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Zvi Laron Jenny Frenkel lrit Gil-Ad Beatrice Klinger Ernesto Lubin Patrick Wuthrich François Boutignon Vincent Lengerts Romano Deghenghi 《Clinical endocrinology》1994,41(4):539-541
OBJECTIVE Hexarelin is a new synthetic growth hormone releasing peptide. We have tested the efficacy of intranasal (i.n.) administration of hexarelin to stimulate plasma GH and have compared this to the intravenous (i.v.) administration of the peptide. PATIENTS Ten children with familial short stature (FSS) aged 5·5-15·5 years and two known GH deficient patients aged 24 and 28 years without GH treatment. METHODS All 12 subjects were submitted to i.v. (1 μg/kg) and i.n. (20 μg/kg) hexarelin tests with a one-week interval between tests. Blood samples for GH, TSH, fT4 and T3 were obtained at 0, 15, 30, 60, 90 and 120 minutes. The hormone determinations were made by standard radio-immunoassays (RIA). RESULTS Both the i.n. and i.v. administration of hexarelin induced a large GH response, the mean (±SD) being 72·2± 35·5 mU/l for the i.n. test and 79·6 ± 53·0 mU/l for the i.v. test. The peak GH in the i.v. test occurred at 15–30 minutes and in the i.n. test between 30 and 60 minutes. The GH deficient patients showed no GH response In either test. Plasma TSH decreased in the FSS children from a mean (±SD) of 1.0 ± 0·26 to 0·64±0 2 mU/l (P<0 005) during the i.n. test and from 1·0±0·3 to 0·7±0·3mU/l (P> 0 05) during the I.v. test. In the isolated GH deficient patient, plasma TSH decreased from 1·06±0·38 mU/l to 0·86±0·17 during the i.v. test and from 1·60±0·01 to 1·11±0·06mU/l during the i.n. test. There were no significant changes in plasma fT4 or T3 in any of the tests. CONCLUSIONS The synthetic hexapeptide hexarelin is a potent pituitary GH stimulator when administered intra-nasally. The GH response was similar to that observed after intravenous hexarelin. Simultaneously, there was a significant decrease in plasma TSH but the concentrations remained in the normal range. These findings appear to be of theoretical and practical relevance to the investigation and management of short children. 相似文献
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Nino Stocchetti 《Acta neurochirurgica》2006,148(4):492-492
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Edmo Atique Gabriel Rafael Fagionato Locali Carla Cristina Romano Alberto José da Silva Duarte José Honório Palma Enio Buffolo 《European journal of cardio-thoracic surgery》2007,31(3):406-412
OBJECTIVE: The objective of this study is to evaluate the inflammatory response caused by endovascular stents in the treatment of aortic aneurysms. METHODS: Twenty-five patients underwent endovascular stent treatment from March through December 2005. The evolution of mediators (sedimentation velocity, C reactive protein, interleukin-6, interleukin-8, tumor necrosis factor-alpha, intercellular adhesion molecule-1, l-selectin), inflammatory cells (leukocytes, lymphocytes, platelets), serum creatinine and body temperature within preoperative period and in the following postoperative periods--1, 6, 24 and 48 h, 7 days, 1-3 months, was analyzed. In order to achieve statistic significance, Friedman test and Wilcoxon test were used, with index of significance of 5% (p<0.05). RESULTS: Peak values of sedimentation velocity, C reactive protein and interleukin-6 were observed at 7 days (p<0.0001), 48 h (p<0.0001) and 24h (p<0.0001), respectively. Tumor necrosis factor-alpha and interleukin-8 did not show statistically significant variability during the entire follow-up. In terms of intercellular adhesion molecule-1 and l-selectin, their expressive values were found in late phase of follow-up, although without statistical significance. Elevation of leukocytes count occurred in premature phase of follow-up (p<0.0001), while lymphocyte and platelet count occurred in a late phase of follow-up (p<0.0001). Serum levels of creatinine did not show significant variability during follow-up. The period between 24 and 48 h corresponded to major frequency for fever (p<0.0001). CONCLUSION: Individual mediators analysis and inflammatory cells demonstrated variability of their values during postoperative follow-up. This could help in the analysis of the inflammatory response evolution caused by endovascular stent treatment for aortic aneurysms in premature and late phases after implantation of the vascular prosthesis. 相似文献
25.
