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981.
Bacchi A Biemmi M Carcelli M Carta F Compari C Fisicaro E Rogolino D Sechi M Sippel M Sotriffer CA Sanchez TW Neamati N 《Journal of medicinal chemistry》2008,51(22):7253-7264
Previously, we synthesized a series of beta-diketo acid metal complexes as novel HIV-1 integrase (IN) inhibitors (J. Med. Chem. 2006, 46, 4248-4260). Herein, a further extension of this study is reported. First, detailed docking studies were performed in order to investigate the mode of binding in the active site of the free ligands and of their metal complexes. Second, a series of potentiometric measurements were conducted for two diketo acids chosen as model ligands, with Mn(2+) and Ca(2+), in order to outline a speciation model. Third, we designed and synthesized a new set of complexes with different stoichiometries and tested them in an in vitro assay specific for IN. Finally, we obtained the first X-ray structure of a metal complex with HIV-1 IN inhibition activity. Analysis of these results supports the hypothesis that the diketo acids could act as complexes and form complexes with the metal ions on the active site of the enzyme. 相似文献
982.
Marcella Zollino Christiane Zweier Ingrid D. Van Balkom David A. Sweetser Joseph Alaimo Emilia K. Bijlsma Jannine Cody Sarah H. Elsea Irina Giurgea Marina Macchiaiolo Robert Smigiel Ronald L. Thibert Ingrid Benoist Jill Clayton-Smith Channa F. De Winter Stijn Deckers Anusha Gandhi Sylvia Huisman Dagmar Kempink Frea Kruisinga Vittoria Lamacchia Giuseppe Marangi Leonie Menke Paul Mulder Ann Nordgren Alessandra Renieri Sue Routledge Carol J. Saunders Agnieszka Stembalska Hans Van Balkom Sandra Whalen Raoul C. Hennekam 《Clinical genetics》2019,95(4):462-478
983.
Tryptophan increases nocturnal rest and affects melatonin and serotonin serum levels in old ringdove
Paredes SD Terrón M Cubero J Valero V Barriga C Reiter RJ Rodríguez AB 《Physiology & behavior》2007,90(4):576-582
The sleep promoting functions of melatonin have gained wide scientific attention due to the ability of this indole to provide relief from sleep inefficiency and the temporal relationship between its nocturnal rise in the blood and the "opening of the sleep gate" at night. However, little is known about the effects exerted by its precursor, the amino acid tryptophan. We studied the effect of a 7-day administration of two concentrations of tryptophan (125 and 300 kg b.w.) on the activity/rest rhythms of ringdove, aged 2-3 (young) and 10-12 (old) years, and on the serum levels of serotonin and melatonin. Activity pulses were logged before, during, and up to 5 days after the treatments. The animals received 125 or 300 mg/kg b.w. per animal/day at 09:00 h or at 19:00 h. Subsequently we chose the treatment which gave the best results in terms of nocturnal rest without affecting diurnal activity, i.e., 300 mg/kg b.w. administered to old animals at 09:00 h, 1 h after lights on, for the serotonin and melatonin measurements. During this treatment, the nocturnal and diurnal levels and amplitudes of serotonin and melatonin were all significantly higher than the corresponding levels before and after the treatment. In sum, our results point to an improvement of nocturnal rest in this animal model of old ringdove when administering 300 mg/kg tryptophan 1 h after lights on. 相似文献
984.
Giovanni Corso Samuele Frassoni Antonia Girardi Elisa De Camilli Emilia Montagna Mattia Intra Luca Bottiglieri Alessandra Margherita De Scalzi Denise Mattar Fanianos Francesca Magnoni Alessandra Invento Antonio Toesca Fabio Conforti Vincenzo Bagnardi Giuseppe Viale Marco Angelo Colleoni Paolo Veronesi 《Journal of surgical oncology》2021,123(1):61-70
985.
