The peroxisome proliferator-activated receptors (PPARs) are a family of fatty acid-activated transcription factors which control lipid homeostasis and cellular differentiation. PPAR␣ (NR1C1) controls lipid oxidation and clearance in hepatocytes and PPAR␥ (NR1C3) promotes preadipocyte differentiation and lipogenesis. Drugs that activate PPAR␣ are effective in lowering plasma levels of lipids and have been used in the management of hyperlipidemia. PPAR␥ agonists increase insulin sensitivity and are used in the management of type 2 diabetes. In contrast, there are no marketed drugs that selectively target PPAR␦ (NR1C2) and the physiological roles of PPAR␦ are unclear. In this report we demonstrate that the expression of PPAR␦ is increased during the differentiation of human macrophages in vitro. In addition, a highly selective agonist of PPAR␦ (compound F) promotes lipid accumulation in primary human macrophages and in macrophages derived from the human monocytic cell line, THP-1. Compound F increases the expression of genes involved in lipid uptake and storage such as the class A and B scavenger receptors (SRA, CD36) and adipophilin. PPAR␦ activation also represses key genes involved in lipid metabolism and efflux, i.e. cholesterol 27-hydroxylase and apolipoprotein E. We have generated THP-1 sublines that overexpress PPAR␦ and have confirmed that PPAR␦ is a powerful promoter of macrophage lipid accumulation. These data suggest that PPAR␦ may play a role in the pathology of diseases associated with lipidfilled macrophages, such as atherosclerosis, arthritis, and neurodegeneration.

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Our aim was to measure the adherence to Artemisinin based Combination Therapy and to determine patient related factors that affect adherence. Three hundred (300) patients receiving ACT treatment dispensed from the community pharmacy were randomly selected and followed up on the fourth day after the start of their three-day therapy to assess adherence. Adherence was measured by pill count. Quantitative interviews using a semistructured questionnaire were used to assess patients' knowledge and beliefs on malaria and its treatment. Adherence levels to the ACTs were 57.3%. Patient related factors that affected adherence to ACTs were patients' knowledge on the dosage (P = 0.007; v = 0.457), efficacy (P = 0.009; v = 0.377), and side effects (P = 0.000; v = 0.403) of the ACTs used for the management of malaria, patients' awareness of the consequences of not completing the doses of antimalarial dispensed (P = 0.001; v = 0.309), and patients' belief that “natural remedies are safer than medicines” and “prescribers place too much trust in medicines.” There was no significant relationship between adherence and patients' knowledge on the causes, signs, and symptoms of malaria. There is the need for pharmacy staff to stress on these variables when counseling patients on antimalarials as these affect adherence levels.

Dyslipidaemias, particularly those characterized by the 'atherogenic profile' of high low-density lipoprotein-cholesterol and triglycerides and low high-density lipoprotein-cholesterol, are the major modifiable risk factor for atherosclerosis. The search for drugs to favourably alter such lipid profiles, reducing the associated morbidity and mortality, remains a major research focus. Niacin (nicotinic acid) is the most effective agent available for increasing high-density lipoprotein-cholesterol, but its use is associated with side effects that negatively affect patient compliance: these appear to arise largely as a result of production of prostaglandin D2 and its subsequent activation of the DP1 receptor. Desire to reduce the side effects (and improve pharmacokinetic parameters) has led to the development of a number of agonists that have differing effects, both in terms of clinical potency and the severity of adverse effects. The recent discovery of the niacin G-protein-coupled receptor HM74A (GPR109A) has clarified the distinction between the mechanism whereby niacin exerts its therapeutic effects and the mechanisms responsible for the generation of side effects. This has allowed the development of new drugs that show great potential for the treatment of dyslipidaemia. However, recent advances in understanding of the contribution of prostaglandin metabolism to vascular wall health suggest that some of the beneficial effects of niacin may well result from activation of the same pathways responsible for the adverse reactions. The purpose of this review is to emphasize that the search for agonists that show higher tolerability must take into account all aspects of signalling through this receptor.