Challenges in the pharmacologic management of obesity and secondary dyslipidemia in children and adolescents.

The rise in childhood obesity has lead to an increased number of children with lipid abnormalities and the predominance of a combined dyslipidemic pattern characterized by a moderate-to-severe elevation in triglycerides, normal-to-mild mild elevation in LDL cholesterol and reduced HDL cholesterol. Although recently published National Heart, Lung and Blood Institute (NHLBI) guidelines represent a significant step forward in managing primary dyslipidemias in pediatric patients, there is still no general consensus regarding the pharmacologic treatment of obesity-related lipid abnormalities in children. The use of early pharmacologic intervention to control dyslipidemias and reduce cardiovascular risk in young children is only expected to increase given the steady increase in obesity and emergence of atherosclerotic disease in pre-adolescents. Despite the increasing use of lipid-lowering therapy in children over the last few years, diet and lifestyle modification remain the first line therapy. Given the challenges of instituting and maintaining lifestyle modification in pediatric patients, however, it is likely that institution of drug therapy may be required in many children. Of all the medications currently available, the fibric acid derivatives have a cholesterol lowering profile that is most likely to be effective in obese children with the high TG/low HDL phenotype and data from a recently published study of gemfibrozil in children with metabolic syndrome are promising. However, additional information regarding the short and long-term safety and efficacy of fibrate therapy in children with obesity-related lipid disorders is needed before use of these agents can be recommended.

Environmental sensitivity of Ru(II) complexes: the role of the accessory ligands.

A suite of Ru(II) complexes in which one ligand is pH responsive and the other two are varied in an effort to achieve improved photophysics has been synthesized and their potential as pH reporters assessed. The more general purpose of the study was to examine the role of the accessory ligands in heteroleptic reporter complexes and the degree to which such ligands can affect the performance of luminescent reporters. For this suite of complexes, judicious choice of the accessory ligand can alter both the pK(a)* and the dynamic range of response. It was found that the emission color and brightness were influenced by pH, but the lifetimes were only weakly affected. Surprisingly, some accessory ligands which should have improved luminescent properties essentially turned off the pH response. Several possible reasons for this observation are explored. It is suggested, and density functional theory (DFT) calculations support, that the relative π* levels of the pH sensitive and the accessory ligands are critical.