Oxymetazoline hydrochloride cream for facial erythema associated with rosacea.

INTRODUCTION: Rosacea is a chronic skin condition characterized by transient and persistent erythema of the central face. The symptom of persistent erythema can be particularly frustrating for both patients and physicians as it is difficult to treat. Areas covered: Current treatment options for the treatment of rosacea include metronidazole, azelaic acid, sodium sulfacetamide-sulfur, and brimonidine. Until recently, brimonidine gel was the only option approved specifically for the treatment of facial erythema. However, oxymetazoline hydrochloride 1% cream is a newly FDA approved topical medication for adult rosacea patients. A primarily alpha-1a agonist, oxymetazoline hydrochloride (HCl) is thought to diminish erythema through vasoconstriction. Our paper seeks to evaluate evidence for topical oxymetazoline HCl with respect to its efficacy and safety for its approved indication of treating the persistent erythema associated with rosacea. Expert commentary: While assessment of available clinical trial data indicates that the medication is as effective as other available treatment for controlling rosacea-associated erythema with minimal risk of adverse effects, studies of long-term duration and direct comparison will be necessary to establish its place in treatment guidelines and clinical practice. As further evidence becomes available, the real-world clinical potential of topical oxymetazoline cream will become clearer.

Conserved determinants of lentiviral genome dimerization.

BACKGROUND: Retroviruses selectively package two copies of their unspliced genomes by what appears to be a dimerization-dependent RNA packaging mechanism. Dimerization of human immunodeficiency virus Type-1 (HIV-1) genomes is initiated by "kissing" interactions between GC-rich palindromic loop residues of a conserved hairpin (DIS), and is indirectly promoted by long-range base pairing between residues overlapping the gag start codon (AUG) and an upstream Unique 5' element (U5). The DIS and U5:AUG structures are phylogenetically conserved among divergent retroviruses, suggesting conserved functions. However, some studies suggest that the DIS of HIV-2 does not participate in dimerization, and that U5:AUG pairing inhibits, rather than promotes, genome dimerization. We prepared RNAs corresponding to native and mutant forms of the 5' leaders of HIV-1 (NL4-3 strain), HIV-2 (ROD strain), and two divergent strains of simian immunodeficiency virus (SIV; cpz-TAN1 and -US strains), and probed for potential roles of the DIS and U5:AUG base pairing on intrinsic and NC-dependent dimerization by mutagenesis, gel electrophoresis, and NMR spectroscopy. RESULTS: Dimeric forms of the native HIV-2 and SIV leaders were only detectable using running buffers that contained Mg(2+), indicating that these dimers are more labile than that of the HIV-1 leader. Mutations designed to promote U5:AUG base pairing promoted dimerization of the HIV-2 and SIV RNAs, whereas mutations that prevented U5:AUG pairing inhibited dimerization. Chimeric HIV-2 and SIV leader RNAs containing the dimer-promoting loop of HIV-1 (DIS) exhibited HIV-1 leader-like dimerization properties, whereas an HIV-1NL4-3 mutant containing the SIVcpzTAN1 DIS loop behaved like the SIVcpzTAN1 leader. The cognate NC proteins exhibited varying abilities to promote dimerization of the retroviral leader RNAs, but none were able to convert labile dimers to non-labile dimers. CONCLUSIONS: The finding that U5:AUG formation promotes dimerization of the full-length HIV-1, HIV-2, SIVcpzUS, and SIVcpzTAN1 5' leaders suggests that these retroviruses utilize a common RNA structural switch mechanism to modulate function. Differences in native and NC-dependent dimerization propensity and lability are due to variations in the compositions of the DIS loop residues rather than other sequences within the leader RNAs. Although NC is a well-known RNA chaperone, its role in dimerization has the hallmarks of a classical riboswitch.