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AD Michel KJ Miller K Lundstr?m GN Buell PP Humphrey 《Canadian Metallurgical Quarterly》1997,51(3):524-532
The rat recombinant P2X4 purinoceptor was expressed in CHO-K1 cells, and binding studies were performed using the radioligand [35S]adenosine-5'-O-(3-thio)triphosphate ([35S]ATPgammaS). In 50 mM Tris/1 mM EDTA assay buffer, pH 7.4 at 4 degrees, [35S]ATPgammaS bound with high affinity to the P2X4 purinoceptor (KD = 0.13 nM, Bmax = 151 pmol/mg of protein). The purinoceptor agonists ATP and 2-methylthioadenosine triphosphate possessed nanomolar affinity for the P2X4 purinoceptor, whereas the antagonist suramin possessed much lower affinity (IC50 = 0.5 mM). Cibacron blue was more potent than suramin but produced a biphasic competition curve, whereas d-tubocurarine potentiated binding at concentrations in excess of 10 microM. The complex effects of cibacron blue and d-tubocurarine seemed to be due to an allosteric interaction with the P2X4 purinoceptor because these compounds affected radioligand dissociation, measured after isotopic dilution with unlabeled ATPgammaS. Cibacron blue (1-100 microM) and d-tubocurarine (0.1-1 mM) produced rapid (10 sec to 5 min) decreases or increases, respectively, in the level of [35S]ATPgammaS binding measured immediately after initiation of the dissociation reaction. However, the subsequent rates of radioligand dissociation were not markedly different from those measured in their absence. Monovalent cations produced similar affects on the P2X4 purinoceptor and, like d-tubocurarine, increased [35S]ATPgammaS binding. The actions of d-tubocurarine and sodium were not additive. The findings from this study indicate that [35S]ATPgammaS can be used to label the P2X4 purinoceptor and suggest that this binding can be enhanced by monovalent cations and d-tubocurarine and may be subject to negative allosteric modulation to varying degrees by different purinoceptor antagonists. 相似文献
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VV Kukharchuk EIu Solov'ev PP Malyshev TA Rozhkova OA Semenova EE Aronskaia 《Canadian Metallurgical Quarterly》1997,69(9):41-45
13 patients aged 39 to 60 years with coronary atherosclerosis confirmed at selective coronary angiography combined with primary hyperlipidemia (phenotypes 2a and 2b) received enduracin in a dose 1500 mg/day. As a result of the treatment total cholesterol (TC) and LDL cholesterol lowered by 10.3 and 13.1%, respectively, whereas HDL cholesterol rose by 15.2%. Half of the patients demonstrated activation of hepatic transaminases, but discontinuation of the drug was not necessary. In 3 out of 4 patients after 2 years of enduracin treatment stabilization of atherosclerosis was observed. Thus, long-term enduracin is able to inhibit progression of atherosclerosis in coronary heart disease patients. 相似文献
86.
BACKGROUND: Supraclinoid carotid aneurysms have traditionally been classified according to their relation to the major carotid branches, but considerable variation exists with respect to site of origin, projection, and relationship to the skull base. Distal internal carotid aneurysms with a superior or medial projection are uncommon vascular lesions, with an unusually high incidence of operative complications. METHODS: Surgical experience with five patients suffering from subarachnoid hemorrhage due to ruptured aneurysms of the dorsomedial wall of the distal internal carotid artery is presented, with emphasis on their angiographic appearance, anatomical features, and operative management. RESULTS: All five patients underwent surgical clipping. Intra-operative rupture occurred in two cases, with avulsion of the aneurysm from the internal carotid artery in both. A third patient experienced recurrent subarachnoid hemorrhage three days after uneventful surgery, due to the clip shearing off of the parent vessel. CONCLUSIONS: Distal internal carotid aneurysms do not conform to the usual principles of aneurysm formation and are unique in their dorsomedial location unrelated to an arterial bifurcation. Although their anatomy is straightforward and exposure is not restricted by bone or dural structures of the skull base, they possess extremely fragile necks which make surgical management particularly hazardous. 相似文献
87.
