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71.
Ba2+ differentially inhibits the Rb+ efflux promoting and the vasorelaxant effects of levcromakalim and minoxidil sulfate in rat isolated aorta 总被引:1,自引:0,他引:1
Ulrich Quast Yves Baumlin Cornelia Löffler 《Naunyn-Schmiedeberg's archives of pharmacology》1995,353(1):86-93
The K+ channel openers activate ATP-sensitive K+ channels (KATP) in vascular smooth muscle and induce relaxation. In this study, the relationship between these two effects was examined in rings of rat aorta using levcromakalim and minoxidil sulfate as the openers and Ba2+ as the K+ channel blocker; K+ channel opening was assessed by determining the rate constant of 86Rb+ efflux from the preparation.Ba2+ inhibited the 86Rb+ efflux stimulated by levcromakalim in a noncompetitive manner with an IC50 value of 29 M and a Hill-coefficient of 1.2. At concentrations > 300 M, Ba2+ increased the tension of rat aortic rings concentration-dependently. Levcromakalim relaxed contractions to Ba2+ (0.5 and 1 mM) with potencies similar to those determined against KCl (25 mM) or noradrenaline as spasmogens (EC50 values 15–40 nM). The vasorelaxant effect against Ba2+ was inhibited by the KATP channel blockers, glibenclamide and tedisamil, and abolished in depolarizing medium (55 mM KCl). At 3 mM Ba2+, levcromakalim was still able to transiently induce complete relaxation; however, within 1 h oscillations in tension developed, leading to a stable level of only 15% relaxation. A similar level of relaxation was achieved against 10 mM Ba2+ whereas the combination of 0.5 mM Ba2+ and 3 M tedisamil blocked the relaxant effect of levcromakalim completely. With minoxidil sulfate as the KATP channel opener the results of the 86Rb+ efflux and tension experiments were similar to those obtained with levcromakalim.It is concluded that Ba2+ is more potent in inhibiting the K+ channel opening than the vasorelaxant effects of the openers. On the basis of the 86Rb+ efflux experiments it is estimated that at least 97% of the channels opened by the activators can be blocked without major effects on vasorelaxation suggesting a dissociation between the two effects. However, if the block is pushed to extremes ( 99.95%) the vasorelaxant effect of the openers is also abolished suggesting a link between both effects. This paradoxon remains to be solved. 相似文献
72.
Savi A Rossetti C Gilardi MC Landoni C Rizzo G Ippolito M Garraffa G Lucignani G 《La Radiologia medica》1999,98(1-2):36-42
PURPOSE: We investigated 201Tl myocardial uptake with(out) nonuniform attenuation compensation in ischemic myocardiopathy patients. The segmental patterns of the two types of SPECT images were compared with PET [13N]NH3 studies performed in the same patient. PET images were taken as reference and the diagnostic accuracy of SPECT with(out) attenuation correction was evaluated. MATERIAL AND METHODS: During the SPECT study transmission and emission data were simultaneously recorded by a triple head gamma camera equipped with fan beam collimators and a 99mTc transmission line source (740MBq). SPECT and PET images, the former reconstructed with(out) attenuation correction, were corecorded and reoriented along the short axis. The left ventricular wall was divided into 11 segments and segmental activity normalized to maximum in each study. RESULTS: Statistically significant differences were found between PET/(un)corrected SPECT ratios in posterior and septal segments. In these myocardial regions, attenuation correction compensates for attenuation artifacts, by correcting the underestimation of radioactivity concentration caused by radiation absorption. A statistically significant difference was also found in midventricular anterior and apical segments (p < .05). However, in these regions attenuation correction results in a decrease in corrected relative to uncorrected SPECT activity. The agreement rate with PET data is higher for corrected SPECT (mean differences were 3.12 +/- 11.51 and 2.19 +/- 8.63 for uncorrected versus corrected SPET). We had 50% positive and 77% negative predictive value without attenuation correction, versus up to 69% and 90%, respectively, with attenuation correction. CONCLUSIONS: The attenuation correction procedure with simultaneous transmission-emission effectively reduces attenuation artifacts in SPECT myocardial imaging. While diagnostic accuracy increases in posterior and septal myocardial regions, anterior and apical data need careful interpretation because a relative decrease in radioactivity concentration can be observed after attenuation correction. 相似文献
73.