Carmelo Romano Michael A. Sesma Colin T. McDonald Karen O'malley Anthony N. van den Pol John W. Olney 《The Journal of comparative neurology》1995,355(3):455-469
The receptor mGluR5 is a metabotropic glutamate receptor with messenger RNA abundantly present throughout cortex, hippocampus, and caudate/putamen that is also coupled to phosphatidyl inositide hydrolysis and calcium mobilization. In this study, the distribution of mGluR5 was examined in rat brain by immunocytochemistry. The antibody utilized is highly specific and does not cross react with the most closely related other metabotropic glutamate receptor, as determined by Western blot analysis of nonneuronal cells transfected with metabotropic receptor coding sequences. The receptor mGluR5 is widely expressed with the highest density in olfactory bulb, caudate/putamen, lateral septum, cortex, and hippocampus, as confirmed with both immunocytochemistry and Western blot analysis. Electron microscopic studies in hippocampus and cortex indicate that the labeling is mostly on membranes of dendritic spines and shafts. Light and electron microscopic evidence indicates that some mGluR5 immunoreactivity is located in presynaptic axon terminals, suggesting that mGluR5 may function as a presynaptic receptor. 相似文献
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C Romano K Williams S DePriest R Seshadri G R Marshall M Israel P B Molinoff 《Molecular pharmacology》1992,41(4):785-792
Systematic series of monoamines, diamines, and triamines were used to define the structural requirements for interaction at the polyamine recognition site of the N-methyl-D-aspartate receptor complex. Effects of amines on binding of [3H]MK-801 to washed synaptic plasma membranes were measured in the presence of L-glutamate and glycine (100 microM each), in the absence or presence of spermine (10 microM). Linear aliphatic monoamines of methylene chain length up to 12 (dodecylamine) did not interact with the polyamine recognition site. Nonspecific inhibition of binding was observed at high concentrations of the longer monoamines. alpha,omega-Diamines of methylene chain length 2 (1,2-diaminoethane, DA2) through 12 (1,12-diaminododecane, DA12) had varying actions, depending on chain length. The shortest diamines (DA2 and DA3) acted as weak partial agonists, enhancing the binding of [3H[MK-801. Intermediate-length diamines (DA4-DA7) were selective polyamine antagonists, having little or no effect on binding of [3H]MK-801 measured in the absence of spermine but inhibiting binding measured in the presence of spermine. The longest diamines tested (DA8-DA12) acted as inverse agonists; they inhibited binding in the absence or presence of spermine, and this inhibition was blocked by the selective polyamine antagonist diethylenetriamine. Computer modeling of conformations of the diamines quantitatively documented that 1) these molecules are flexible and 2) long diamines may easily adopt conformations with inter-nitrogen distances mimicking those of short diamines. The cis and trans isomers of 1,4-diaminocyclohexane are inflexible, conformationally restricted diamines with markedly different actions. The cis isomer was a partial agonist and the trans isomer was an antagonist at the polyamine recognition site. Triamines of general structure NH2(CH2)3NH(CH2)xNH2 (TRI[3,x]), in which x = 3-12, were synthesized and tested for activity at the polyamine recognition site. Despite the large range of size, TRI[3,3] through TRI[3,9] were all fully polyamine agonists of similar potency. TRI[3,10] was a partial agonist, whereas TRI[3,12] inhibited binding of [3H]MK-801. Diethylenetriamine did not attenuate the effect of TRI[3,12]. Based on the results of the radioligand binding studies and the computer analysis, a model of the polyamine recognition site is proposed. 相似文献
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Deletion of the Major Proteolytic Site of the Helicobacter pylori Cytotoxin Does Not Influence Toxin Activity but Favors Assembly of the Toxin into Hexameric Structures 总被引:1,自引:0,他引:1
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Daniela Burroni Pietro Lupetti Cristina Pagliaccia Jean Marc Reyrat Romano Dallai Rino Rappuoli John L. Telford 《Infection and immunity》1998,66(11):5547-5550
The Helicobacter pylori cytotoxin is proteolytically cleaved at a flexible hydrophilic loop into two subunits. Deletion of the loop sequences had no effect on biological activity of the toxin in the HeLa cell vacuolation assay but favored the organization of the protein into hexameric rather than heptameric structures. 相似文献