New magnetic phase diagram of (Sr,Ca)2RuO4.

High-T(c) cuprates, iron pnictides, organic BEDT and TMTSF, alkali-doped C(60), and heavy-fermion systems have superconducting states adjacent to competing states exhibiting static antiferromagnetic or spin density wave order. This feature has promoted pictures for their superconducting pairing mediated by spin fluctuations. Sr(2)RuO(4) is another unconventional superconductor which almost certainly has a p-wave pairing. The absence of known signatures of static magnetism in the Sr-rich side of the (Ca, Sr) substitution space, however, has led to a prevailing view that the superconducting state in Sr(2)RuO(4) emerges from a surrounding Fermi-liquid metallic state. Using muon spin relaxation and magnetic susceptibility measurements, we demonstrate here that (Sr,Ca)(2)RuO(4) has a ground state with static magnetic order over nearly the entire range of (Ca, Sr) substitution, with spin-glass behaviour in Sr(1.5)Ca(0.5)RuO(4) and Ca(1.5)Sr(0.5)RuO(4). The resulting new magnetic phase diagram establishes the proximity of superconductivity in Sr(2)RuO(4) to competing static magnetic order.

Single dose topical corticosteroid inhibits IL-5 and IL-13 in nasal lavage following grass pollen challenge.

BACKGROUND: Nasal lavage is a noninvasive method of obtaining inflammatory exudates following nasal allergen challenge (NAC), and permits cells and released mediators to be evaluated. OBJECTIVE: To determine the effects of a single dose of topical steroid on eosinophils and levels of chemokines and cytokines in nasal lavage fluid following NAC in patients with allergic rhinitis. METHODS: Patients with grass pollen seasonal allergic rhinitis (n = 32) out of the allergy season received either nasal budesonide (100 microg per nostril) or matched placebo before allergen challenge in a double blind two-way crossover design. A semi-automated mixed bead array system was employed to measure multiple chemokines and cytokines in small volumes (50 microl) of nasal lavage supernatants. RESULTS: Following NAC there was a rapid onset of nasal symptoms together with nasal eosinophilia, and the appearance of IL-5 and IL-13 in lavages between 4 and 8 h. Elevated levels of eotaxin, RANTES, IL-8 and MCP-1 were also detected following allergen challenge. A single dose of nasal budesonide caused a decrease in symptoms (P < 0.05) and nasal eosinophils (P < 0.05) with selective abrogation of IL-5 and IL-13 responses (P < 0.05), but a lack of effect on levels of eotaxin, RANTES, IL-8 and MCP-1. CONCLUSION: This study suggests that a single dose of nasal steroid has the capacity to selectively abolish IL-5 and IL-13 responses following NAC. This model should be convenient for testing novel anti-inflammatory and immunoregulatory agents intended for the treatment of allergic rhinitis.

Topical corticosteroid inhibits interleukin-4, -5 and -13 in nasal secretions following allergen challenge.

BACKGROUND: Cytokines and chemokines produced by allergen-reactive T-helper type 2 (Th2) cells may be pivotal to the pathophysiology of allergic disorders. OBJECTIVE: This study was performed to assess the effect of 7 days of topical corticosteroid on nasal allergen challenge (NAC) in terms of eosinophils, cytokines and chemokines obtained by nasal lavage and filter paper methods. METHODS: Patients with grass pollen seasonal-allergic rhinitis (n = 13) out of season received nasal challenge following matched placebo (twice daily into each nostril for 7 days) and fluticasone propionate (100 microg twice daily into each nostril for 7 days). Chemokine and cytokine levels were analysed using a sensitive automated bead immunoassay system at intervals up to 8 h after NAC. RESULTS: Levels of cytokines and chemokines from filter paper were generally higher than from nasal lavage. Fluticasone propionate caused a reduction in symptoms, total leukocyte counts and eosinophils, and abrogation of IL-4, IL-5, IL-6 and IL-13 responses in the filter paper taken in the late phase (P < 0.05 for IL-4 and IL-13, P < 0.01 for IL-5 and IL-6). Levels of chemokines (eotaxin, RANTES, MCP-1, MIP-1alpha, IL-8 and IP-10) were also reduced in the late phase (P < 0.01 at 8 h). However, levels of IL-2, IL-3, IL-7, IL-12 (p40 and p70), -15, TNF-alpha, IFN-gamma and GM-CSF were not affected. CONCLUSION: Fluticasone propionate has selective inhibitory effects on Th2 cytokine synthesis following nasal challenge, while also decreasing release of chemokines, but not affecting levels of Th1 cytokines.

