The purpose of this study was to assess the time of onset of action of acrivastine in suppressing the wheal response to histamine (10 mg/ml) and allergen (10000 and 100000 BU/ml) in the skin prick test. Ten subjects with a well-documented allergy to pollen received single doses of 8 mg of acrivastine and placebo according to a randomized, double-blind, placebo-controlled, crossover treatment design. Duplicate skin prick tests were performed 0, 15, 20, 25, 30, and 60 min after medication. The results demonstrated a statistically significant suppression of the wheal reactions 15–20 min after medication, depending on the reaction producers used. The sum of all three producers showed a statistically significant effect on the wheal reaction 15 min after medication. The upper 95% confidence limit for time lag from dosing of acrivastine until reduction from placebo level commences was 6.5 min. The study substantiates that orally administered acrivastine has a rapid onset of action in the skin of allergic subjects. The results indicate that allergen SPT is a more sensitive tool for studying antihistaminergic activity than histamine SPT. 相似文献
Effector T cells fall into two subpopulations based on cytokine-secretion. Type 1 cells secrete IFN-gamma, whereas type 2 cells secrete IL-4, IL-10, and GM-CSF. NKT cells represent a third subpopulation that secretes similar cytokines and have been associated with immunoregulation. Using the TS/A adenocarcinoma, we assessed the phenotype and kinetics of tumor-infiltrating lymphocytes (TIL) in mice challenged subcutaneously in the mammary region. Flow cytometric analysis shows that T cells do not infiltrate the primary tumor site until days 7-14 following tumor challenge. Both CD4 and CD8 TILs were predominantly CD44(High) and expressed CD25, CD69, and CD95 cell surface activation markers. Activated CD4/CD44(High) TIL numbers reached peak levels at day 21 that precipitously decreased by day 28 whereas corresponding CD8 cell numbers progressively increased, however, at lower levels and with later kinetics. Intracellular cytokine staining showed that greater numbers of IL-4-producing Th2 cells were elicited and with earlier kinetics than that of IFN-gamma-producing Th1 cells. T cells co-expressing DX5 (CD3(+)/DX5(+)) emerged (>21 days), suggesting a recruitment of NK-like T cells at later stages of tumor progression. Moreover, tumors selectively up-regulated TGF-beta, MIF, and IP-10 gene expression at times as early as day 4, with peak levels at day 7 in vivo. Such gene expression remained elevated and correlated with a continued progression in tumor growth suggesting that preferential effector cell recruitment and production of select factors during different stages of tumor maturation may aid in regulating effective endogenous antitumor responses in progressive breast cancer. 相似文献
We have established the content and molecular species of immunoreactive β-endorphin (ir-β-END) and immunoreactive N-acetyl-endorphin (ir-Nac-END) in rat neurointermediate lobe by specific radioimmunoassay (RIA) and high-performance liquid chromatography after chronic administration of dopamine (DA) agonists and antagonists. The DA agonist, bromocriptine, reduces tissue levels of all major immunoreactive species, in particular the C-terminally shortened N-acetylated forms. The DA antagonist, haloperidol, proportionally increases all immunoreactive forms, except Nac-β-END1–27, thus altering the relative abundance of this species. These data indicate that DA is involved in the control of both tissue levels and processing of β-END-like peptides in the rat neurointermediate lobe. 相似文献
We have previously demonstrated by immunohistochemistry that mucosal expression of beta 2 integrins was enhanced in Crohn's disease and ulcerative colitis as compared to normal controls. We aimed, therefore, to determine whether there was a corresponding alteration in the expression of CD11a/CD18 (LFA-1), the primary lymphocyte beta 2 integrin, among the principal subsets of lamina propria lymphocytes (LPLs). Accordingly, LPLs were extracted from surgical resection specimens derived from patients with Crohn's colitis, ulcerative colitis, and from noninflamed controls. Following immunofluorescent staining, three-color flow-cytometry analysis identified LPLs on the basis of CD45 side scatter gating, which in turn, were further subdivided into CD4(+), CD8(+), and