The new era of anticoagulation.

Warfarin has been approved by the U.S. Food and Drug Administration for medical use as an anticoagulant for more than 60 years. Although it has been an effective anticoagulant, its use is accompanied by several pitfalls, which has led to research and the discovery of new additional groups of anticoagulants: direct thrombin inhibitors, such as dabigatran, and direct factor Xa inhibitors, such as rivaroxaban and apixaban. These new anticoagulants are fast-acting, noninferior to warfarin in preventing stroke in patients with nonvalvular atrial fibrillation, and do not require monitoring. More data are accumulating to support their use in the prevention and management of venous thromboembolism. This article reviews the literature on these novel anticoagulants, including their pharmacokinetics and treatment indications.

Concurrent Takayasu arteritis with common variable immunodeficiency and moyamoya disease.

Takayasu arteritis is a rare, chronic form of large vessel vasculitis that characteristically involves the aorta and its branches. Its origin and disease process are currently unknown, although T lymphocytes and, most recently, B cells are thought to play a role. Common variable immunodeficiency (CVID) is a collection of heterogeneous disorders resulting in an antibody deficiency and recurrent infections, and is the most common symptomatic primary immunodeficiency disorder. This report presents a unique case of possible Takayasu arteritis with a history of CVID in a young man admitted with multiple cerebrovascular accidents. Takayasu arteritis may serve as the main cause of this presentation. The rarity of this case is further accentuated by the presence of moyamoya disease. Finally, the possible disease process and novel treatment of Takayasu arteritis is discussed briefly.

Disruption of gene expression rhythms in mice lacking secretory vesicle proteins IA-2 and IA-2ß.

Insulinoma-associated protein (IA)-2 and IA-2ß are transmembrane proteins involved in neurotransmitter secretion. Mice with targeted disruption of both IA-2 and IA-2ß (double-knockout, or DKO mice) have numerous endocrine and physiological disruptions, including disruption of circadian and diurnal rhythms. In the present study, we have assessed the impact of disruption of IA-2 and IA-2ß on molecular rhythms in the brain and peripheral oscillators. We used in situ hybridization to assess molecular rhythms in the hypothalamic suprachiasmatic nuclei (SCN) of wild-type (WT) and DKO mice. The results indicate significant disruption of molecular rhythmicity in the SCN, which serves as the central pacemaker regulating circadian behavior. We also used quantitative PCR to assess gene expression rhythms in peripheral tissues of DKO, single-knockout, and WT mice. The results indicate significant attenuation of gene expression rhythms in several peripheral tissues of DKO mice but not in either single knockout. To distinguish whether this reduction in rhythmicity reflects defective oscillatory function in peripheral tissues or lack of entrainment of peripheral tissues, animals were injected with dexamethasone daily for 15 days, and then molecular rhythms were assessed throughout the day after discontinuation of injections. Dexamethasone injections improved gene expression rhythms in liver and heart of DKO mice. These results are consistent with the hypothesis that peripheral tissues of DKO mice have a functioning circadian clockwork, but rhythmicity is greatly reduced in the absence of robust, rhythmic physiological signals originating from the SCN. Thus, IA-2 and IA-2ß play an important role in the regulation of circadian rhythms, likely through their participation in neurochemical communication among SCN neurons.