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941.
Platelet activation in patients with obstructive sleep apnea syndrome and effects of nasal-continuous positive airway pressure 总被引:3,自引:0,他引:3
Shimizu M Kamio K Haida M Ono Y Miyachi H Yamamoto M Shinohara Y Ando Y 《The Tokai journal of experimental and clinical medicine》2002,27(4):107-112
OBJECTIVE: Our study was undertaken to determine whether increased platelet activation occurs in patients with obstructive sleep apnea syndrome (OSAS) and whether a therapy with nasal-continuous positive airway pressure (N-CPAP) alters this activation. METHODS: We measured the positive rate of activated platelets using activation-dependent monoclonal antibodies (MoAb) and flow cytometry in whole blood from 94 patients with OSAS, and from 31 age-matched controls. Thrombotic vascular diseases were surveyed as a background of alternative of platelet activation. RESULTS: The positive rate for activated platelets was significantly higher in patients with OSAS ( PAC1 52.6 +/- 22.9 %, CD62P 6.8 +/- 7.1%, mean +/- SD), as compared with healthy control subjects ( PAC1 16.7 +/- 8.6 %, CD62P 0.7 +/- 0.5 %, p < 0.001). The activation indexes were significantly reduced after 1 month with N-CPAP treatment as a whole (PAC1; from 52.6 +/- 22.9 to 44.2 +/- 22.4, p < 0.05, CD62P; from 6.8 +/- 7.1 to 5.3 +/- 5.5, p < 0.05). In nearly 60 % of patients, platelets activation remained high despite significant improvement of sleep apnea-episodes after N-CPAP. These patients had significantly higher incidence of previous myocardial infarction and/or cerebral infarction and abnormalities of head MRI and carotid sonograpy; indicating that the platelet activation appears to be induced by existing atheroma plaque and not by sympathetic activity in OSAS. CONCLUSION: In conclusion, patients with OSAS have increased percentages of activated platelets as assessed by flow cytometrical analysis of activation dependent surface markers, and were divided into two groups, one group with response to N-CPAP treatment in the reduction of platelet activation and the other without. One possible reason of no response to N-CPAP treatment in the reduction of platelet activation was suggested to be thrombotic diseases. 相似文献
942.
Kominami G Agou T Kanda A Ohno M 《Journal of pharmaceutical and biomedical analysis》2002,30(3):733-738
Immunoassay for recombinant methioninase (rMETase), an anti-cancer agent, in biological sample was developed. Antisera were produced by immunizing rabbits with rMETase. The antisera were evaluated using radioiodine-labeled rMETase and good antisera for sensitive immunoassay were obtained. Horseradish peroxidase (HRP) was coupled to reduced IgG of K232 antiserum through bridging agent, N-(epsilon -maleimidocaproyloxy) sulfosuccinimide ester (sulfo-EMCS), to prepare enzyme-labeled antibody. IgG fraction of K231 antiserum was immobilized on microplate well. Two-site sandwich immunoenzymometric assay (IEMA) was developed using these antibodies and had good standard curve between 0.4 and 12 ng per well. For determination of rMETase in mouse plasma, sample was diluted 100-fold with dilution buffer containing protease inhibitors, because about 10% of rMETase immunoreactivity was lost for 2 h at room temperature. rMETase in mouse plasma could be determined by the proposed method in the range of 0.5-8 microg/ml and the method was validated. This novel IEMA, in substitution for the measurement of its enzyme activity, should be very useful not only for preclinical studies of rMETase but also for the clinical studies. 相似文献
943.
