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51.
Characteristics of the antihistamine effect of TAK-427, a novel imidazopyridazine derivative 总被引:1,自引:0,他引:1
S. Fukuda K. Midoro M. Yamasaki M. Gyoten Y. Kawano H. Fukui Y. Ashida H. Nagaya 《Inflammation research》2003,52(5):206-214
OBJECTIVE AND DESIGN: The characteristics of the antihistamine effect of the new antiallergic compound TAK-427 were investigated. MATERIALS AND METHODS: In vitro binding assay of [(3)H] pyrilamine was performed using recombinant human histamine H(1) receptors (rhH(1)R). In vivo studies were performed in male ICR mice or Hartley guinea pigs. Drugs were administered orally 1 h before examinations. Determinations were made of histamine-induced skin reaction, ex vivo measured radioligand binding to brain and lung H(1) receptors, pentobarbital-induced sleeping time, passive cutaneous anaphylaxis (PCA) reaction, and antigen-induced itch-scratch responses (ISRs). RESULTS: TAK-427 inhibited ligand binding to rhH(1)R with an IC(50) value of 17.3 nmol/l. TAK-427 inhibited histamine-induced skin reactions in guinea pigs and mice with an ID(50) value of 0.884 and 0.450 mg/kg, p.o., respectively; significant inhibition associated with 10 mg/kg of TAK-427 was still observed 24 h after dosing in guinea pigs. TAK-427 showed as high selectivity for peripheral H(1) receptors as terfenadine and epinastine did, which was evaluated by ex vivo measured radioligand binding. Even at 300 mg/kg, TAK-427 did not affect pentobarbital-induced sleeping time in mice. TAK-427 significantly inhibited PCA in mice and guinea pigs, and also inhibited antigen-induced ISRs in guinea pigs. CONCLUSIONS: These results suggest that TAK-427 may have a long-lasting antihistamine activity with minimum sedative side effect and suppress acute phase allergic reactions. 相似文献
52.
The kinetics of IgE-mediated release of serotonin from passively sensitized rat mast cellsin vitro was studied by stopping14C-serotonin release with the application of formaldehyde fixative or ice-cold mast cell medium (MCM). Antigen dose-release curves of14C-serotonin and/or histamine were comparable when mediator release was terminated with either formaldehyde at a final concentration of 1% or ice-cold MCM 15 min after antigen challenge. However, the kinetic study of immunological mediator release stopped by formaldehyde showed that the addition of antigen resulted in a progressive increase of released14C-serotonin for 7 min, the release curve being sigmoidal, whereas the application of ice-cold MCM artificially enhanced14C-serotonin and histamine release in the first 2 min. The results suggest that stopping IgE-mediated release of14C-serotonin with formaldehyde is a simple, rapid and accurate method of studying the kinetics of mediator release from mast cells. 相似文献
53.
A. M. Albisser Y. Yamasaki H. Broekhuyse J. Tiran 《Annals of biomedical engineering》1980,8(4-6):539-557
A hypercomplex circulation and organs model of glucose and insulin dynamics is presented. The model is based on physiological
parameters, incorporating blood and plasma flow rates, circulatory paths, intra- and extravascular glucose and insulin spaces,
as well as the specific organs and tissues involved both with insulin disappearance and with glucose production or uptake.
Its simulations readily lend themselves to physiological interpretation. To explore its validity, the model was assigned parameters
typical of a 12 kg dog and was arranged to accept known glucose and insulin infusions from two different experiments on pancreatectomized
diabetic animals. It predicted the observed glucose and insulin concentrations as well as uptake rates for both moieties in
the individual organs and tissues. This confirmed the ability of the model to predict with consistency the group mean outcomes
of both experiments when differing routes (portal or peripheral) of infusion were applied. Excellent agreement was achieved
for the studies. The model isolates glucose uptake in the periphery, the liver, the brain, and the gut and allows a direct
comparison of glucose disposal along various routes. Thus, the total amount of glucose uptake by peripheral, insulin-dependent
tissues is directly calculated to be 30% of an intravenous glucose load, with peripheral infusion, which is higher than that
with portal infusion (18%).
This investigation was conducted as a project of the Artificial Pancreas Programme and is supported in part by a grant MA5767
from the Medical Research Council of Canada and a negotiated contract No. NO1-AM-9-2201 from The National Institutes of Health,
Bethesda, Maryland. 相似文献
54.
Cardiac ankyrin repeat protein (CARP), which is structurally characterized by the presence of four ankyrin repeat motifs in its central region, is believed to be localized in the nucleus and to participate in the regulation of cardiac-specific gene expression in cardiomyocytes. However, we recently found that CARP was induced in skeletal muscle by denervation, leading us to speculate that CARP may be induced under some pathological conditions. In the present study, we immunohistochemically analyzed the expression of CARP in 11 cases of spinal muscular atrophy (SMA) and 14 cases of congenital myopathy. In SMA, CARP was expressed selectively in severely atrophic myofibers, suggesting that CARP expression may reflect the status of muscle atrophy. Furthermore, in the congenital myopathies, the expression patterns of CARP were distinct among the subtypes, which included nemaline myopathy, myotubular myopathy, central core disease, and congenital fiber type disproportion. Although CARP was preferentially expressed in severely damaged myofibers in nemaline myopathy, it was not detected in central core disease. These findings suggest that immunohistochemical evaluation of CARP may be helpful in the diagnosis of SMA and the congenital myopathies. 相似文献
55.
