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61.
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The mechanism of the relaxant action of isoquinolines on smooth muscle is conjectural. In order to gain further insight into the intestinal action of isoquinolines, we have synthesized an isoquinoline derivative which can be radioiodinated, resulting in the obtention of a ligand with a high specific activity. 6,7-Dimethoxy-4-(4'-aminobenzyl) isoquinoline (DMABI) is an arylamine analogue of the most relaxating isoquinoline derivative, i.e., 6,7-dimethoxy-4-(4'-chlorobenzyl) isoquinoline. Its iodinated derivative, 6,7-dimethoxy-4-(4'-amino-3'-[125I]iodobenzyl) isoquinoline (125I-DMABI) binds reversibly to rat intestinal membranes. Binding is rapid, saturable, and temperature dependent. The binding of 125I-DMABI to intestinal membranes is competitively inhibited by identical concentrations of unlabeled DMABI or iodo-DMABI in the range between 10(-8) and 10(-5)M. Scatchard analysis indicates the existence of two classes of binding sites: a class with a low capacity (14 +/- 2 pmol/mg of protein) and a Kd = 0.10 +/- 0.02 microM, and a class with a high capacity (240 +/- 31 pmol/mg of protein) and a Kd = 8.0 +/- 1.1 microM. Specific binding of the radioiodinated ligand is inhibited by a variety of 4-benzyl isoquinolines and 1-benzyl isoquinolines. Structure-activity relationship demonstrates the primordial role of C-6 and C-7 methoxy groups and the important role of 4-benzyl on configuration related to the isoquinoline nucleus. A high significant correlation between competitive binding (Ki) and relaxant effect in rat intestine (IC50) is observed and strongly suggests that the isoquinoline-binding site mediates the pharmacologic response. Upon photolysis, this ligand incorporates irreversibly into rat intestinal membranes. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography reveal a major 125I-DMABI-labeled protein with molecular weight of 36,000 and two minor proteins with molecular weights of 52,000 and 26,000. The labeling of these proteins is specific since it is completely abolished by 100 microM DMABI. Scanning of autoradiographs and integration of peaks show that the probe binds with the same apparent affinity to the three proteins. These findings indicate the utility of this novel high affinity radioiodinated probe as a tool for elucidating the mechanism of action of isoquinoline. 相似文献
63.
The direction of venous return was monitored continuously by the Doppler method at 4 MHz, in order to study the effects of posture and certain kinesitherapeutic maneuvers on venous return in the foot of young, healthy and trained adults (kinesitherapy monitors, yoga assistants). It was noted that: the acceleration of venous return in the foot was expiratory in the recumbent position and inspiratory in the standing position; dorsiflexion (leg on foot or toes on heel) caused a more pronounced spurt phenomenon than plantar flexion; massage repeated at high frequency is less beneficial for venous return than slower massage, which allows better adaptation of venous compliance. 相似文献
64.
Prof. Dr. Graziella Bernocchi Elda Scherini Silvia Giacometti Vladislav Mareš 《Anatomical record (Hoboken, N.J. : 2007)》1990,228(4):461-470
Replicative synthesis of DNA in the brain of the adult frog was studied by light microscope autoradiography. Animals collected during the active period (May–June) and in hibernation (January) were used. In active frogs, 3H-thymidine labelling occurred mainly in the ependymal cells which line the ventricles. The mean labelling index (LI%) was higher in the ependyma of the lateral and fourth ventricles than in the ependyma of the lateral diencephalon and tectal parts of the mesencephalon. In the recessus infundibularis and preopticus the number of labelled cells (LCs) was several times greater than in the lateral parts of the third ventricle. LCs were seen subependymally only occasionally. The incidence of LCs in the parenchyma of the brain was much lower in most regions than in the ventricular ependyma; LCs were mainly small and, from their nuclear morphology, they were glial cells. The LI% reached the highest value in the septum hippocampi and in the nucleus entopeduncularis. In these locations, LCs were larger and closer in size to the nerve cells of these regions. From comparison with data obtained earlier in the brain of mammals, it is evident that the distribution of proliferating cells in the olfactory and limbic system is phylogenetically conservative. The occurrence of pyknotic cells in the same areas which contain LCs, suggests that cell division reflects in part the process of cell renewal observed in mammals. However, proliferating cells could also be linked to the continuous growth observed in non-mammalian vertebrates. In hibernating frogs, LCs and pyknoses were not seen or were found occasionally, which further indicates the functional significance of both processes. 相似文献
65.
