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991.
Gbahou F Rouleau A Morisset S Parmentier R Crochet S Lin JS Ligneau X Tardivel-Lacombe J Stark H Schunack W Ganellin CR Schwartz JC Arrang JM 《Proceedings of the National Academy of Sciences of the United States of America》2003,100(19):11086-11091
G protein-coupled receptors (GPCRs) are allosteric proteins that adopt inactive (R) and active (R*) conformations in equilibrium. R* is promoted by agonists or occurs spontaneously, leading to constitutive activity of the receptor. Conversely, inverse agonists promote R and decrease constitutive activity. The existence of another pharmacological entity, referred to as "protean" agonists (after Proteus, the Greek god who could change shape), was assumed on theoretical grounds. It was predicted from the existence of constitutive activity that a same ligand of this class could act either as an agonist or an inverse agonist at the same GPCR. Here, we show that proxyfan, a high-affinity histamine H3-receptor ligand, acts as a protean agonist at recombinant H3 receptors expressed in the same Chinese hamster ovary cells. In support of the physiological relevance of the process, we show that proxyfan also behaves as a protean agonist at native H3 receptors known to display constitutive activity. On neurochemical and behavioral responses in rodents and cats, proxyfan displays a spectrum of activity ranging from full agonism to full inverse agonism. Thus, protean agonism demonstrates the existence of ligand-directed active states LR* different from, and competing with, constitutively active states R* of GPCRs, and defines a pharmacological entity with important therapeutic implications. 相似文献
992.
Video-assisted ALIF with cage and anterior plate fixation for L5-S1 spondylolisthesis 总被引:2,自引:0,他引:2
Aunoble S Hoste D Donkersloot P Liquois F Basso Y Le Huec JC 《Journal of spinal disorders & techniques》2006,19(7):471-476
INTRODUCTION: Spondylolysis and spondylolisthesis grade 0, 1, and 2 are mainly asymptomatic but with aging process and different factors some back pain can occur and lead to chronic low back pain. The conservative treatment with physiotherapy and steroid injection is the gold standard but in some cases is not efficient enough and a surgical treatment is proposed. OBJECTIVES: The goal of this study is to propose a new technique to treat grade 0, 1, and 2 spondylolisthesis with an anterior video-assisted fusion and stabilization. METHODS: Twenty patients with chronic low back pain since more than 2 years and resistant to conservative therapy were included in this protocol. Clinical signs and radicular pain were noted. They were evaluated preoperatively and postoperatively until the last follow up using Oswestry score and visual analog score (VAS) for leg and back pain. X-rays showed grade 0 (8 cases), 1 (10 cases), and 2 (2 cases) spondylolisthesis according to Meyerding classification with disc collapse (bulging disc). MRI showed in all cases a disc degeneration with at least black disc and/or endplates changes with Modic I or II. All patients were operated using an anterior video-assisted retroperitoneal approach, with discectomy and fusion using an anterior impacted cage filled with autologous cancellous bone from the iliac crest and an anterior fixation with a triangular plate (Pyramid, Medtronic, Memphis). The follow up at 3, 6, 12, and 24 months was done with clinical and radiologic evaluation. In case of problem a computed tomography scan was performed. RESULTS: There were 11 women and 9 men, with and average age of 39 years old and a BMI of 25.6. All spondylolistheses occurred at level L5. The average slippage was 19%. All L5S1 discs were black, 8 had a Modic I changes in the endplates and 2 had Modic II. The shape of L5 vertebra was abnormal (trapezoidal) in 7 cases. All anterior approaches were performed without vascular, urologic, or digestive complication. Blood loss was inferior to 100 mL. All patients had a soft brace for 8 weeks postoperatively. There was no retrograde ejaculation for the 9 men and no sexual dysfunction reported by the women. One patient had no pain relief and was reoperated for posterior pedicular screw fixation. It was obvious that there was a pseudarthrosis even after the posterior fixation and an anterior transperitoneal revision was performed with the removal of the interbody device and iliac crest bone graft packing alone. A propioni bacterium acnes germ was found responsible for the anterior nonunion. This revision surgery with antibiotics treatment was successful. One of the patients with grade 2 had an additional posterior screw fixation with a minimally invasive pedicle screw system (Sextant, Medtronic, Memphis). Nineteen patients had a good fusion at 2 years follow-up (95%), mean Oswestry score improved from 74% preoperative to 21% postoperative at the last follow-up. Visual analog score (VAS) for back pain improved from 6.5 to 2.7 and VAS for leg pain improved from 6.2 to 3.4. Satisfaction rate was 90%. All active patients except two, were back to work at an average of 5.5 months (6 wk to 1 y). The 2 patients still not working were the nonunion and a work compensation. CONCLUSIONS: The results of this technique compare favorably with posterior stabilization and fusion (posterior lumbar interbody fusion and postero-lateral fusion) reported in the literature. Unlike posterior lumbar interbody fusion, however, it seems that the complication rate due to the approach is much lower, the fusion rate is similar. Grade 2 SPL is the limitation of the technique. The main advantage of the technique is to avoid posterior muscle damage and a quick recovery with no blood loss. Preservation of adjacent level disease can be assessed only after long-term follow-up. 相似文献
993.
