recently, numerous studies have reported a variable laboratory response to aspirin and clopidogrel, which correlates with clinical outcome. Several mechanisms for causing this variable response have been proposed, including genetic variability, disease burden, and others. A major obstacle in this field is the lack of a standardized method for testing these responses. New drugs are currently under different stages of development, including new P2Y12 receptors inhibitors, thrombaxane receptor blockers, direct thrombin inhibitors, and inhibitors for other signaling pathways including oral GPIIbIIIa inhibitors. Thus anti-platelet therapy is currently under intensive developments toward multiple drug therapy and personal dose adjustment, which may improve clinical outcome. ... Read more

Abstract: Vitamin K antagonists (VKA), such as warfarin, have been the only available oral anticoagulants despite their many limitations. The greatest medical need is to find a replacement for warfarin for long-term therapy, particularly for stroke prevention in atrial fibrillation (AF) patients. Emerging oral anticoagulants are free from many of warfarin's drawbacks and may offer a convenient alternative. Drugs in advanced development target factor Xa (rivaroxaban, apixaban) or thrombin (dabigatran etexilate). Recently, the RE-LY phase III study found dabigatran etexilate was an effective and convenient alternative to warfarin in stroke prevention for AF patients. Within the next two years, similar studies comparing rivaroxaban and apixaban versus warfarin in AF patients will become available. This paper reviews warfarin's limitations, discusses the pharmacokinetics of emerging anticoagulants in advanced development, and summarizes trials with an emphasis on head-to-head studies comparing novel anticoagulants to warfarin. ... Read more

Abstract: Human adult bone marrow-derived multipotent stem cells (BMSC) can grow to become virtually any cell type, under the right conditions. Heart muscle cells differentiated from BMSC are shown to be able to repair lesions caused by a heart attack. ... Read more

Abstract: Stem cells have a great potential in regenerative medicine. Among their many capabilities, for example, they can become heart muscle cells when they are grown in a specially formulated "juice" in culture. These stem cells-derived heart muscle cells can be transplanted into the heart where they integrate into resident heart muscle and function as a pacemaker. Many technical issues remain to be addressed before stem cells can be used therapeutically. ... Read more

In 1997, deCODE Genetics, Inc., a genomics biotechnology company based at Teykjavik, Iceland, proposed to the Icelandic Ministry of Health that a centralized database on health care in Iceland be established for gaining new knowledge and insight about common diseases and for serving as a model system for individualized healthcare practice in a nation. A bill was drafted and debated nationwide, primarily on bioethics and privacy grounds, and passed by the Icelandic Parliament by approximately 75% of the votes in December 1998.

The bill stipulated, among other specific instructions such as community consent, partnership with the community, consent of individuals, and ... Read more

Researchers at deCODE Genetics led by CEO Dr. Kari Stefansson compared the genomes of 713 heart attack patients contained in the Icelandic Healthcare Database (see pages 72 and 78) with those of normal individuals and discovered a cluster of gene variations on the ALOX5AP gene. The gene encodes 5-lipoxygenase activating protein (FLAP) and its variants are associated with a twofold increased risk of heart attacks and stroke (Helgadottir A et al., Nat Genet 36:233-239, March 2004).

A key product generated by the FLAP-stimulated pathway is leukotriene B4, an important factor that contributes to inflammation and plaque formation on arterial walls. The ... Read more

The finding that a single deletion of 21 base pairs (7 amino acids) in a gene causes heart attack with a 100% probability was recently reported in Science (Wang L et al., Science 302:1578-1581, Nov. 28, 2003) by a research team led by Drs. Qing Wang and Eric J. Topol of Cleveland Clinic Foundation, Cleveland, OH.

The gene is MEF2A, whose protein product controls the development of muscle tissue including the muscle in the wall of coronary arteries. The researchers performed a whole genome analysis on 21 members of a large family with a history of heart disease. The mutated MEF2A ... Read more

Other Names: eplerenone.

Maker: Pfizer.

Disease Treated: Congestive heart failure post-myocardial infarction and hypertension.

Approval Status: Approved for congestive heart failure post-myocardial infarction on October 8, 2003, and for hypertension on September 30, 2002.

Chemical/Biological Nature: INSPRA is a small molecule chemical compound. It has a molecular weight of 414.50 daltons.

Administration: INSPRA is taken orally once or twice daily . For treating congestive heart failure post-myocardial infarction, the recommended starting dose is 25 mg once daily and can be increased to 50 mg once daily. For treating hypertension, the recommended dosage is 50 mg once daily and can be increased to 50 mg twice ... Read more