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排序方式: 共有1385条查询结果,搜索用时 15 毫秒
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Dr. Blijke S. Kroezen Gabriele Conti Benedetta Girardi Dr. Jonathan Cramer Dr. Xiaohua Jiang Dr. Said Rabbani Jennifer Müller Maja Kokot Enrico Luisoni Prof. Daniel Ricklin Dr. Oliver Schwardt Prof. Beat Ernst 《ChemMedChem》2020,15(18):1706-1719
Siglecs are members of the immunoglobulin gene family containing sialic acid binding N-terminal domains. Among them, Siglec-8 is expressed on various cell types of the immune system such as eosinophils, mast cells and weakly on basophils. Cross-linking of Siglec-8 with monoclonal antibodies triggers apoptosis in eosinophils and inhibits degranulation of mast cells, making Siglec-8 a promising target for the treatment of eosinophil- and mast cell-associated diseases such as asthma. The tetrasaccharide 6’-sulfo-sialyl Lewisx has been identified as a specific Siglec-8 ligand in glycan array screening. Here, we describe an extended study enlightening the pharmacophores of 6’-sulfo-sialyl Lewisx and the successful development of a high-affinity mimetic. Retaining the neuraminic acid core, the introduction of a carbocyclic mimetic of the Gal moiety and a sulfonamide substituent in the 9-position gave a 20-fold improved binding affinity. Finally, the residence time, which usually is the Achilles tendon of carbohydrate/lectin interactions, could be improved. 相似文献
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M Souquet T Restle R Krebs SF Le Grice RS Goody BM W?hrl 《Canadian Metallurgical Quarterly》1998,37(35):12144-12152
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The systemic, coronary and regional vascular responses to the K+ATP channel opener lemakalim were compared to other potent vasodilators (i.e., nifedipine, adenosine, nitroglycerin and acetylcholine). Experiments were performed in 12 conscious dogs 2 to 4 weeks after implantation of aortic catheters and flow probes on the ascending aorta, left circumflex coronary, celiac, mesenteric, renal and iliac arteries, and solid-state miniature pressure gauges in the left ventricular cavity. Dose-response curves induced by bolus injection (i.v.) were examined. For doses that reduced total peripheral resistance by 22%, lemakalim reduced celiac (-28 +/- 2%), mesenteric (-24 +/- 3%), renal (-17 +/- 3%) and iliac (-18 +/- 3%) vascular resistances (i.e., by amounts similar to those observed with the other vasodilators, except for adenosine, which increased renal resistance). At these doses, lemakalim induced a greater decrease (-52 +/- 3%) (P < .05) in coronary resistance, as compared with nifedipine (-35 +/- 3%), adenosine (-38 +/- 3%), nitroglycerin (-25 +/- 2%) and acetylcholine (-32 +/- 3%). However, when near maximal vasodilation was elicited, adenosine elicited the greatest (P < .05) decrease in coronary resistance (-81 +/- 1%), as compared with lemakalim (-74 +/- 2%), nifedipine (-67 +/- 2%), nitroglycerin (-63 +/- 2%) and acetylcholine (-72 +/- 1%). Both the time to maximal increases in regional blood flow and the time for recovery in all vascular beds were significantly prolonged for lemakalim compared with the other vasodilators. Thus, the K+ATP channel opener lemakalim dilates the coronary bed out of proportion to other vascular beds, is relatively more potent at lower doses than other vasodilators and exhibits a delayed and more prolonged action in all regional vascular beds. 相似文献
5.
L Giorgi A Di Filippo A Franchini L Rizzo S Benvenuti M Conti GP Novelli 《Canadian Metallurgical Quarterly》1994,60(1-2):43-47
OBJECTIVE: The reflex response to orotracheal intubation provokes an increase of arterial pressure accompanied by an increase of chorioides volume and a consequent ocular hypertone. There are several methods to reduce the reflex response due to intubation. One of the most effective is topical anaesthesia of larynx and trachea. Experiments were directed to evaluate the efficacy of topical anaesthesia to reduce the intraocular hypertone due to orotracheal intubation. DESIGN: A prospective randomized mask study was conduct on patients undergoing ophthalmologic (anterior segment) surgery at the Eye Clinic of Florence University. METHODS: Intraocular pressure was measured by a Goldman tonometer at four times: T0 = basal, T1 = 2' minutes after induction of general anaesthesia, T2 = 2' minutes after laryngoscopy, T3 = 2' minutes after orotracheal intubation. At the same moments, systolic blood pressure, heart rate, rate pressure pro duct were measured. Patients were randomly divided in two groups: Group L (n = 10) in which was evaluated the efficacy of laryngotracheal topical spray of lidocaine 4% (2 ml) and Group F (n = 10) in which saline was used instead of anesthetic. The filling of the LTA kit (Abbott) was made by a person not involved in the experiments. DATA ANALYSIS: Student's t test for unpaired data. RESULTS: Topical anaesthesia reduces the increase of intraocular pressure, hypertension and rate pressure product due to intubation. The intraocular pressure reduces to 13% less than basal value in Group L and increase to 50% more than basal value in Group F. CONCLUSION: The topical anaesthesia of larynx and trachea is effective to reduce the intraocular hypertension due to the reflex response evoked by orotracheal intubation. 相似文献
6.
