Current and Future Drug Targets in Weight Management

Obesity will continue to be one of the leading causes of chronic disease unless the ongoing rise in the prevalence of this condition is reversed. Accumulating morbidity figures and a shortage of effective drugs have generated substantial research activity with several molecular targets being investigated. However, pharmacological modulation of body weight is extremely complex, since it is essentially a battle against one of the strongest human instincts and highly efficient mechanisms of energy uptake and storage. This review provides an overview of the different molecular strategies intended to lower body weight or adipose tissue mass. Weight-loss drugs in development include molecules intended to reduce the absorption of lipids from the GI tract, various ways to limit food intake, and compounds that increase energy expenditure or reduce adipose tissue size. A number of new preparations, including combinations of the existing drugs topiramate plus phentermine, bupropion plus naltrexone, and the selective 5-HT2C agonist lorcaserin have recently been filed for approval. Behind these leading candidates are several other potentially promising compounds and combinations currently undergoing phase II and III testing. Some interesting targets further on the horizon are also discussed

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Anatomic features of the intracranial and intracanalicular portions of ophthalmic artery: for the surgical procedures

WOS: 000238317600007PubMed ID: 16775743The intracranial and intracanalicular portions of the ophthalmic artery is suspectible to various diseases and injuries; therefore, knowledge of the microanatomy of the complex bony, dural, vascular, and neural relationships of this segment is necessary for proper diagnosis and preservation of the neurovascular structures during subfrontal, pterional and intracanalicular procedures. The artery was studied in 38 human adult cadaver specimens regarding origin, intracranial and intracanalicular portions for surgical approachs. The ophthalmic artery originated from the intradural portion of the internal carotid artery, except in 5% where the ophthalmic artery originated extradurally. The ophthalmic artery originated from medial of superior wall of internal carotid artery in 73.7%, from the central in 21% and the lateral in 5.3% of the specimens. The diameter of the ophthalmic artery at its origin was 2.25 +/- 0.3 mm on the right and 2.16 +/- 0.4 mm on the left. The intracranial and intracanalicular course of the artery was divided into short limb, angle "a", long limb, angle "b" and distal part to the apex of the orbit. Awareness of variations in anatomic structures is paramount importance both for diagnosis and treatment of vascular lesions of the brain