Timely topics in medicine. Cardiovascular diseases最新文献

Since its discovery as the first receptor for the orexigenic neuropeptide melanin-concentrating hormone (MCH), the MCH receptor, MCHR1, has been actively pursued for therapeutic intervention in the treatment of obesity. Mice with targeted deletion of MCHR1 or its cognate ligand, MCH, generally have decreased body weight and fat mass and are resistant to diet-induced obesity compared with their wild-type counterparts. Mice treated via intracerebroventricular infusion with MCH, or that overexpress MCH or MCHR1, exhibit weight gain compared with control animals. MCHR1 is also a central target of leptin signaling and appears to be a mediator of insulin resistance. The distribution of MCH and MCHR1 in rat brain, outside of regions that control appetite and satiety, has led to the finding that MCH signaling participates in other functions such as emotion and stress. This review will describe in detail the biological studies that show how MCH and MCHR1 control numerous physiological functions. The current status of the development of MCHR1 antagonists for clinical use will also be assessed. Given the substantial link between obesity and its many associated afflictions, a single pharmaceutical agent that could be used to treat multiple pathologies would be welcome.

In the nearly 130 years since Trousseau first described migratory thrombophlebitis in cancer patients, thromboembolism has become a well-established presenting sign and complication of cancer. The coagulation system is activated in cancer and is further amplified by treatment with chemotherapy, radiation or surgery. Hypercoagulation is documented in virtually all cancer types, albeit at different rates, and is the second leading cause of death in cancer patients. The relationship between clotting activation and carcinogenesis supports the view of cancer as a hypercoagulable state and holds implications for the development of thrombosis, enhancement of tumor growth and risk of poor clinical outcomes. Although it is well recognized that cancer can activate the coagulation cascade, it is less well known that activation of the coagulation system may also support tumor progression. Additionally, platelet activation in cancer patients and its impact on tumor progression and metastasis further expand the role of the hemostatic system in malignancy. The problem of thrombosis in patients with metastatic diseases is a serious concern for clinicians. This review explores the mechanisms and clinical implications of coagulation and platelet activation in cancer. The prevention and treatment of venous thromboembolism in cancer will also be discussed by reviewing data from key clinical investigations. Finally, the emerging role of low-molecular-weight heparin as an antineoplastic agent will be explored. Warfarin and unfractionated heparin have been in clinical use for more than 50 years. Both are effective anticoagulants, but their use is associated with a number of impediments, including the need for intensive coagulation monitoring, wide variation in dose-response relationships, multiple drug interactions (in the case of warfarin), and serious immune-mediated thrombocytopenia (in the case of heparin). The introduction of low-molecular weight heparin advanced anticoagulation therapy by enhancing efficacy and eliminating the need for intensive coagulation monitoring. Fondaparinux, the first selective factor Xa inhibitor, represents yet another improvement in anticoagulation therapy. By binding rapidly and strongly to antithrombin, its sole physiologic target in plasma, fondaparinux catalyzes specifically the inhibition of factor Xa, which results in effective and linear dose-dependent inhibition of thrombin generation. Additionally, efficient inhibition of factor Xa activity impairs the activation of tissue factor/factor VIIa complex leading to downregulation of procoagulant state, pro-angiogenesis, and proinflammatory factors induced by tissue factor/factor VIIa. Furthermore, a number of orally active direct antithrombin and anti-factor Xa are in advanced clinical development for various thromboembolic disorders.

The 31st International Stroke Conference, held February 16-18, 2006, in Kissimmee, Florida, U.S.A., highlighted more than 550 presentations emphasizing basic and translational sciences and explored how these sciences evolve to unlock our understanding of stroke pathophysiology with the aim of developing more effective prevention diagnosis and treatment tools. This year's conference reached record attendance, with more than 4,000 participants. In this report we will focus on new diagnostic and therapeutic stroke targets addressed in the meeting, together with the trends in neurovascular research presented at the oral and poster sessions of this two-and-a-half day congress.

Hyperprolactinemia is the most common biochemical abnormality currently encountered in clinical endocrinology. Hyperprolactinemic syndromes are a diverse group of disorders that are common in both men and women. Once the diagnosis of hyperprolactinemia has been established, the patient should be screened for the numerous causes of hormone hypersecretion. Hence, an accurate medical history is extremely important for the clinician to find out the most frequent causes of hypersecretion of prolactin (e.g., drugs). Clinicians should be aware of the possibility of prolactin elevation and associated problems with any drug that has the potential to cause hyperprolactinemia, particularly in patients who have other factors that might stimulate prolactin release.