OA Ayangbile JP Fontenot PP Graham DJ Kirk VG Allen 《Canadian Metallurgical Quarterly》1998,76(3):686-693
Exacerbations of asthma have been associated with exposure to ozone or particles with a 50% cut-off aerodynamic diameter of 10 microm (PM10). We postulated in this study that the association of summertime air pollution (i.e. ozone and PM10) with acute respiratory symptoms, medication use and peak expiratory flow differs among patients grouped according to asthma severity. During the summer of 1995, effects of ambient air pollution on these parameters were studied in a panel of 60 nonsmoking patients with intermittent to severe persistent asthma. These patients were recruited from our Pulmonary Out-patient Clinic. Subgroup analysis was performed on the degree of hyperresponsiveness and lung steroid use before the start of the study, as indictors for the severity of asthma. Associations of the parameters studied with ozone, PM10, nitrogen dioxide (NO2), sulphur dioxide (SO2) and black smoke were evaluated using time series analysis. Several episodes with increased summertime air pollution occurred during the 96 day study period. Eight hour average ozone concentrations exceeded the World Health Organization (WHO) Air Quality Guidelines (120 microg x m(-3)) on 16 occasions. Daily mean levels of PM10 were moderately elevated (range 16-98 microg x m(-3)). Levels of the other measured pollutants were low. There was a consistent, positive association of the prevalence of shortness of breath (maximal relative risk (RRmax) 1.18) with ozone, PM10, black smoke and NO2. In addition, bronchodilator use was associated with both ozone and PM10 levels (RRmax 1.16). Stratification by airway hyperresponsiveness and steroid use did not affect the magnitude of the observed associations. No associations with peak expiratory flow measurements were found. We conclude that the severity of asthma is not an indicator for the sensitivity to air pollution. 相似文献
88.
Drug reactions in patients with HIV infection, e.g. fever or rash, are a frequently occurring clinical problem. These side effects particularly are observed with sulfonamides; however, many other drugs have also shown to induce allergic reactions when given to patients with HIV infection. The production of hydroxylamines has been put forward as one of the explanations for these high incidence of reactions on drugs. Since sulfonamides are the first choice of therapy for the treatment and prophylaxis of Pneumocystis carinii pneumonia, several strategies have been developed to circumvent drug reactions. In general rechallenge or desensitization are recommended in literature. This article discusses the results and risks of rechallenge and desensitization with sulfonamides or other drugs, as mentioned in the literature. Furthermore preliminary results of rechallenge with a sulfonamide, which is not metabolized into hydroxylamines, are presented. From the data in the literature it is concluded that desensitization should be preferred to rechallenge. 相似文献
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90.
PP Weinstein 《Canadian Metallurgical Quarterly》1998,84(4):730-738
In this prospective, multicenter, double-blind study, the efficacy of ciprofloxacin was compared with that of clarithromycin as therapy for patients with acute bacterial exacerbations of chronic bronchitis (ABECB) from whom a pretherapy pathogen was isolated; the efficacy was measured by the infection-free interval. Clinical and microbiological responses at the end of therapy were secondary efficacy variables. Patients randomly received either ciprofloxacin or clarithromycin (500 mg twice a day for 14 days). Three hundred seventy-six patients with acute exacerbations of chronic bronchitis were enrolled in the study of whom 234 had an ABECB. Clinical resolution was observed in 90% (89 of 99) of ciprofloxacin recipients and 82% (75 of 91) of clarithromycin recipients for whom efficacy could be evaluated. The median infection-free interval was 142 days for ciprofloxacin recipients and 51 days for clarithromycin recipients (P = .15). Bacteriologic eradication rates were 91% (86 of 95) for ciprofloxacin recipients and 77% (67 of 87) for clarithromycin recipients (P = .01). In summary, compared with clarithromycin, treatment of ABECB with ciprofloxacin was associated with a trend toward a longer infection-free interval and a statistically significantly higher bacteriologic eradication rate. 相似文献