Stimulation of beta(3)-adrenoceptors causes phosphorylation of p38 mitogen-activated protein kinase via a stimulatory G protein-dependent pathway in 3T3-L1 adipocytes
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1. This study deals with phosphorylation and activation of p38 mitogen-activated protein kinase (MAPK) via beta(3)-adrenoceptor (AR) and the signal transduction pathway in 3T3-L1 adipocytes. 2. beta(3)-AR agonist BRL37344A (10 nM) caused phosphorylation and activation of p38 MAPK in 3T3-L1 adipocytes but not in fibroblasts. BRL37344A and also the other beta(3)-AR agonists, CGP12177A and SR58611A, caused p38 MAPK phosphorylation in dose-dependent manners. 3. The p38 MAPK phosphorylations by BRL37344A (10 nM), CGP12177A (100 nM), and SR58611A (10 nM) were not antagonized by beta(1)- and beta(2)-ARs antagonist 1-propranolol (100 nM) but blocked by beta(3)-AR antagonist SR59230A (10 microM), suggesting the phosphorylation was caused via beta(3)-AR. 4. The phosphorylations of p38 MAPK were completely abolished by treatment with cholera toxin (CTX) but not pertussis toxin (100 ng ml(-1), 24 h). Activation of Gs by CTX (100 ng ml(-1)) and adenylyl cyclase by forskolin mimicked p38 MAPK phosphorylation. 5. p38 MAPK phosphorylation by BRL37344A was reduced to almost 50% by cyclic AMP-dependent protein kinase (PKA) inhibitors such as H89 (10 microM) and PKI (10 microM). A src-family tyrosine kinases inhibitor PP2 (1 microM) also halved the p38 MAPK phosphorylation. Combined use of H89 (10 microM) and PP2 (10 microM) did not bring about further inhibition. 6. These results suggest that beta(3)-AR caused phosphorylation of p38 MAPK via Gs protein and partly through a pathway involving PKA and src-family kinase(s), although the contribution of the unidentified pathway remains to be clarified. 相似文献
944.
945.
Surgical operations often induce acute hyperglycemia, which is known to affect endothelial functions. In this study, we examined the effects of propofol, a commonly used general anaesthetic, on bovine aortic endothelial cell (BAEC) dysfunction induced by glucose overload. 2 D-glucose overload (23 mM) induced an accumulation of superoxide anion (O2-), assessed by MCLA chemiluminescence, to a similar extent as that generated by 233 microU ml(-1) xanthine oxidase (XO) and 100 micro M xanthine. Propofol inhibited this accumulation with an IC50 of 0.21 micro M, whereas much higher concentrations of propofol were required to scavenge O2- generated by 250 microU ml(-1) XO and 100 microM xanthine (IC50: 13.5 micro M). 3 D-glucose overload attenuated ATP-induced NO production which was detected using diaminofluorescence-2 (DAF-2). The inhibition was reversed by propofol with an EC50 of 0.60 microM. In contrast, inhibitions caused by xanthine/XO were not altered by propofol (1 microM). 4 D-glucose overload suppressed ATP-induced Ca2+ oscillations and capacitative Ca2+ entry (CCE), which were both restored by superoxide dismutase, indicating that O2- was responsible. Propofol restored these attenuated Ca2+ oscillations and CCE with EC50 of 0.31 and 1.0 microM, respectively. 5 D-glucose overload (23 mM) increased the intracellular glucose concentration 4 fold, compared with cells exposed to 5.75 mM glucose, and 1 micro M propofol reduced this increase to 2.8 fold. 6 We conclude from these results that anaesthetic concentrations of propofol prevent the impairment of Ca2+-dependent NO production in BAEC induced by glucose overload. This effect is mainly due to the reduction of O2- accumulation, and involves, at least in part, the inhibition of cellular glucose uptake. 相似文献
946.
Miura S Fujino M Tanigawa H Matsuo Y Saku K 《Nihon yakurigaku zasshi. Folia pharmacologica Japonica》2002,120(1):104P-105P
BACKGROUND: Endothelial cells (ECs) are believed to be critical cellular elements responsible for postnatal angiogenesis. Vascular endothelial growth factor (VEGF) stimulates angiogenesis via the activation of KDR/Flk-1 receptor, which is mainly expressed in ECs. Transactivation of KDR/Flk-1 receptor by bradykinin (BK) B2 receptor contributes to the activation of endothelial nitric-oxide (NO) synthase. Therefore, we examined whether transactivation by BK induced angiogenesis. METHODS AND RESULTS: We developed an in vitro model of human coronary artery ECs (HCECs) tube formation on a matrix gel. We demonstrated that BK dose-dependently induced tube formation. Although a lower concentration of BK did not induce tube formation, the combination of a lower concentration of BK and VEGF did. These effects blocked specific inhibitors of VEGF receptor tyrosine kinases (Tki) and NO synthase. In addition, BK induced the tyrosine phosphorylation of KDR/FlK-1 receptor (transactivation), as did VEGF itself. This transactivation was also blocked by Tki. CONCLUSIONS: Transactivation of KDR/Flk-1 by BK through B2 receptor is a potent signaling in angiogenic phenotype in HCECs. 相似文献
947.
