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21.
Alexander Mülsch Markus Hecker Petr I. Mordvintcev Anatoly F. Vanin Rudi Busse 《Naunyn-Schmiedeberg's archives of pharmacology》1993,347(1):92-100
Summary The molecular mechanism(s) underlying the vasodilator activity of CAS 936 (3-(cis-2,6-dimethylpiperidino)-N-(4-methoxybenzoyl)-sydnonimine) and its metabolites 3-(cis-2,6-dimethylpiperidino)-sydnonimine (C87 3754) and N-(cis-2,6-dimethylpiperidino)-N-nitroso-2-aminoacetonitril (C873786) was investigated. These compounds were tested for their relaxant activity in isolated rabbit arterial segments, activation of purified soluble guanylyl cyclase and release of nitric oxide (NO) in vitro and in vivo. C873754 and C873786 inhibited the noradrenalin-induced contraction and increased the cyclic GMP content of endothelium-denuded rabbit aortic and femoral segments, whereas CAS 936 was without effect. Similarly, both metabolites, but not CAS 936, activated purified soluble guanylyl cyclase (EC50 about 30 M) and released NO in buffered aqueous solutions, as detected by electron spin resonance (esr) spectrometry. Both in vitro and in vivo an accumulation of NO was detected by esr spectrometry in vascular tissues exposed to the metabolites of CAS 936, whereas a significant release of NO from CAS 936 was only detected in the isolated rabbit liver, but not in vascular tissue. It is conceivable, therefore, that the metabolites of CAS 936 appearing in the systemic circulation after hepatic biotransformation induce vasodilatation by release of NO and activation of soluble guanylyl cyclase in vascular smooth muscle. Moreover, the activation of soluble guanylyl cyclase in vitro by the metabolites of CAS 936 was significantly enhanced by co-incubation with certain particulate fractions from bovine aortic endothelial and smooth muscle cells. Thus, an enzymic release of NO from these metabolites in addition to their spontaneous decomposition may play a significant role for their vasodilator activity in vivo.Correspondence to A. Mülsch at the above address 相似文献
22.
The role of the common cold in asthma 总被引:1,自引:0,他引:1
Busse WW 《Journal of clinical pharmacology》1999,39(3):241-245
It has long been known that patients with viral respiratory infections develop temporary asthma-like symptoms or see a worsening of their existing asthmatic symptoms or develop full-blown asthma during the infection. It should not be surprising, in view of this observation, that these same viruses have been found to initiate the same inflammatory processes as seen and characterized in the asthmatic patient. This has clear implications for therapy of asthmatic patients. 相似文献
23.
The Medicinal Chemistry Section of IUPAC sent a questionnaire regarding academic training for medicinal chemists to major research pharmaceutical companies in various countries in July 1992 and again in July 1993. A total of 102 replies were received from 65 companies, mainly from Germany, Italy, Japan, the UK and the USA, and these have been analysed and the results are presented. Most companies (> 90%) indicated that they seek to hire organic chemists who may have received some additional education in medicinal chemistry, rather than hire specialists in medicinal chemistry. The subjects most often mentioned as being desirable for the additional education were biochemistry (or drug metabolism and pharmacokinetics), pharmacology and physiology, computer modelling and QSAR, and molecular biology. 相似文献
24.
H J Busse R Nilius 《Deutsche Zeitschrift für Verdauungs- und Stoffwechselkrankheiten》1983,43(6):241-245
A thickening of the stomach or intestinal wall as a result of neoplastic or inflammatory infiltrations can be principally recognized by sonography as a "Cocarde phenomen". The question of the accuracy of ultrasonic tomography in the recognition of infiltrative diseases of the gastrointestinal tract has been examined in a prospective study. 80 patients who were suspected of having such a disease were sonographed, using the real-time method. The diagnose were verified by an adequate comparative method, by surgery or autopsy. An infiltrative gastrointestinal disease was correctly diagnosed by sonography in 42 cases, including nine cases of gastric carcinoma and of 27 colon carcinoma. Two patients were suffering of Crohn's disease, and in the remaining four cases the final diagnoses were bulbitis, Ménétrier's disease, diverticulitis and penetrating ulcus ventriculi, respectively. In 27 cases an infiltrative gastro-intestinal disease was correctly exclused by sonography. Ultrasonic examination wrongly produced a negative diagnosis in five cases and a positive in six. Thus, the efficiency of the examination was 0,86, the sensitivity 0,89 and the specifity 0,82. Ultrasonic tomography should therefore be assigned a major place in gastrointestinal diagnostics, too. It could point the way in many cases. It is not possible, however, to exclude a disease by means of sonography. 相似文献
25.
