nisms of ACh-mediated vasodilation in the forearm cutaneous microcirculation. J Appl Physiol 92: 780-788, 2002; 10.1152/japplphysiol.01167.2000.-The relative contribution of endothelial vasodilating factors to acetylcholine (ACh)-mediated vasodilation in the forearm cutaneous microcirculation is unclear. The aims of this study were to investigate the contributions of prostanoids and cutaneous C fibers to basal cutaneous blood flow (CuBF) and ACh-mediated vasodilation. ACh was iontophoresed into the forearm, and cutaneous perfusion was measured by laser-Doppler flowmetry. To inhibit the production of prostanoids, four doses of acetylsalicylic acid (ASA; 81, 648, 972, and 1,944 mg) were administered orally. Cutaneous nerve fibers were blocked with topical anesthesia. Cyclooxygenase inhibition did not change basal CuBF or endothelium-mediated vasodilation to ACh. In contrast, ASA (972 and 1,944 mg) significantly reduced the C-fiber-mediated axon reflex in a dose-dependent fashion. Blockade of C-fiber function significantly reduced axon reflex-mediated vasodilation but did not affect basal CuBF or endothelium-dependent vasodilation. The findings suggest that prostanoids do not contribute significantly to basal CuBF or endothelium-dependent vasodilation in the forearm microcirculation. In contrast, prostanoids are mediators of the ACh-provoked axon reflex. endothelium; prostaglandin; nitric oxide; axon reflex; acetylcholine CUTANEOUS BLOOD FLOW (CuBF) is regulated by endothelial, neural, and humoral factors. The interaction between these mechanisms of blood flow control is poorly defined. Recent studies of CuBF have used the technique of laser-Doppler flowmetry in combination with the iontophoretic application of charged vasoactive agents. Acetylcholine (ACh) has been used to induce endothelium-mediated blood flow, and the direct nitric oxide (NO) donor sodium nitroprusside has been used to provoke non-endothelium-mediated blood flow. Despite the widespread use of ACh-evoked vasodilation in studies investigating vascular physiology and pathophysiology, the mechanisms responsible for its effect, particularly in the cutaneous microcirculation, are unresolved. This question has important implications. If prostaglandins do play a major role in endotheliummediated vasodilation, some effects of acetylsalicylic acid (ASA) therapy, which is extensively used for its prophylactic antiplatelet effect in patients with cardiovascular and cerebrovascular disease (17, 27), may be counterproductive. Furthermore, if prostaglandins play a major role in the C-fiber-mediated axon reflex, reduction of this reflex by cyclooxygenase inhibition may attenuate the ability to mount a neurogenic inflammatory response (4, 48). Attenuation of this important protective reflex in patients with peripheral neuropathy impairs wound healing and increases susceptibility to infection, thereby leading to cutaneous ulceration, gangrene, and ultimately amputation (3,21).Factors released by the endothelium in response to ACh include NO, vasoactive prostanoi...

Multiple sclerosis is a complex, autoimmune-mediated disease of the central nervous system characterized by inflammatory demyelination and axonal/neuronal damage. The approval of various disease-modifying therapies and our increased understanding of disease mechanisms and evolution in recent years have significantly changed the prognosis and course of the disease. This update of the Multiple Sclerosis Therapy Consensus Group treatment recommendation focuses on the most important recommendations for disease-modifying therapies of multiple sclerosis in 2021. Our recommendations are based on current scientific evidence and apply to those medications approved in wide parts of Europe, particularly German-speaking countries (Germany, Austria, and Switzerland).

Changes in cutaneous blood flow are seen relatively early in the course of diabetic peripheral neuropathy and are characterized by endothelial and neural but not smooth muscle dysfunction. The presence of significant C-fiber impairment in both diabetic groups, together with significantly greater dysfunction in endothelium-dependent vasodilation in type 2 diabetics, suggests that the endothelial function and nitric oxide may play a greater role in the pathogenesis of diabetic peripheral neuropathy in type 2 diabetic patients.

Objective To evaluate the efficacy of an evidencebased patient information programme aiming to increase informed choice in patients with early multiple sclerosis (MS). Background Patients with early MS face a number of uncertainties concerning diagnosis, prognosis and effectiveness of immunotherapy. Prior studies suggest that evidence-based patient information combined with group education can promote informed choice in MS patients. Methods A 12-month, six-centre, double-blind randomised controlled clinical trial with 192 patients with a diagnosis of confirmed relapsing-remitting MS or clinical isolated syndrome in Germany. A 4-h interactive evidence-based educational programme was compared with a 4-h MS-specific stress management programme. The primary endpoint was informed choice after 6 months comprising risk knowledge and congruency between attitude towards immunotherapy and actual immunotherapy uptake. Secondary endpoints included autonomy preference, decision autonomy, decisional conflict and satisfaction, anxiety and depression, and number of immunotherapies. Results For the primary endpoint, a significant difference was shown with 50 of 85 (59%) participants in the intervention group achieving informed choice after 6 months compared with 18 of 89 (20%) in the control group (OR 0.2 (95% CI 0.1 to 0.4), p<0.001). Four weeks after the intervention, more participants in the intervention group showed good risk knowledge (difference between groups 39% (95% CI 26% to 53%), p<0.001). There were no significant differences between groups for attitude towards immunotherapy and for immunotherapy uptake. There were trends towards increased autonomy preference after the intervention and increased adherence to immunotherapies in the intervention group. Conclusions The intervention significantly increased informed choice and relevant risk knowledge without negative side effects.