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D Roling

Publications and source records attributed to D Roling.

3 recordsLinked to original sources

Failure to demonstrate therapeutic tachyphylaxis to topically applied steroids in patients with psoriasis.

BACKGROUND: Tachyphylaxis, defined as a rapidly decreasing response to a physiologically active agent after administration of a few doses, can be well demonstrated in the experimental setting. However, tachyphylaxis in the clinical setting lacks clear demonstration. OBJECTIVE: Our purpose was to identify dermatologists' perception of the clinical incidence of tachyphylaxis and then design a prospective study that would estimate the clinical incidence of tachyphylaxis. METHODS: Clinical and academic dermatologists completed a survey questionnaire about the incidence of tachyphylaxis and the time course to its occurrence. Subjects with plaque psoriasis applied topical corticosteroid twice daily for 12 weeks to their plaques, leaving an isolated plaque untreated for comparison. Plaques were evaluated every 2 weeks. By means of a 9-point scale, an end point for clinical detection of tachyphylaxis was defined as "an increase in plaque elevation of at least 2 occurring after a detectable decrease in plaque elevation with topical steroid." RESULTS: The survey found that 57% of dermatologists perceived that tachyphylaxis occurred after 8 weeks of therapy with topical corticosteroid. In the 12-week clinical study, none of 32 patients exhibited detectable signs of tachyphylaxis. CONCLUSION: What accounts for the commonly held belief of tachyphylaxis in the clinical setting may be related to the therapeutic efficacy of topical corticosteroids. Failure of topical corticosteroids to clear psoriasis after an initial improvement may give the impression of tachyphylaxis. The common clinical perception of tachyphylaxis may also be related to issues of compliance outside a study setting or a psoriasis flare unrelated to therapy.

Administration, Topical↗

Expression of growth-associated protein-43 kD in Schwann cells is regulated by axon-Schwann cell interactions and cAMP.

We have examined the regulation of growth-associated protein 43 kD (GAP-43) in rat Schwann cells. In unlesioned adult nerves, GAP-43-immunoreactivity was restricted to non-myelinating Schwann cells and unmyelinated axons. When adult nerves were transected to cause permanent axotomy, previously myelinating Schwann cells expressed progressively more GAP-43-immunoreactivity over 3 weeks, and GAP-43 mRNA levels increased over a similar time course. The peak level of GAP-43 mRNA occurred at least 2 weeks later than that of nerve growth factor receptor, another marker of denervated Schwann cells. In contrast, after nerve-crush, which allows axonal regeneration, many fewer Schwann cells had GAP-43-immunoreactivity, and the amount of GAP-43 mRNA was markedly lower than in transected nerves. Forskolin, a drug that activates adenylate cyclase and mimics many effects of axon-Schwann cell interactions, markedly reduced GAP-43-immunoreactivity and mRNA expression in cultured Schwann cells, whereas interleukin-1 had no effect. These data demonstrate that axon-Schwann cell interactions inhibit the expression of GAP-43 in Schwann cells and that this effect is mimicked by forskolin.

Animals↗