The dopamine D3 receptor mediates locomotor hyperactivity induced by NMDA receptor blockade 总被引:4,自引:0,他引:4
N-methyl-D-aspartate (NMDA)/glutamate receptor antagonists, like phencyclidine, generate schizophrenic-like symptoms in humans and behavioural abnormalities in animals, such as hyperactivity. We investigated the role of the dopamine D(3) receptor in locomotor hyperactivity produced in mice by dizocilpine (MK-801), another NMDA receptor antagonist, at a low dose (0.12 mg/kg). BP 897, a highly D(3) receptor-selective partial agonist, or nafadotride, a preferential D(3) receptor antagonist, both at low doses (1 mg/kg and lower), had no effects on spontaneous activity and completely inhibited MK-801-induced hyperactivity. Clozapine, an atypical antipsychotic, produced the same effect as BP 897 and nafadotride. Haloperidol, a typical antipsychotic, reduced both spontaneous activity and MK-801-induced hyperactivity. In D(3) receptor knockout mice, MK-801-induced hyperactivity was weaker than that observed in wild-type mice while BP 897 and nafadotride were inactive. On the contrary, the effects of clozapine and haloperidol, which target multiple receptors in addition to the D(3) receptor, were almost completely preserved in D(3) receptor knockout mice. Our results show that hyperactivity produced by a low dose of MK-801 is dependent upon D(3) receptor stimulation and constitutes the first simple response to assess the in vivo activity of D(3) receptor-selective drugs. In addition, since D(3) receptor antagonists and antipsychotics produced very similar effects, our results add to the growing evidence suggesting that D(3) receptor blockade might produce antipsychotic effects. 相似文献
994.
995.
There is increasing evidence that oxidized low-density lipoproteins (Ox-LDL) might be involved in the pathogenesis of atherosclerosis and it has been reported that polyphenols inhibit LDL peroxidation and atherosclerosis. Minimally oxidized LDL (mOx-LDL) induce cytotoxicity in cultured bovine aortic endothelial cells (BAEC). The goal of this study was to test the protective effect of five natural polyphenols isolated from the aerial parts of Marrubium vulgare L. against mOx-LDL-induced cytotoxicity in BAEC. Four phenylpropanoid glycosides (acteoside 1, forsythoside B 2, arenarioside 3, ballotetroside 4) and one non-glycosidic derivative (caffeoyl-l-malic acid 5) were tested. These compounds inhibited both copper (Cu 2+)- and 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH)-induced in vitro LDL oxidation and preserved the morphological aspects of BAEC during their incubation with mOx-LDL. Furthermore, they reduced the accumulation of aldehydes in the cultured medium during the incubation of BAEC with mOx-LDL and prevented cellular LDH leakage during this period. These data suggest that natural phenylpropanoids inhibit mOx-LDL-induced cellular toxicity and that inhibition of lipid peroxidation could be a key mechanism in the cytoprotective effect of these molecules. 相似文献
996.
