Converting an alcohol to an amine in a cationic lipid dramatically alters the co-lipid requirement, cellular transfection activity and the ultrastructure of DNA-cytofectin complexes.

Cytofectins are positively charged lipophilic molecules that readily form complexes with DNA and other anionic polynucleotides. Normally, cytofectins are combined with an activity-augmenting phospholipid such as dioleoylphosphatidylethanolamine (DOPE), and a film of dried, mixed lipid is prepared and hydrated to form cationic liposomes. The liposome solution is then mixed with a plasmid DNA solution to afford cytofectin-DNA complexes which, when presented to living cells, are internalized and the transgene is expressed. One of the most potent cytofectins, dimyristoyl Rosenthal inhibitor ether (DMRIE), is presently being used to deliver transcriptionally active DNA into human tumor tissues. Here we report the remarkable consequences of replacing the alcohol moiety of DMRIE with a primary amine. The resulting cytofectin, called beta-aminoethyl-DMRIE (betaAE-DMRIE), promoted high level transfection over a broad range of DNA and cationic lipid concentrations. A comparison of in vitro transfection activity between DMRIE and betaAE-DMRIE in 10 cell types revealed that betaAE-DMRIE was more active than DMRIE, and that betaAE-DMRIE, unlike DMRIE, was maximally effective in the absence of colipid. The consequences of the alcohol-to-amine conversion on the structure of the cytofectin/DNA complex was also examined by Atomic Force Microscopy. Strikingly dissimilar images were found for plasmid DNA alone and for the plasmid complexes of betaAE-DMRIE and DMRIE/DOPE.

Candidal suppurative peripheral thrombophlebitis: recognition, prevention, and management.

Candida species are seldom considered as a cause of suppurative peripheral thrombophlebitis. During a 15-month period in a 291-bed acute-care hospital, candidal suppurative peripheral thrombophlebitis developed in seven patients. All patients had fever, a tender palpable cord, and Candida species isolated from resected veins and/or pus expressed at the catheter entrance site. Four patients had candidemia. None were neutropenic or recipients of corticosteroids. All had concomitant or preceding bacterial infections, and had received a median of 5 antibiotics (range 3 to 9) for at least 2 weeks. Five of seven had documented preceding candidal colonization associated with broad spectrum antibiotic therapy. Catheter sites had not been routinely rotated and local catheter site care was deficient. Risk factors of antibiotics and duration of hospitalization were fewer in patients with bacterial suppurative thrombophlebitis. Combined segmental venous resection and intravenous amphotericin B appears to be the most rational therapy for this nosocomial fungal infection.