Neuronal expression and regulation of CGRP promoter activity following viral gene transfer into cultured trigeminal ganglia neurons.

We have examined the regulation of calcitonin gene-related peptide (CGRP) promoter activity in primary cultures of rat trigeminal ganglia neurons. A viral vector was used to circumvent the potential complication of examining only a small subpopulation of cells in the heterogeneous cultures. Infection with high titers of recombinant adenovirus containing 1.25 kb of the rat CGRP promoter linked to the beta-galactosidase reporter gene (AdCGRP-lacZ) yielded expression in about 50% of the CGRP-expressing neurons. The CGRP-lacZ reporter gene was preferentially expressed in neurons, with 91% co-expression with endogenous CGRP. In contrast, an adenoviral vector containing a CMV-lacZ reporter was predominantly expressed in non-neuronal cells, with only 29% co-expression with CGRP. We then asked whether the CGRP promoter in the viral vector could be regulated by serotonin receptor type 1 (5-HT(1)) agonists. Promoter activity was decreased two- to threefold by treatment with five 5-HT(1B/D) agonists, including the triptan drugs sumatriptan, eletriptan, and rizatriptan that are used for migraine treatment. As controls, CMV promoter activity was not affected, and 5-HT(1B/D) receptor antagonists blocked the repression caused by sumatriptan and eletriptan. Thus, adenoviral gene transfer can be used in trigeminal ganglia neurons for studying the mechanisms of triptan drug action on CGRP synthesis.

Adoption of new technologies for early detection of melanoma in dermatologic practice.

The identification and diagnosis of early melanoma will reduce unnecessary operations and may be important in reducing mortality from melanoma and impacting cost savings to the health system. New technologies are being developed and used at some specialized centers to facilitate the detection and diagnosis of early melanoma for patients at high risk. These technologies include but are not limited to digital photography, dermoscopy, computerized image analysis systems, and confocal scanning laser microscopy. To most effectively implement these novel approaches, it is important to identify the key factors that influence the adoption or diffusion of new medical technologies. We propose patient-, physician-, and health care system-related factors that influence the diffusion of new technologies for the early detection of skin cancer. Studies involving physicians and patients in a variety of clinical settings need to be conducted to achieve a greater understanding of the barriers to the adoption of these new technologic tools that are intended to aid in skin cancer screening.