Michel Sauvain Jean-Pierre Dedet Nicole Kunesch Jacques Poisson Jean-Charles Gantier Philippe Gayral Gerhard Kunesch 《Phytotherapy research : PTR》1993,7(2):167-171
The activities of various compounds isolated from plants traditionally used against leishmaniasis in populations from the tablelands of the Guyanas have been examined. The leishmanicidal activity of plant extracts was evaluated by in vitro testing on promastigote and amastigote stages of Leishmania amazonensis and by in vivo tests on L. amazonensis in mice. The leaves of Jacaranda copaia (Aublet) D. Don yielded two compounds: ursolic acid and jaracanone. Ursolic acid showed an interesting activity in vitro with an ED50 against amastigotes of 0.02 mM and no toxicity to macrophages at twice this dose. Jacaranone displayed a marked activity against promastigotes in vitro with an ED50 of 0.02 mM. Both compounds have weak in vivo antileishmanial activity. Similar synthetic compounds such as quinol and quinone acetates were prepared and showed increased activity in experimental cutaneous leishmaniasis in mice. 相似文献
997.
998.
Purification of membrane-bound aminopeptidase from rat brain: Identification of aminopeptidase M 总被引:1,自引:0,他引:1
Two different membrane-bound aminopeptidases were isolated from rat brain membranes, one with a puromycin sensitive activity and the other, not affected by 10 microM puromycin. The physicochemical, catalytic and immunological properties of the latter were compared to those of aminopeptidase M purified from rat kidney membranes and allowed us to conclude to large similarities between these two enzymes. Because the two brain aminopeptidases were both sensitive to bestatin, it remains to be established whether both or only aminopeptidase M is involved in endogenous enkephalin inactivation. 相似文献
999.
Jean-Charles Duclos-Vallée MD Antoine Hadengue MD Nathalie Ganne-Carrié MD Edith Robin MD Claude Degott MD Serge Erlinger MD 《Digestive diseases and sciences》1995,40(5):1069-1073
Summary We report a case of primary biliary cirrhosis-autoimmune hepatitis overlap syndrome treated with cyclosporine A. Features of primary biliary cirrhosis were pruritus, high titer of antimitochondrial antibodies, inflammatory infiltrates surrounding interlobular bile ducts, and periportal granuloma. Features suggestive of autoimmune hepatitis were high titer of antinuclear antibodies, very high total immunoglobulins, and piecemeal necrosis. Because corticosteroids and ursodeoxycholic acid were inefficient, cyclosporine A was started at a dose of 3 mg/kg/day. A dramatic improvement in clinical condition, liver tests, and histology was noted. Discontinuation of cyclosporine A was followed by a clinical and histological relapse. Cyclosporine A reintroduction was again associated with a significant improvement. This case report suggests that in corticoresistant cases cyclosporine A could be an effective therapy for primary biliary cirrhosis-autoimmune hepatitis overlap syndrome. 相似文献
1000.
Katarzyna Kie-Kononowicz Xavier Ligneau Jean-Charles Schwartz Walter Schunack 《Archiv der Pharmazie》1995,328(5):469-472
In search of structure-activity relationships among histamine H3-receptor antagonists, the imidazole ring of known H3-receptor antagonists was replaced by different heteroaromatic ring systems. Thus, pyrazoles with ether ( 4,5 ) and carbamate ( 6,7 ) moieties as functional groups were synthesized. Reaction of the hydrochloride of 4-(3-hydroxypropyl)pyrazole ( 1 ) with phenyl or benzyl isocyanates mainly gave the carbamates 6 and 7 , whereas a similar reaction with 1 as the free base furnished the N-carbamoylpyrazoles 8 and 9 . The bifunctional pyrazoles 10 and 11 were formed as by-products. The compounds obtained did not show significant H3-receptor antagonist activity in vitro (rat brain cortex) or in vivo (mouse brain). These results demonstrate the importance of the imidazole moiety for H3-receptor antagonists. The new compounds were also screened for H1-receptor antagonist activity on the isolated guinea-pig ileum and for H2-receptor antagonist activity on the isolated spontaneously beating guinea-pig right atrium. The substances showed only weak antagonistic activity at both histamine receptors H1 and H2. 相似文献