Suda K Takase M Shiono S Yamasaki S Nobukawa B Kasamaki S Arakawa A Suzuki F 《Histopathology》2002,41(4):351-356
AIMS: To clarify the mechanism of origin of duodenal wall cysts in patients with chronic pancreatitis, developing into duodenal stenosis. METHODS AND RESULTS: Specimens from 12 pancreatoduodenectomized patients with chronic pancreatitis and 51 controls were studied histopathologically and immunohistochemically. Variously shaped cystic lesions, averaging about 15 mm in diameter, were found in the duodenum in six of the 12 patients with chronic pancreatitis, but were not observed in the controls. Each case had an average of two cysts, which were located mainly in the muscularis propria of the duodenum with or without submucosal or extraduodenal-peripancreatic extensions. The inner part of the cyst wall consisted of a moderate rim of granulation tissue, with both myofibroblasts and smooth muscle proliferation in the tissue surrounding the cyst and the submucosal layer of the duodenum, occasionally accompanied by an epithelial lining. A ductal structure in the muscularis propria of the duodenum, possibly a ductal component of ectopic pancreatic tissue, was found in five of the six cases. Some of these structures showed cystic changes. Three of the six patients had accompanying duodenal stenosis. CONCLUSIONS: Duodenal wall cysts occur mainly in the muscularis propria of the duodenum associated with both myofibroblasts and smooth muscle proliferation, and may result in duodenal stenosis. These cysts may be derived from a ductal component of ectopic pancreatic tissue. 相似文献
56.
Masaki Shiota Noriaki Tokuda Takehiro Kanou Humio Yamasaki 《Nippon Ika Daigaku zasshi》2007,74(4):306-308
Although injection-site granulomas caused by leuprorelin acetate have been reported, there have been no reports of granulomas caused by both leuprorelin acetate and goserelin acetate. An 81-year-old man presented with subcutaneous nodules of the abdominal wall and upper arm, where 11.25 mg of leuprorelin acetate had been injected for the treatment of prostate cancer. Because of these nodules, treatment was changed to goserelin acetate. Nevertheless, he presented with another subcutaneous nodule at the injection site. Histological examination showed that these nodules consisted of numerous giant cells that were CD3-positive T lymphocytes and CD68-positive histiocytes associated with granulomatous changes. The granulomas had likely been caused by delayed-type hypersensitivity to leuprorelin acetate injection. The granuloma that formed after goserelin acetate injection might thus have developed owing to the immunogenicity of the previous leuprorelin acetate injections. The patient underwent surgical castration. The present case suggests that both leuprorelin acetate and goserelin acetate can cause injection-site disorders. 相似文献
57.
58.
59.
Fumiyuki Yamasaki Yoshinori Kajiwara Seiji Hama Taro Murakami Toshikazu Hidaka Taiichi Saito Hiroyuki Yoshioka Kazuhiko Sugiyama Kazunori Arita Kaoru Kurisu 《Pathobiology》2007,74(1):22-31
OBJECTIVE: To investigate the mechanism of staurosporine-induced glioma cell death and cell cycle arrest using adenovirus-mediated gene transfection, as well as the function of retinoblastoma (Rb) and genetic instability induced by staurosporine. METHODS: Cell cycle regulation, cell death and nuclear abnormalities induced by staurosporine were examined using an adenovirus vector expressing Rb, p16 or p21 genes in human glioma cell lines. RESULTS: The Rb-defective SF-539 cell line was resistant to staurosporine compared with cell lines expressing intact Rb. SF-539 glioma cells exposed to staurosporine became multinucleated and then died. Multinucleation was prevented in SF-539 cells transfected with the Rb gene, thus decreasing the death rate of these cells. CONCLUSIONS: These results imply that enforced Rb expression protects cells from genomic instability induced by staurosporine regardless of its upstream molecular effects. 相似文献
60.
Hisao Yamaguchi Junya Fukuda Kensuke Baba Hiroshi Takeuchi Keizo Kageyama 《Pathology international》1972,22(3):427-440
The vascular structures in the lymph node and their relation to fluid exchange have been reported in previous communications and it was considered that the morphological changes of the vascular structures were closely correlated with the functional development of lymph nodes as an antibody forming organ. In order to clarify the localization of the given antigen and newly formed antibody in relation to the morphological structure of lymph nodes, the popliteal lymph nodes of rabbits were studied by immuno-fluorescent techniques.
The antibody was found in the pavement arrangement (solid) of reticulum tissue which was formed by the expel of lymphocytes in the cortical mass and by the morphofunctional alterations of the reticulum cells. The given antigen and newly formed antibody were never detected in the follicles throughout the period of this experiment. ACTA PATH. JAP. 22:427–440, 1972. 相似文献
The antibody was found in the pavement arrangement (solid) of reticulum tissue which was formed by the expel of lymphocytes in the cortical mass and by the morphofunctional alterations of the reticulum cells. The given antigen and newly formed antibody were never detected in the follicles throughout the period of this experiment. ACTA PATH. JAP. 22:427–440, 1972. 相似文献