CD19(+) cells to account for the predominant T and B cells in the lamina propria. Expression patterns of CD11a, the alpha-subunit of LFA-1; CD18, the beta-subunit of LFA-1; and alpha d, a novel alpha-subunit of the beta 2 integrin family were assessed for each of these lymphocyte subsets. In Crohn's disease and ulcerative colitis there was an increased mean percentage expression of CD4(+) cells and CD11a(+) cells compared with noninflamed controls. CD11a was more likely to be expressed on CD4(+) cells in both Crohn's disease and ulcerative colitis and compared with controls and less expressed on CD19(+) cells. It is likely that an influx of CD4(+)11a(+) cells into the lamina propria accounted for these changes. These results suggest that although currently there is great interest in harnessing alpha 4 beta 7 in treatment of inflammatory bowel disease, further consideration should be given to the role of CD11a in these disease states. 相似文献
Japanese patients with rheumatoid arthritis (RA) were observed to have a statistical association with HLA-DR4, MT3. Strong association between the clinical severity of RA and HLA was also observed. Male patients had a stronger association with HLA than female patients. Males are more resistant to RA than females. This suggested that the threshold of liability for RA is higher in males than in females. Japanese patients with RA with systemic vasculitis were negative for HLA-Bw44 and had antilymphocytotoxic autoantibody, indicating that RA with systemic vasculitis is different in etiology from RA without systemic vasculitis. 相似文献
Objectives: Gouty arthritis is caused by the deposition of monosodium urate (MSU) crystals in joints, which is associated with the rise of serum urate content. This study aims to investigate the therapeutic effect of Madecassoside on gouty arthritis and hyperuricemia.
Methods: DBA/1 mice were intradermally injected with MSU to stimulate joint inflammation or intraperitoneally injected with MSU to trigger peritonitis. Moreover, ICR mice were exposed to potassium oxonate to stimulate hyperuricemia.
Results: Madecassoside repressed MSU-triggered pad swelling, joint 99mTc uptake, and joint inflammation in DBA/1 mice with gouty arthritis. Neutrophil infiltration and IL-1β & IL-6 & MCP-1 secretion was also alleviated in lavage fluids from DBA/1 mice with peritonitis due to Madecassoside treatment. Furthermore, Madecassoside decreased MSU-induced neutrophil cytosolic factor 1, caspase-1 and NLRP3 expression in mice with peritoneal inflammation. In hyperuricemic mice, Madecassoside improved renal dysfunction. Serum uric acid, BUN, and creatinine were down-regulated by Madecassoside.
Conclusion: These findings indicate that Madecassoside has potential to ameliorate inflammation in both acute gouty arthritis model and peritonitis model, probably via regulating IL-1β and NLRP3 expression.
Practical point: Madecassoside also exhibited a urate-lowering effect and a renal protective effect in hyperuricemic mice. 相似文献
The effects of verapamil upon cerebrospinal fluid pressure (CSFP) were studied in twenty surgical patients without intracranial pathology who were divided into two groups of ten patients each: verapamil 0.075mg·kg–1 was given in group 1 and 0.15mg·kg–1 was given in group 2. A spinal needle was inserted into the subarachnoid space to permit continuous measurement of CSFP. Intravenous verapamil as a bolus produced a statistically significant increase in CSFP: from 6.0 ± 3.5 (mean ± SD) to 10.5 ± 4.3mmHg in group 1 (P < 0.01), and from 6.2 ± 3.1 to 12.6 ± 3.8mmHg in group 2 (P < 0.01). CSFP after verapamil attained its maximum in 0.5–1.5min, then gradually returned to control levels. Changes in CSFP were always associated with statistically significant decreases in arterial blood pressure and cerebral perfusion pressure, while the heart rate showed variable changes. It is concluded that a clinical dose of verapamil showed variable changes. It is concluded that a clinical dose of verapamil (0.075–0.15mg·kg–1) has no neurological side effects in patients without intracranial hypertension. However, it must be emphasized that verapamil may increase CSFP to undesirable levels and should be avoided in patients with compromised intracranial compliance.(Nishikawa T, Namiki A: The effects of verapamil on cerebrospinal fluid pressure in surgical patients. J Anesth 1: 132–136, 1987) 相似文献