Buolamwini John K. Raghavan Krishnamchari Fesen Mark R. Pommier Yves Kohn Kurt W. Weinstein John N. 《Pharmaceutical research》1996,13(12):1892-1895
Purpose. A QSAR study based on electrotopological state (E-state) indices was conducted for a series of flavone HIV-1 integrase inhibitors to guide drug design.
Methods. E-state indices formulated to encode electronic and topological information for each skeletal atom in a molecule (Kier and Hall Pharm. Res. 7:801–807 (1990)) were calculated using the Molconn-X program, and partial least squares (PLS) multivariate regression was used to derive QSAR models.
Results. Predictive models with correlation coefficients (r2) of 0.98 (3 PLS components) and 0.99 (5 PLS components) and corresponding cross-validated correlation coefficients (c.v. r2) of 0.51 and 0.73, were obtained for inhibition of cleavage and integration, respectively, with one molecule omitted from the analysis.
Conclusions. E-state indices at C6, C3, C5, C5, and O4 were found to be more important for prediction of activity than those for any of the other 12 flavone skeletal atoms that are common to the molecules in the data set. 相似文献
74.
M Rossetti 《Helvetica chirurgica acta》1978,45(1-2):71-73
The collective term "recurrent hiatus hernia" groups the pseudo-recurrent lesions after inappropriate surgery together with true recurrencies. An early recurrency can often be attributed to surgical technique, a late recurrency is usually biological in nature. The manifold pathophysiology of these cases is dominated by an intercurrent relux, dysphagia or paraoesophageal stomach volvulus. A decision to operate must, because of the important technical risks inherent, be made only after fully exhausting the conservative alternatives. The reoperation requires surgeon specially qualified for the task, with experience in thoraco-abdominal procedures. Approaches and alternative operating techniques are discussed with reference to personal experience from 56 cases. 相似文献
75.
Yves Bécouarn Binh Nguyen Bui René Brunet Alain Ravaud 《Cancer chemotherapy and pharmacology》1991,29(2):159-163
Summary A total of 2,238 new cancer patients were treated in our institution in 1988; among the 423 (18.9%) who were>70 years old, 51 underwent chemotherapy. The median age was 75.8 years, and the Karnofsky performance status (KPS) was 70% for 40 patients. Malignancies were hematopoietic in 24 cases (47%) and digestive in 15 patients (29%), and 12 subjects (24%) had other types of cancers. The first chemotherapy course was given at the full dose to 23/51 (45.1%) patients. The drug dose was reduced for 28/51 (54.9%) patients, due in 25 cases to the subjects being>70 years old. Neither age, KPS, pretreatment assessment, nor cancer extent was correlated with the modifications made to the first cycle. An overall toxicity of grade 3+4 (WHO grading scale) was noted in 10 subjects (19.6%). Although these elderly patients were probably selected, analysis of their charts did not evidence an increase in chemotherapy toxicity, regardless of the dose they received.Presented at the EORTC Pharmacokinetics and Metabolism Group Meeting, Bordeaux, November 1990 相似文献
76.