Bassetti M Righi E Fasce R Molinari MP Rosso R Di Biagio A Mussap M Pallavicini FB Viscoli C 《The Journal of antimicrobial chemotherapy》2007,60(2):433-435
OBJECTIVES: Ventilator-associated pneumonia (VAP) is a frequent complication of patients admitted to intensive care units (ICUs). Ertapenem is a newer carbapenem with good in vitro activity against extended-spectrum beta-lactamase (ESBL)-producing organisms. However, there are no clinical data to support the use of ertapenem in VAP. Our purpose is to evaluate the usefulness and safety of ertapenem in the treatment of VAP caused by susceptible ESBL strains. METHODS: Ertapenem 1 g daily intravenously was given to adult patients with signs and symptoms of VAP beginning within 7 days of mechanical ventilation and caused by ESBL-producing Gram-negative organisms. RESULTS: From June 2005 to June 2006, we enrolled 20 adult patients hospitalized in an ICU and diagnosed with VAP due to Gram-negative ESBL strains. Causative organisms identified as ESBL producers susceptible to ertapenem were Klebsiella pneumoniae (alone in 10 cases and with methicillin-resistant Staphylococcus aureus in 4 cases), Enterobacter cloacae (2), Proteus mirabilis (2) and Citrobacter freundii (2). Clinical success was achieved in 16/20 (80%) of the clinically evaluable patients and in 15/20 (75%) of the microbiologically evaluable patients. The drug was well-tolerated; one patient presented a transient increase in liver enzymes. CONCLUSIONS: We believe this is one of the first reports to demonstrate that ertapenem has clinical utility in treating serious infections caused by ESBL-producing organisms. Ertapenem appears to be suitable for ESBL VAP therapy. This pilot study suggests subsequent controlled randomized trials in this indication. 相似文献
66.
67.
Agnes Ricard-Hibon Jean-Louis Ducassé Philippe Ravaud Chantal Wood Eric Viel Marcel Chauvin Fabrice Brunet Gérard Bleichner 《European journal of emergency medicine》2004,11(4):198-203
OBJECTIVE: This national survey was carried out to evaluate the quality programme for acute pain management in the emergency department (ED) and in pre-hospital emergency medical services (EMS). METHODS: Two types of questionnaires were sent to the chief consultant and the chief nurse of all ED and EMS. Data collected were: the type of structure, quality programme organization, acute pain management, and the training needs to initiate a pain quality programme. RESULTS: A total of 363 questionnaires were recorded (198 from chief consultants) with 98% of questionnaires being usable. A pain management committee existed in 71% of cases, a quality committee in 83%. A complete quality control procedure existed in 53% of units. An audit on pain management was carried out in only 23% of cases. Training in quality was performed for 64% of physicians and 68% of nurses. Training specifically for pain management was carried out for physicians in 56% of cases and for nurses in 68% of cases. Pain therapeutics protocols existed in 69% of cases. Pain intensity was evaluated 'systematically or often' in 64% at the beginning of patient management, and in 56% at the end of patient management. The staff was 'not very motivated' for a pain management quality programme in less than 3% of responses. A total of 61% of chief consultants and 58% of chief nurses requested advice. CONCLUSION: Most ED and EMS units seem to master the quality control programme methodology. Units are highly motivated to initiate a quality control programme on pain. Nevertheless, its implementation could benefit from some external support. 相似文献
68.
Lestuzzi C Viel E Mimo R Meneguzzo N 《The international journal of cardiovascular imaging》2001,17(2):107-110
We describe a rare case of small-cell lung carcinoma invading the left atrium through a pulmonary vein. Echocardiography was particularly useful in this case in assessing the intracavitary extension of the tumor and the outcome of therapy. Echocardiography is a low-cost, easy imaging tool, complementary to radiological techniques and useful in evaluating thoracic tumors involving the cardiovascular structures. 相似文献
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