Summary Background Erythema of rosacea is thought to result from abnormal cutaneous vasomotor activity. Brimonidine tartrate (BT) is a highly selective α2-adrenergic receptor agonist with vasoconstrictive activity. Objective To determine the optimal concentration and dose regimen of topical BT gel for the treatment of erythema of rosacea and to evaluate its efficacy and safety. Methods In study A, 122 subjects were randomized to receive a single application of BT 0·07%, 0·18%, 0·5% or vehicle. In study B (4-week treatment and 4-week follow-up), 269 subjects were randomized to receive BT 0·5% once daily, BT 0·18% once daily, vehicle once daily, BT 0·18% twice daily or vehicle twice daily. Evaluations included Clinician’s Erythema Assessment (CEA), Patient’s Self-Assessment (PSA), Chroma Meter measurements and adverse events. Results In study A, a single application of topical BT gel reduced facial erythema in a dose-dependent fashion. A significant difference between BT 0·5% and vehicle in Chroma Meter redness value was observed from 30 min to 12 h after application. In study B, BT 0·5% once daily had a statistically superior success profile (defined as a two-grade improvement on both CEA and PSA over 12 h) compared with vehicle once daily on days 1, 15 and 29 (all P < 0·001). No tachyphylaxis, rebound of erythema or aggravation of other disease signs (telangiectasia, inflammatory lesions) was observed. All regimens were safe and well tolerated with similarly low incidence of adverse events. Conclusions Once-daily BT gel 0·5% is well tolerated and provides significantly greater efficacy than vehicle gel for the treatment of moderate to severe erythema of rosacea.

These results suggest that injury to axons in the brainstem plays a major role in induction of immediate posttraumatic coma and that DAI can occur without coma.

Activation of transcription factor, nuclear factor kappa B (NF-kappaB), has been shown to play a key role in inflammatory response, neuronal survival and signaling. We investigated the regional and temporal distribution of activated NF-kappaB in rats at 1 h, 2 h, 24 h, 48 h, 1 week, 2 weeks, 1 month, 2 months, 6 months, and 1 year following brain injury in rats. Early after trauma (1-2 h), activated NF-kappaB was detected in axons, and subsequently found in the cytoplasm and nucleus of neurons by 24 h and lasting up to 1 week. In addition, by 24 h posttrauma, activated NF-kappaB was detected in microglia/macrophages and astrocytes in injured cortex. Surprisingly, this activation persisted for at least 1 year following injury in the cortex, primarily at the margins of progressively enlarging ventricle. Activated NF-kappaB was also detected in endothelial cells, as early as 1 h, and persisted for up to 1 year. These results suggest that a neuronal response to brain trauma includes the activation of NF-kappaB first in the axon with subsequent translocation to the nucleus. Furthermore, these results demonstrate that remarkably prolonged activation of NF-kappaB in glia is found in the same regions undergoing persistent atrophy, suggesting NF-kappaB activation may play a role in long-term inflammatory processes following brain trauma.

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The systemic safety profile of BT gel may be considered better than that of the ophthalmic solution.