D. Cremaschi C. Rossetti M. T. Draghetti C. Manzoni V. Aliverti 《Pflügers Archiv : European journal of physiology》1991,419(5):425-432
Transepithelial pathways of macromolecule transport have been studied in vitro in rabbit nasal respiratory mucosa, maintained at 27° C. Transepithelial electrical potential difference, short-circuit current and resistance were 3.4±0.5mV (submucosa positive), 65.0±6.7 A cm–2 and 52.1±5.6 cm–2 respectively (n=15). These electrical characteristics are those of a leaky epithelium allowing macromolecules to permeate paracellularly. A detailed permeation study of a polypeptide (elcatonin, M
w=3362) was also undertaken. Elcatonin mucosa-submucosa (J
ms) and submucosa-mucosa (J
sm) fluxes were measured by radioimmunoassay. With 10 g/ml elcatonin, J
ms was significantly larger than J
sm for the whole 120-min period of observation; net flux showed a maximum in the first 30 min (J
ms=13.6±1.0 ng cm–2 h–1, J
sm=1.4±0.1 ng cm–2 h–1, n=10). J
ms fell towards the value of J
sm if the temperature was reduced to 4°C or if the mucosa was simultaneously treated with 0.1 mM dinitrophenol and 3 mM monoiodoacetate. J
ms and J
net followed saturation kinetics with increasing elcatonin concentrations. Adrenocorticotropic hormone (M
r=4500) produced a similar pattern to elcatonin. However, J
ms and J
sm were not significantly different from each other at any time either for [3H]sucrose (M
w=342) or for [14C]polyethyleneglycol-4000 (M
w=4000) when present in the bathing medium at 500 M concentration. The results show active transport of polypeptides in parallel with passive permeation (possibly through leaky intercellular junctions). Active transport does not appear to be related to nonspecific pinocytosis but to receptor-mediated endocytosis. The latter may be important for the sampling of potential antigens from the nasal lumen. 相似文献
77.
Yves Claustre Danielle De Peretti Philippe Brun Christiane Gueudet Nathalie Allouard Richard Alonso Jo?lle Lourdelet André Oblin Gabrielle Damoiseau Dominique Fran?on Marie-Fran?oise Suaud-Chagny Régis Steinberg Mireille Sevrin Hans Schoemaker Pascal George Philippe Soubrié Bernard Scatton 《Neuropsychopharmacology》2003,28(12):2064-2076
SSR181507 ((3-exo)-8-benzoyl-N-[[(2S)7-chloro-2,3-dihydro-1,4-benzodioxin-1-yl]methyl]-8-azabicyclo[3.2.1]octane-3-methanamine monohydrochloride) is a novel tropanemethanamine benzodioxane derivative that possesses high and selective affinities for D2-like and 5-HT(1A) receptors (K(I)=0.8, 0.2, and 0.2 nM for human D(2), D(3), and 5-HT(1A), respectively). In vivo, SSR181507 inhibited [(3)H]raclopride binding to D(2) receptors in the rat (ID(50)=0.9 and 1 mg/kg, i.p. in limbic system and striatum, respectively). It displayed D(2) antagonist and 5-HT(1A) agonist properties in the same concentration range in vitro (IC(50)=5.3 nM and EC(50)=2.3 nM, respectively, in the GTPgammaS model) and in the same dose range in vivo (ED(50)=1.6 and 0.7 mg/kg, i.p. on striatal DA and 5-HT synthesis, respectively, and 0.03-0.3 mg/kg, i.v. on dorsal raphe nucleus firing rate). It selectively enhanced Fos immunoreactivity in mesocorticolimbic areas as compared to the striatum. This regional selectivity was confirmed in electrophysiological studies where SSR181507, given acutely (0.1-3 mg/kg, i.p.) or chronically (3 mg/kg, i.p., o.d., 22 days), increased or decreased, respectively, the number of spontaneous active DA cells in the ventral tegmental area, but not in the substantia nigra. Moreover, SSR181507 increased both basal and phasic DA efflux (as assessed by microdialysis and electrochemistry) in the medial prefrontal cortex and nucleus accumbens, but not in the striatum. This study shows that the combination of D(2) receptor antagonism and 5-HT(1A) agonism, in the same dose range, confers on SSR181507 a unique neurochemical and electrophysiological profile and suggests the potential of this compound for the treatment of the main dimensions of schizophrenia. 相似文献
78.
Daniela S Pontes Fernanda A Dorella Luciana A Ribeiro Anderson Miyoshi Yves Le Loir Alexandra Gruss Sérgio C Oliveira Philippe Langella Vasco Azevedo 《Journal of drug targeting》2003,11(8-10):489-493
The Brucella abortus ribosomal protein L7/L12 is an immunodominant antigen and an interesting candidate for the development of oral live vaccines against brucellosis. Here, a recombinant Lactococcus lactis strain producing L7/L12 under the control of nisin inducible promoter was orally administered to BALB/c mice. Significant levels of anti-L7/L12 specific IgA detected in feces revealed an induced local humoral immune response. However, serum analysis did not reveal any anti-L7/L12 antibodies suggesting the absence of a systemic response. Nevertheless, the vaccinated mice showed a partial protective immunity against B. abortus virulent strain (S2308) challenged by intraperitoneal inoculation. 相似文献
79.