Evidence for sensory nerve involvement in cutaneous reactive hyperemia in humans.

To study the involvement of local sensory nerves in reactive hyperemia, laser-Doppler measurements of skin blood flow were recorded in locally anesthetized and untreated forearm sites in eight volunteers after 90, 180, and 360 seconds of arrested forearm blood flow. The reactive hyperemia increased in magnitude and duration in response to increasing occlusion periods. However, maximum postocclusion flows in the untreated site of 31 +/- 5%, 38 +/- 6%, and 49 +/- 5% (mean +/- SEM) flux were significantly greater than the 14 +/- 3% (P < .005), 20 +/- 4% (P < .005), and 25 +/- 5% (P < .001) flux seen in the anesthetized sites. The duration of the hyperemia was also shortened from 139 +/- 26 seconds in the untreated site to 61 +/- 17 seconds (after the 360-second occlusion, P < .02) in the anesthetized sites. The anesthesia did not alter the increase in local blood flow induced by intradermally injected calcitonin gene-related peptide. Topically applied capsaicin induced a localized increase in blood flow that was unaffected by anesthesia and a surrounding flare that was abolished by the treatment. The results show that local anesthesia can significantly inhibit reactive hyperemia by a mechanism that does not alter the vasodilation induced by exogenous calcitonin gene-related peptide or the localized capsaicin-induced release of vasodilators from sensory nerves. Indomethacin was also found to be effective in suppressing reactive hyperemia. The evidence suggests that postocclusion reactive hyperemia in human forearm skin is mediated by a local reflex involving sensory nerves and a cyclooxygenase product, probably a vasodilator prostaglandin.

In vivo and in vitro effects of endotoxin on vascular responsiveness to norepinephrine and signal transduction in the rat.

We investigated, after in vitro and in vivo exposure to gram-negative endotoxin, the altered responsiveness of rat aortic smooth muscle to catecholamines. Two hour exposure of aortic rings from normal rats to 100 ng/ml of Escherichia coli 0111:B4 endotoxin in vitro in an artificial medium supplemented with 5% fetal calf serum at 37 degrees C did not effect the basal and norepinephrine (NE)-stimulated (10 microM, 1 hr, 37 degrees C) phosphoinositide (PI) hydrolysis and isometric contractions induced by graded doses (1 nM to 10.0 microM) of NE. Increasing the incubation time with endotoxin to 18 hr did not alter the basal PI hydrolysis but significantly (P less than 0.05) decreased the NE-induced PI hydrolysis (30% inhibition) and contractile sensitivity to NE (increase of EC50 from 20.0 +/- 3.8 to 156.4 +/- 46.7 nM). Qualitatively similar results were obtained in experiments where rats were injected intravenously with buffer or an LD50 dose (10 mg/kg) of endotoxin. In these ex vivo measurements, only an 18 hr exposure to endotoxin caused significant (P less than 0.001) decreases in basal (58% inhibition) and NE-stimulated (75% inhibition) PI hydrolysis and in NE-induced isometric contractions (increase of EC50 from 11.0 +/- 3.3 to 664.1 +/- 280.0 nM). The results show that the endotoxin-induced hyporeactivity to alpha 1-adrenergic receptor stimulation 1) is markedly dependent on the length of endotoxin exposure, 2) does not require (although may be enhanced by) contact with blood cells and plasma, and 3) is paralleled by a decrease in both basal and NE-stimulated PI hydrolysis.(ABSTRACT TRUNCATED AT 250 WORDS)