Microdialysis sampling of lipophilic molecules in human tissues is challenging because protein binding and adhesion to the membrane limit recovery. Hydroxypropyl-ß-cyclodextrin (HP-ß-CD) forms complexes with hydrophobic molecules thereby improving microdialysis recovery of lipophilic molecules in vitro and in rodents. We tested the approach in human subjects. First, we determined HP-ß-CD influe...

In skin and hair research drug targeting to the hair follicle is of great interest. Therefore the influence of permeant lipophilicity and vehicle composition on local accumulation has been examined using confocal laser scanning microscopy (CLSM). Formulations saturated with either Oregon Green 488, Bodipy FL C(5) or Bodipy 564/570 C(5) were prepared. The dyes were applied in citric acid buffer,...

Nitrogen-containing bisphosphonates, drugs used to treat bone resorption diseases, also have activity against a broad range of protists, including blood-stage Plasmodium spp. Here, we show that new-generation "lipophilic" bisphosphonates designed as anticancer agents that block protein prenylation also have potent activity against Plasmodium liver stages, with a high (>100) therapeutic index. T...

This review describes the synthesis and structure-activity relationship (SAR) study of muraymycins (MRYs), which are potent antibacterial nucleoside antibiotics. The key elements of our synthetic approach include the preparation of L-epi-capreomycidine via a C-H amination reaction and a convergent assemblage to construct of the framework of MRYs using Ugi four component reaction. With this appr...

A new type of 5'-lipophilic capture tag is described, enabling the facile reverse phase HPLC purification of chemically modified hammerhead ribozymes (oligozymes) whilst still carrying the 2'-O-tert.-butyldimethylsilyl protection of the essential riboses. In its most convenient form, the capture tag consists of a simple diol, such as hexan-1,6-diol, which at one end is attached via a silyl resi...

BACKGROUND Statins substantially reduce cardiovascular mortality and appear to have beneficial effects independent of their lipid-lowering properties. We evaluated the hypothesis that statin use may modulate the secretion of aldosterone, a well-known contributor to cardiovascular disease. METHODS AND RESULTS We measured adrenal hormones in 2 intervention studies. In study 1 in hypertensive su...

Recent reports have suggested that statins induce cell death in certain epithelial cancers and that patients taking statins to reduce cholesterol levels possess lower cancer incidence. However, little is known about the mechanisms of action of different statins or the effects of these statins in gynaecological malignancies. The apoptotic potential of two lipophilic statins (lovastatin and simva...

The understanding of the molecular mechanisms leading to peptide action entails the identification of a core active site. The major 28-aa neuropeptide, vasoactive intestinal peptide (VIP), provides neuroprotection. A lipophilic derivative with a stearyl moiety at the N-terminal and norleucine residue replacing the Met-17 was 100-fold more potent than VIP in promoting neuronal survival, acting a...