Evaluation of the Receptor Activator of Nuclear Factor Kappa B Ligand (RANKL) Expression in Osteosarcoma and Its Association with the Clinicopathological Data 下载免费PDF全文
Hui Heng Chua Sharifah Emilia Tuan Sharif Wan Faisham Nu’man Wan Ismail Muhamad Syahrul Fitri Zawawi Sarimah Abdullah 《Asian Pacific journal of cancer prevention》2021,22(3):741-747
Background: The receptor activator of nuclear factor kappa B ligand (RANKL) is one of the key regulators of bone remodelling in bone oncology, including osteosarcoma. We assessed RANKL immunohistochemical expression in osteosarcoma, its association, and disease-free survival with the patients’ clinicopathological characteristics. Methods: One hundred osteosarcoma cases from 2003 to 2018 in Hospital Universiti Sains Malaysia were retrieved. The tissue samples were stained for RANKL, and the association with the clinicopathological characteristics was evaluated. Staining was interpreted in a semiquantitative scoring system and classified into negative and positive expressions. Results: Eighty-two cases had a positive expression of RANKL in which 56 and 26 patients were classified as low expression and high expression, respectively. The positive expression of RANKL did not show a significant association with clinicopathological characteristics. However, Kaplan Meier survival analysis showed a significant improvement in the disease-free survival patients who underwent limb salvage surgery (LSS) than amputated patients (p-value 0.002), whereas poorer survival was observed among conventional osteosarcomas compared to non-conventional osteosarcoma (p-value 0.01). Conclusion: Limb salvage surgery had proven to improve osteosarcoma patients’ survival compared to amputation, which could improve overall quality of life in osteosarcoma patients. However, our data did not show a significant association between positive RANKL immunohistochemistry with any of the clinicopathological characteristics and patients’ final survival. Further studies may be acquired to understand the suitability of using RANKL immunohistochemistry as prognostication in the management of osteosarcoma patients. 相似文献
986.
Danesi R Lupetti A Barbara C Ghelardi E Chella A Malizia T Senesi S Angeletti CA Del Tacca M Campa M 《The Journal of antimicrobial chemotherapy》2003,51(4):939-945
OBJECTIVES: The administration of antibacterial agents should be optimized on the basis of their distribution to enhance drug exposure and obtain bacterial eradication. This study examines the pharmacokinetics of azithromycin in plasma, lung tissue and bronchial washing in patients after oral administration of 500 mg versus 1000 mg once daily for 3 days. PATIENTS AND METHODS: Samples of plasma, lung tissue and bronchial washing were obtained from a cohort of 48 patients during open-chest surgery for lung resection up to 204 h after the last drug dose, and assayed for antibiotic concentrations. RESULTS: Azithromycin was widely distributed within the lower respiratory tract and sustained levels of the drug were detectable at the last sampling time in lung tissue. Doubling the dose of the antibiotic resulted in a proportional increase in lung area under the curve (AUC, 1245.4 versus 2514.2 h x mg/kg) and peak tissue concentration (Cmax, 8.93 +/- 2.05 versus 18.6 +/- 2.20 mg/kg). The pharmacodynamic parameter AUC/MIC for susceptible and intermediate strains of Streptococcus pneumoniae (MICs 0.5 and 2 mg/L, respectively) increased after administration of the 1000 mg schedule compared with 500 mg (AUC/MIC0.5 2414 versus 1144 and AUC/MIC2 2112 versus 814.1 h x mg/kg, respectively) in pulmonary tissue. CONCLUSIONS: Lung exposure to azithromycin is increased proportionally by doubling the dose, which results in a predictable pharmacokinetic behaviour of the drug in the lower respiratory tract. 相似文献
987.
Donicova Emilia Ramm L. Augsten R. Hammer M. 《Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie》2020,258(1):31-37
Graefe's Archive for Clinical and Experimental Ophthalmology - Retinal oxygen saturation (SO2) during flicker light stimulation was measured non-invasively in humans with age-related macular... 相似文献
988.
Klocperk Adam Friedmann David Schlaak Alexandra Emilia Unger Susanne Parackova Zuzana Goldacker Sigune Sediva Anna Bengsch Bertram Warnatz Klaus 《Journal of clinical immunology》2022,42(6):1254-1269
Journal of Clinical Immunology - Common variable immunodeficiency (CVID) is the most frequent symptomatic primary immunodeficiency, with heterogeneous clinical presentation. Our goal was to analyze... 相似文献
989.
In vitro activities of ravuconazole and four other antifungal agents against fluconazole-resistant or -susceptible clinical yeast isolates 总被引:3,自引:0,他引:3 下载免费PDF全文
Cuenca-Estrella M Gomez-Lopez A Mellado E Garcia-Effron G Rodriguez-Tudela JL 《Antimicrobial agents and chemotherapy》2004,48(8):3107-3111
The activities of ravuconazole and four other antifungal agents were tested against a collection of 1,796 clinical yeast isolates, including fluconazole-susceptible and -resistant strains. Ravuconazole was active against the majority of fluconazole-resistant isolates; but for 102 of 562 (18%) resistant isolates, mainly Candida tropicalis, Candida glabrata, and Cryptococcus neoformans, ravuconazole MICs were > or =1 microg/ml. 相似文献
990.