Thiazolidinedione drugs in the treatment of type 2 diabetes mellitus: past, present and future.

Thiazolidinedione (TZD) drugs used in the treatment of type 2 diabetes mellitus (T2DM) have proven effective in improving insulin sensitivity, hyperglycemia, and lipid metabolism. Though well tolerated by some patients, their mechanism of action as ligands of peroxisome proliferator-activated receptors (PPARs) results in the activation of several pathways in addition to those responsible for glycemic control and lipid homeostasis. These pathways, which include those related to inflammation, bone formation, and cell proliferation, may lead to adverse health outcomes. As treatment with TZDs has been associated with adverse hepatic, cardiovascular, osteological, and carcinogenic events in some studies, the role of TZDs in the treatment of T2DM continues to be debated. At the same time, new therapeutic roles for TZDs are being investigated, with new forms and isoforms currently in the pre-clinical phase for use in the prevention and treatment of some cancers, inflammatory diseases, and other conditions. The aims of this review are to provide an overview of the mechanism(s) of action of TZDs, a review of their safety for use in the treatment of T2DM, and a perspective on their current and future therapeutic roles.

Fate and developmental effects of dietary uptake of methylmercury in Silurana tropicalis tadpoles.

Adverse effects of methylmercury (MeHg) exposure during amphibian metamorphosis remain to be fully characterized. Most previous investigations determined effects of short-term exposure to elevated dose rates, without information on mercury (Hg) depuration and degradation pathways. Since metamorphosis is primarily controlled by thyroid hormones (TH), alterations in this process suggest a disruption of the TH endocrine axis. The aim of this research was to (1) characterize patterns of MeHg accumulation and depuration in tadpoles and (2) examine effects of MeHg accumulation on metamorphosis and the TH axis. Silurana tropicalis tadpoles were exposed to environmental levels of dietary MeHg until metamorphic climax. Whole-body MeHg and total Hg (THg) levels were measured, as well as the number of metamorphs, rate of metamorphosis, body size, and whole-body triiodothyronine (T3) levels at metamorphosis. Tadpoles exposed to a higher level of MeHg exhibited increased mortality and size, and reduced metamorphosis. At lower levels of MeHg, body burdens increased rapidly and eventually reached a plateau, whereas no plateau was reached at a higher level of MeHg exposure. T3 levels were not affected. Data indicate that at low and medium levels of exposure, depuration of MeHg may prevent toxicity in tadpoles. However, depuration mechanisms may be insufficient at high doses, producing disruption of metamorphosis and death. Although there were no marked effects of MeHg on whole-body T3 levels, further investigation of other components of the TH axis is warranted.

Primary care for children and adolescents with Down syndrome.

This article reviews the general health care guidelines pertaining to pediatric patients with Down syndrome and presents, in a systems-based approach, an update of the current evidence behind these guidelines. To ensure the best possible long-term outcome for these patients, clinicians should provide routine well-child examinations and immunizations while maintaining a high index of suspicion for comorbid conditions more common in Down syndrome. The primary care provider should be prepared to provide information on community resources, to coordinate care with subspecialists, and to refer to early intervention services as soon as the diagnosis is made.