Kinoshita M Baba K Nagayasu A Yamabe K Shimooka T Takeichi Y Azuma M Houchi H Minakuchi K 《Journal of pharmaceutical sciences》2002,91(2):362-370
The aim of the present study was to improve the solubility and oral bioavailability of a poorly water-soluble drug, 3-bis(4-methoxyphenyl) methylene-2-indolinone (TAS-301), by its melt-adsorption on a porous calcium silicate, Florite RE (FLR), without any solvents. The melt-adsorbed products were prepared by two methods: the small-scale batch method and the twin screw extruder method. The drug was melted and adsorbed on FLR (i.e., "melt-adsorption"), above its melting point. Crystallinity of the drug in the melt-adsorbed product was estimated by differential scanning calorimetry (DSC) and powder X-ray diffraction analysis. The dissolution test was conducted by the JP XIII paddle method. Oral absorption of the melt-adsorbed product was studied in fasted and fed dogs. The melt-adsorbed products prepared by the two methods were in powder forms. The drug existed in an amorphous state in the product and hardly recrystallized even after storing at a stressed condition (60 degrees C/80% RH for 3 days). The TAS-301 dissolution rate from the melt-adsorbed product was markedly enhanced compared with drug crystals. The area under the plasma concentration-time curve (AUC) and peak concentration (C(max)) values of the drug after dosing the melt-adsorbed product were significantly greater than those after dosing the drug crystals. The solubility and bioavailability of TAS-301 were improved by its melt-adsorption on FLR. The present findings suggest melt-adsorption is a useful technique for improving solubility and bioavailability of poorly water-soluble drugs. 相似文献
948.
949.
Takeyoshi M Sawaki M Noda S Muroi T Yamasaki K 《Reproductive toxicology (Elmsford, N.Y.)》2002,16(4):367-369
The immature rat uterotrophic assay has been proposed as a screening test method for detecting estrogenic and antiestrogenic chemicals. Although the immature rat uterotrophic assay is advantageous because the test animals are not traumatized by the ovariectomizing process, the effect of endogenous estrogen on ovarian and uterine weight in the immature animals that are used in immature rat uterotrophic assay has not received much attention. In this study, 19-day-old rats were treated with antide, a gonadotropin-releasing hormone antagonist, antide, to block gonadal production of endogenous estrogen. Uterine and ovarian weights of the antide-treated animals were markedly lower than those of control animals. This finding suggests that endogenous gonadal estrogen may already be acting on the uterus and ovaries in immature rats. Blocking endogenous estrogen with a gonadotropin-releasing hormone antagonist may enhance the sensitivity of the immature rat uterotrophic assay; however, the possibility that this protocol may interfere with the ability of the immature rat uterotrophic assay to detect centrally-mediated effects can not be discounted. 相似文献
950.
Sakaguchi M Ikeda Y Kido T Yuzurihara M Kase Y Yamamoto M Ishige A Sasaki H 《Biological & pharmaceutical bulletin》2002,25(12):1562-1565
The pharmacological characteristics of Ryokan-kyomi-shinge-nin-to (RKS), a traditional oriental herbal (Kampo) medicine which has been used for the treatment of allergic asthma and rhinitis, were investigated. The number of sneezes by actively sensitized mice after a topical antigen challenge was significantly reduced by pretreatment with RKS (300 and 1000 mg/kg, p.o.). Although RKS did not inhibit the antigen-induced histamine release from rat peritoneal exudate cells (PEC), it significantly inhibited an increase in vascular permeability induced by histamine and serotonin. These results suggest that RKS has antiallergic activity in animals, and the functional antagonism of a histamine response may be one of the mechanisms of its effect. In addition, RKS prevented histamine hypersensitivity in actively sensitized mice. Because RKS did not affect sleeping time induced by pentobarbital in mice and did not inhibit gastric emptying in rats, the drug appears to be useful for treating allergic patients suffering from classical antihistamines side effects such as stomach discomfort or relative drowsiness. 相似文献