PubMed · 3769783
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1986-03-10. Difflam--a topical NSAID.. https://pubmed.ncbi.nlm.nih.gov/3769783/
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The adult cortex is thought to undergo plastic changes that are closely dependent on neuronal activity (reviewed in ref. 1), although it is not yet known what molecules are involved. Neurotrophins and their receptors have been implicated in several aspects of developmental plasticity, and their expression in the adult cortex suggests additional roles in adult plasticity. To examine these potential roles in vivo, we used intrinsic-signal optical imaging to quantify the effects of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) on the functional representation of a stimulated whisker in the 'barrel' subdivision of the rat somatosensory cortex. Topical application of BDNF resulted in a rapid and long-lasting decrease in the size of a whisker representation, and a decrease in the amplitude of the activity-dependent intrinsic signal. In contrast, NGF application resulted in a rapid but transient increase in the size of a representation, and an increase in the amplitude of the activity-dependent intrinsic signal. These results demonstrate that neurotrophins can rapidly modulate stimulus-dependent activity in adult cortex, and suggest a role for neurotrophins in regulating adult cortical plasticity.
OBJECTIVE: To examine the effectiveness in treating impotence to topically applied cream containing three vasodilators--aminophylline, isosorbide dinitrate, and co-dergocrine mesylate--which act by different mechanisms. DESIGN: Randomised double blinded placebo controlled crossover trial over two weeks. SUBJECTS: 36 men with erectile dysfunction randomly allocated to two equal groups. INTERVENTIONS: Active cream containing aminophylline 3%, isosorbide dinitrate 0.25%, and co-dergocrine mesylate 0.05% for one week and placebo for another. MAIN OUTCOME MEASURES: Patients' reported experience of penile responses and side effects of treatment in questionnaires. Penile tumescence and arterial flow in the laboratory. RESULTS: 21 patients reported full erection and satisfactory intercourse with the active cream. Three men reported full erection and satisfactory intercourse with either cream. The active cream was more effective in psychogenic than organic impotence (eight out of nine men with psychogenic impotence achieved a full erection upsilon four out of eight with neurogenic impotence and two out of seven with arterial insufficiency). No major side effects were reported. In the laboratory the active cream increased penile arterial flow (0.19 (SD 0.08) m/s upsilon 0.02 (0.15) m/s with placebo) and induced tumescence in 24 patients. CONCLUSIONS: Topical treatment with a cream containing three different vasodilators might be considered before intracavernous injection of vasoactive agents, particularly in psychogenic impotence.
Anthralin is one of the most effective and safest therapeutic agents for the treatment of psoriasis, a skin disease characterized by epidermal hyperproliferation and hyperkeratosis. The drug induces and inflammatory response in the skin involving the expression of cytokine and cell adhesion molecule genes that is thought to be essential for its therapeutic efficacy. Reactive oxygen intermediates (ROIs) generated in vivo during the auto-oxidation of anthralin were discussed as mediators of the inflammatory response, but it is not yet understood how this is translated into novel inflammatory gene expression. In this study, we show that at little as 10 microM anthralin can activate a prototypic form of transcription factor NF-(kappa)B, a central transcriptional regulator of inflammatory and immune responses. Two different lines of evidence show that ROIs, in particular H2O2, are second messengers for the anthralin-induced NF-(kappa)B activation. Firstly, the activation could be inhibited by the structurally unrelated antioxidants N-acetyl-L-cysteine and pyrrolidinedithiocarbamate. Secondly, keratinocytes stably overexpressing catalase showed a significant reduction of NF-(kappa)B activation, while stable overexpression of Cu/Zn-superoxide dismutase augmented the anthralin effect. Our data suggest that ROI-induced NF-(kappa)B plays a role in the anti-psoriatic activity of the drug anthralin.