Chronic headaches are difficult to treat and represent the biggest challenge in headache centres. Mirtazapine has a prophylactic and ibuprofen an acute effect in tension-type headache. Combination therapy may increase efficacy and lower side effects. We aimed to evaluate the prophylactic effect of a combination of low-dose mirtazapine and ibuprofen in chronic tension-type headache. Ninety-three patients were included in the double-blind, placebo-controlled, parallel trial. Following a 4-week run-in period they were randomized to four groups for treatment with a combination of mirtazapine 4.5 mg and ibuprofen 400 mg, placebo, mirtazapine 4.5 mg or ibuprofen 400 mg daily for 8 weeks. Eighty-four patients completed the study. The primary efficacy parameter, change in area under the headache curve from run-in to the last 4 weeks of treatment, did not differ between combination therapy (190) and placebo (219), P = 0.85. Explanatory analyses revealed worsening of headache already in the third week of treatment with ibuprofen alone. In conclusion, the combination of low-dose mirtazapine and ibuprofen is not effective for the treatment of chronic tension-type headache. Moreover, the study suggests that daily intake of ibuprofen worsens headache already after few weeks in chronic tension-type headache. 相似文献
Administration of cholinotoxin etylcholine aziridinium (AF64A) into the brain selectively induces nonrever-sible cholinergic deficit. Wistar rats were injected intracerebroventricularly bilaterally with AF64A at doses of 1–3 nmol/ventricle. 28 days later the number of neurons survived was counted in dorsolateral, intermediate and medial groups of cells of the medial septum. AF64A induced a decrease in neuronal density and expression of cholineacetyl transferase at all doses used as well as in all regions studied. Brain sections were also stained for NADPH-diaphorase representing neuronal NO-synthase. Effects of AF64A on NADPH-diaphorase expression depended on the region studied. The number of NADPH-diaphorase-positive cells increased in the medial cellular group where more cholineacetly transferase-positive cells survived. In contrast, decrease in NADPH-diaphorase expression in the dorsolateral group of cells coincided with low level of cholineacetyltransferase-po-sitive neurons. The data presented suggest that in the AF64A-dependent model of neurodegeneration NO may play a neuroprotective function. 相似文献
HYPOTHESIS: Based on recent findings on the association between vascular risk factors and hippocampal atrophy, we hypothesized that hypertension and diabetes mellitus (DM) are associated with medial temporal lobe atrophy (MTA) in subjects without disability, independent of the severity of white matter hyperintensities. METHODS: In the Leukoaraiosis And DISability in the elderly (LADIS) study, we investigated the relationships between DM, hypertension, blood pressure and MTA in 582 subjects, stratified by white matter hyperintensity severity, using multinomial logistic regression. MTA was visually scored for the left and right medial temporal lobe (score 0-4), and meaned. RESULTS: Mean age was 73.5 years (sd 5.1), 54% was female. Of the subjects, 15% had DM, and 70% had a history of hypertension. The likelihood of having MTA score 3 was significantly higher in subjects with DM (OR 2.9; 95% CI: 1.1-7.8) compared with an MTA score of 0 (no atrophy). The odds ratio for MTA score 2 was not significantly increased (OR 1.8; CI: 0.9-4). Systolic and diastolic blood pressure and a history of hypertension were not associated with MTA. There was no interaction between DM and hypertension. Stratification on white matter hyperintensities (WMH) did not alter the associations. CONCLUSION: Our study strengthens the observation that MTA is associated with DM, independently of the amount of small vessel disease as reflected by WMH. 相似文献
Degranulating mast cells are increased in the airway smooth muscle (ASM) of asthmatics, where they may influence ASM function. The aim of the present study was to determine whether histamine and tryptase modulate ASM cell granulocyte-macrophage colony-stimulating factor (GM-CSF) and RANTES (regulated on activation, normal T-cell expressed and secreted) release and also to examine which receptors are involved in this release. Confluent, quiescent ASM cells from asthmatic and nonasthmatic donors were treated with histamine (1 microM-100 microM) with and without histamine receptor antagonist pre-treatment, or the protease-activated receptor (PAR)-2 agonists tryptase (0.5-5 nM) and SLIGKV (100 and 400 microM). The cells were then stimulated with interleukin (IL)-1beta and/or tumour necrosis factor (TNF)-alpha (10 ng.mL(-1)) or left unstimulated for 24 h. Release of GM-CSF and RANTES was determined by ELISA and prostaglandin (PG)E(2) measured by enzyme immunoassay. Neither histamine nor tryptase induced ASM GM-CSF or RANTES secretion. However, histamine increased IL-1beta-induced GM-CSF release and markedly reduced TNF-alpha-induced RANTES release by both asthmatic and nonasthmatic cells to a similar extent, but did not modulate PGE(2) release. All changes involved activation of the histamine H1 receptor as they were partially or fully blocked by chlorpheniramine, but not ranitidine. Tryptase, via its proteolytic activity, also potentiated GM-CSF, but not RANTES, release from asthmatic and nonasthmatic ASM cells induced by both cytokines. PAR-2 involvement in the tryptase potentiation was unlikely because SLIGKV had no effect. In conclusion, mast cells, through histamine and tryptase, may locally modulate airway smooth muscle-induced inflammation in asthma. 相似文献
Background: Developmental differences in short- and long-term responses to pain, especially surgical pain, have received minimal attention. The purpose of the present study was to examine postoperative responses in rats of developmental ages paralleling the infant to young adult human.
Methods: The withdrawal threshold to von Frey filament testing and withdrawal latency to hind-paw radiant heating were determined before and for various times after hind-paw incision in rats 2, 4, and 16 weeks of age. Control rats of these ages were observed serially without surgery.
Results: In control animals, younger rats were more sensitive to mechanical stimulation and less sensitive to thermal stimulation. Paw incision resulted in similar changes to both types of stimulation in all age groups, peaking 4 h after surgery. However, the return to normal sensitivity to mechanical stimulation, as measured by return of threshold to 80% of normal, occurred more quickly in 2-week-old than in 4- and 16-week-old animals. In contrast, there was no age difference for time to return to normal sensitivity to thermal stimulation after surgery. 相似文献