SF Breniere MF Bosseno C Barnabe S Urdaneta-Morales M Tibayrenc 《Canadian Metallurgical Quarterly》1993,88(1):163-165
Detection of a nondistended pyriform sinus on cross-sectional imaging studies represents a diagnostic dilemma. The finding may be an inconstant physiologic phenomenon without clinical significance, or it may be due to tissue thickening and lack of pliability related to neoplasia or inflammation. Rescanning during respiratory maneuvers may clarify the anatomy, but full patient cooperation is needed. We demonstrate a method (turning the patient's head away from the side of the nondistended sinus) that induces distention of the pyriform sinus but does not require active patient participation. 相似文献
7.
SF Zakharov SH Kwok H Sokoloff HT Chang SP Radko A Chrambach 《Canadian Metallurgical Quarterly》1998,19(10):1625-1630
An automated gel electrophoresis apparatus, recently available commercially, allows one to follow the band during electrophoresis in real time, and lends itself therefore to an evaluation of bandwidth as a function of migration time (the dispersion coefficient), resolution and band shape. These determinations assume the constancy of band area with migration time and at various gel concentrations. The purpose of the present study was to verify these assumptions. Representative proteins and sodium dodecyl sulfate (SDS)-proteins, either natively fluorescent or fluorescein carboxylate labeled, were found to exhibit band areas which approach constancy as a function of migration time in both agarose and polyacrylamide gel electrophoresis, provided that (i) the protein concentration under the band was low enough to obviate self-quenching of fluorescence; (ii) the separation of the protein of interest from contaminants had progressed sufficiently during the time at which band areas were measured; (iii) the baseline under the peak was sufficiently well defined. However, band areas decrease with increasing gel concentration. Protein peaks exhibited leading and trailing tails. The ratio of the combined tail area to total area appeared to be near-constant at varying migration times. However, that ratio increases with increasing gel concentration. The tail area does not appear to be an artifact of fluorometric detection since it is reproduced upon fluorimetric analysis of the protein eluted from gel slices after electrophoresis. However, it may be due to photochemical destruction under the conditions of repetitive fluorometric peak detection. 相似文献
8.
A coal-oil mixture (COM) was prepared from a South African coal and a synthetic oil derived from the same coal by hydroliquefaction. The settling and rheological properties of this mixture were compared with those of a mixture of the same coal with fuel oil. The synthetic oil mixture showed greater settling stability, comparable with that of a commercial COM containing additives. The increased stability may be related to polar compounds present in the oil and on the coal surface. 相似文献
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Serotonin [5-hydroxytryptamine(5-HT)] in the paraventricular nucleus (PVN) of rats has a suppressive effect on feeding behavior and causes a selective decrease in carbohydrate ingestion, specifically at the onset of the natural (dark) feeding period. Studies conducted here provide further evidence for this phenomena, showing a similar dose-related decrease in carbohydrate ingestion at dark onset after PVN injection of 5-HT or of the agonists, d-norfenfluramine or fluoxetine, which act through endogenous 5-HT. To further characterize the effects of this indoleamine on the macrostructure of feeding, a computer-automated data acquisition system was used to analyze macronutrient feeding patterns in freely feeding animals maintained on the pure diets of protein, carbohydrate, and fat. Results indicate that PVN administration of 5-HT at dark onset decreases intake of the carbohydrate nutrient by decreasing meal size, feeding time, and feeding rate for this nutrient and increasing the satiating effect of carbohydrate. These effects, which occur specifically during the first meal after injection, are opposite those seen after peripheral administration of the 5-HT receptor antagonist, metergoline. This drug stimulates feeding through a selective increase in carbohydrate intake, characterized by an increase in meal size, percent composition, and feeding time for this nutrient and a decrease in the satiety ratio for carbohydrate. These results implicate the serotonergic system in the termination of carbohydrate-rich meals that are prevalent during the early hours of the natural feeding cycle. 相似文献