Marc-David Leclair Olivier Hartmann Yves Heloury Laurent Fourcade Anne Laprie Fran?oise Mechinaud Caroline Munzer Herve Rubie 《Journal of clinical oncology》2004,22(9):1689-1695
PURPOSE: To assess the results and morbidity of treatment of children with localized pelvic neuroblastoma (NB). PATIENTS AND METHODS: All consecutive cases of localized pelvic NB registered in the French multicenter prospective studies NBL90 and NBL94 between 1990 and 1999 were reviewed. Resectability was decided on the basis of clinical and radiologic evaluation. In unresectable tumors, primary chemotherapy (combinations of carboplatin-etoposide and vincristine-cyclophosphamide-doxorubicine) was administered before surgery. RESULTS: Forty-seven children (with 26 resectable tumors and 21 unresectable) were included in this study. At the end of treatment, 31 children were in complete remission (66%). Long-term neurologic sequelae were observed in seven patients (15%), directly attributable to surgery in three cases. After a median follow-up of 48 months (range, 13 to 129 months), 44 patients are alive. Six children experienced local relapse; four of these children achieved subsequent remission. The projected overall survival and event-free survival (EFS) rates at 5 years are, respectively, 93% +/- 4% and 84% +/- 5%. Survival of children treated with preoperative chemotherapy are similar to those treated by primary surgery (80% and 88% respectively). The extent of surgical resection seemed to have no influence on the outcome (EFS rates 76% and 89% in case of gross residue and complete resection or microscopic residue, respectively). CONCLUSION: Our data confirm the excellent survival of localized pelvic NBs. Considering the efficacy of preoperative chemotherapy, patients with pelvic NB should be carefully screened for primary surgery. The risk of neurologic impairment during radical excision should be balanced with the good survival of children with minimal residual disease. 相似文献
80.
Darius Razavi Isabelle Merckaert Serge Marchal Yves Libert Sandrine Conradt Jacques Boniver Anne-Marie Etienne Ovide Fontaine Pascal Janne Jean Klastersky Christine Reynaert Pierre Scalliet Jean-Louis Slachmuylder Nicole Delvaux 《Journal of clinical oncology》2003,21(16):3141-3149
PURPOSE: Although there is wide recognition of the usefulness of improving physicians' communication skills, no studies have yet assessed the efficacy of post-training consolidation workshops. This study aims to assess the efficacy of six 3-hour consolidation workshops conducted after a 2.5-day basic training program. METHODS: Physicians, after attending the basic training program, were randomly assigned to consolidation workshops or to a waiting list. Training efficacy was assessed through simulated and actual patient interviews that were audiotaped at baseline and after consolidation workshops for the consolidation-workshop group, and approximately 5 months after the end of basic training for the waiting-list group. Communication skills were assessed according to the Cancer Research Campaign Workshop Evaluation Manual. Patients' perceptions of communication skills improvement were assessed using a 14-item questionnaire. RESULTS: Sixty-three physicians completed the training program. Communication skills improved significantly more in the consolidation-workshop group compared with the waiting-list group. In simulated interviews, group-by-time repeated measures analysis of variance showed a significant increase in open and open directive questions (P =.014) and utterances alerting patients to reality (P =.049), as well as a significant decrease in premature reassurance (P =.042). In actual patient interviews, results revealed a significant increase in acknowledgements (P =.022) and empathic statements (P =.009), in educated guesses (P =.041), and in negotiations (P =.008). Patients interacting with physicians who benefited from consolidation workshops reported higher scores concerning their physicians' understanding of their disease (P =.004). CONCLUSION: Consolidation workshops further improve a communication skills training program's efficacy and facilitate the transfer of acquired skills to clinical practice. 相似文献