T L Busse M L Khristova V I Simonov A A Kushch V M Stakhanova I G Kharitonenkov 《Voprosy virusologii》1991,36(5):361-364
A competitive time-resolved fluoroimmunoassay (TR-FIA) system for the detection of antibodies to protein p24 of HIV was developed on the basis of monoclonal antibodies. The advantages of this test system over analogous enzyme immunoassay system and commercial test system "Antigen" (USSR) were demonstrated. The newly developed test system of TR-FIA was used for examination of sera from HIV-infected persons. 相似文献
26.
Paul M. Busse M.D. Ph.D. Blake Cady M.D. Albert Bothe Jr. M.D. Roger Jenkins M.D. William V. McDermott M.D. Glenn Steele Jr. M.D. Ph.D. Michael D. Stone M.D. 《World journal of surgery》1991,15(3):352-356
The recognition of a high incidence of local failure following surgical management of adenocarcinoma of the gallbladder has led to the use of adjuvant radiation therapy. In order to deliver higher doses to the gallbladder bed, intraoperative radiation therapy (IORT) has been used both with and without external beam radiation.The experience to date is reviewed. Ten patients have been treated, all of whom had either gross residual or unresected disease. The median survival for the group was approximately 1 year. There were no long-term survivors. The IORT did not contribute to the overall morbidity.Because of the limited number of patients and the advanced nature of the disease, the role of IORT in the management of gallbladder carcinoma has yet to be determined. The utility of this modality will most likely reside in the treatment of minimal residual disease at the time of cholecystectomy rather than in the palliative treatment of unresectable tumors.
Resumen El reconocimiento de la elevada tasa de falla local en el tratamiento del adenocarcinoma de la vesícula biliar, ha motivado el uso de radioterapia adyuvante. Con el objeto de administrar altas dosis de irradiación al lecho de la vesícula billiar, se ha utilizado la radioterapia intraoperatoria (RTIO) con y sin irradiación externa.Se revisa la experiencia hasta la fecha. Diez pacientes han sido tratados, todos con enfermedad macroscópica residual o no resecable. La sobrevida media para el grupo fue de aproximadamente un año; no hay sobrevivientes a largo plazo. La RTIO no contribuyó a la morbilidad global.Debido al limitado número de pacientes y a lo avanzado de la enfermedad, el rol de la RTIO está aun por determinar. La utilidad de esta modalidad muy posiblemente habrá de residir en el tratamiento de enfermedad residual miima en el momento de la colecistectomiá, más qu en el tratamiento paliativo de tumores no resecables.
Résumé Reconnaître la fréquence importante des échecs locaux à la suite du traitement chirurgical de l'adénocarcinome de la vésicule a amené à ajouter la radiothérapie. Pour pouvoir donner des doses plus importantes au lit de la vésicule, l'irradiation peropératoire (IP) a été administrée à la fois avec et sans irradiation externe. L'expérience à ce jour a été passée en revue. Dix patients ont été traités qui avaient soit une grosse tumeur résiduelle soit un cancer non réséqué. La survie moyenne du groupe était d'un an à peu près. Il n'y a eu aucun survivant à long terme. L'IP n'a rien changé à la mortalité globale. Compte tenu du nombre limité des patients et de la nature avancée de la maladie, le rôle de l'IP dans le traitement du cancer de la vésicule reste à déterminer. La valeur de l'IP sera probablement de traiter la petite tumeur résiduelle au moment de la cholécystectomie plutôt que les tumeurs non résécables.相似文献
27.
Marrow regeneration after mechanical depletion 总被引:1,自引:0,他引:1
The origin of marrow regeneration after mechanical depletion was reinvestigated in mouse chimeras. The results were compatible with the local origin of stem cells from remnants of incompletely removed marrow, but not with their origin from a common precursor of both bone and hemopoietic cell lines. In transplanted femurs depleted by a modified technique of in vivo evacuation of marrow, hemopoietic regeneration failed to occur. The presence of hemopoietic stem cells in the Haversian canals was thus excluded. The demonstration of ample hemopoiesis with minimal bone formation in nondepleted controls in which bone marrow initially became necrotic provided new evidence that osteogenesis was not a prerequisite of hemopoietic regeneration. 相似文献
28.
The Stroke Unit concept of the German Neurological Society differs from its precedents in Scandinavia or the United Kingdom. Hallmarks of the German concept are very early onset of diagnosis and treatment, continuous surveillance of vital functions by bedside monitors and specialized care by a multiprofessional team. This comparison of two Stroke Units in Minden and Munich-Harlaching, working according to the new German concept, shows broad similarities in admission intervals, diagnostic procedures, treatment modalities and short term prognosis, with an exceedingly low in-hospital mortality of 3.4-5.6% and a high proportion of patients (64-69%) leaving the hospital with Barthel scores above 70. Ongoing studies will show how this kind of Stroke Unit treatment compares to general wards. 相似文献
29.
In the March issue of Annals of Oncology, Fossati et al. [1]presented what they called indirect evidence for the existenceof a wish bias in oncology trials that may lead to overestimationof treatment results when a drug is being considered an innovation.The authors observed a 相似文献
30.