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排序方式: 共有3219条查询结果,搜索用时 15 毫秒
31.
32.
Valentina Mazzotta Alessandro Cozzi Lepri Francesca Colavita Silvia Rosati Eleonora Lalle Claudia Cimaglia Jessica Paulicelli Ilaria Mastrorosa Serena Vita Lavinia Fabeni Alessandra Vergori Gaetano Maffongelli Fabrizio Carletti Simone Lanini Emanuela Caraffa Eugenia Milozzi Raffaella Libertone Pierluca Piselli Enrico Girardi AnnaRosa Garbuglia Francesco Vaia Fabrizio Maggi Emanuele Nicastri Andrea Antinori INMI COVID- Outpatient Treatment Study Group 《Journal of medical virology》2023,95(1):e28186
33.
Angela Bachi Raffaella Brambilla Roberto Fanelli Roberto Bianchi Ettore Zuccato Chiara Chiabrando 《British journal of pharmacology》1997,121(8):1770-1774
- 8-epi-prostaglandin (PG) F2α, a major F2 isoprostane, is produced in vivo by free radical-dependent peroxidation of lipid-esterified arachidonic acid. Both cyclo-oxygenase isoforms (COX-1 and COX-2) may also form free 8-epi-PGF2α as a minor product. It has been recently seen in human volunteers that the overall basal formation of 8-epi-PGF2α in vivo is mostly COX-independent and urinary 8-epi-PGF2α is therefore an accurate marker of ‘basal'' oxidative stress in vivo.
- To test the validity of this marker in the rat, we evaluated in vivo the effect of COX inhibition on the formation of 8-epi-PGF2α vs prostanoids. Two structurally unrelated COX inhibitors (naproxen: 30 mg kg−1 day−1; indomethacin: 4 mg kg−1 day−1) were given i.p. to rats kept in metabolic cages. In vivo formation of 8-epi-PGF2α was assessed by measuring its urinary excretion. Prostanoid biosynthesis was assessed by measuring urinary excretion of major metabolites of thromboxane (TX) and prostacyclin (2,3-dinor-TXB1 and 2,3-dinor-6-keto-PGF1α). All compounds were selectively measured by immunopurification/gas chromatography-mass spectrometry.
- Naproxen reduced urinary excretion of 2,3-dinor-TXB1 and 2,3-dinor-6-keto-PGF1α but, unexpectedly, also that of 8-epi-PGF2α (82, 49 and 52% inhibition, respectively). Indomethacin had a similar effect (77, 69 and 55% inhibition). Esterified 8-epi-PGF2α in liver and plasma remained unchanged after indomethacin.
- These findings prompted us to re-assess the contribution of COX activity to the systemic production of 8-epi-PGF2α in man. We gave naproxen (1 g day−1) to healthy subjects (four nonsmokers and four smokers). Urinary 8-epi-PGF2α remained unchanged in the two groups (9.63±0.99 before vs 10.24±1.01 after and 20.14±3.00 vs 19.03±2.45 ng h−1 1.73 m−2), whereas there was a marked reduction of major urinary metabolites of thromboxane and prostacyclin (about 90% for both 11-dehydro-TXB2 and 2,3-dinor-TXB2; >50% for 2,3-dinor-6-keto-PGF1α).
- To investigate whether rat COX-1 produces 8-epi-PGF2α more efficiently than human COX-1, we measured the ex vivo formation of 8-epi-PGF2α and TXB2 simultaneously in whole clotting blood. Serum levels of 8-epi-PGF2α and TXB2 were similar in rats and man.
- We conclude that a significant amount of COX-dependent 8-epi-PGF2α is present in rat but not in human urine under normal conditions. This implies that urinary 8-epi-PGF2α cannot be used as an index of near-basal oxidant stress in rats. On the other hand, our data further confirm the validity of this marker in man.
34.
Gurmeet Kaur Dorina Belotti Angelika M Burger Kirsten Fisher-Nielson Patrizia Borsotti Elena Riccardi Jagada Thillainathan Melinda Hollingshead Edward A Sausville Raffaella Giavazzi 《Clinical cancer research》2004,10(14):4813-4821
PURPOSE: The purpose of this study was to investigate the antiangiogenic properties of 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG; NSC707545), a water-soluble benzoquinone ansamycin. EXPERIMENTAL DESIGN: The activity of 17-DMAG, in vivo, was evaluated for inhibition of fibroblast growth factor (FGF)-2-induced angiogenesis in s.c. implanted Matrigel in mice. In vitro, the activity of 17-DMAG on endothelial cells (human umbilical vein endothelial cells; HUVEC) was tested in FGF-2; and vascular endothelial growth factor (VEGF)-induced proliferation and apoptosis, motility, and extracellular matrix invasion; and on the alignment of capillary like structures in Matrigel. The protein level of heat shock protein (Hsp)90 and client proteins was examined by Western blot in FGF-2 and VEGF-stimulated HUVEC. RESULTS: Daily oral administration of 17-DMAG affected the angiogenic response in Matrigel in a dose-dependent manner. The hemoglobin content in the Matrigel implants was significantly inhibited, and the histological analysis confirmed a decrease of CD31(+) endothelial cells and of structures organized in cord and erythrocyte-containing vessels. In vitro, the compound inhibited dose-dependently the migration and the extracellular matrix-invasiveness of HUVEC and their capacity to form capillary like structures in Matrigel. 17-DMAG treatment also inhibited FGF-2 and VEGF-induced HUVEC proliferation and resulted in apoptosis. Accordingly, the expression of Hsp90 direct client proteins (pAkt and c-Raf-1) or their downstream substrates including pERK was also affected. 17-DMAG consistently increased the expression of Hsp70. Throughout the study similar results were obtained with 17-allylamino-17-demethoxygeldanamycin (17-AAG; NSC330507), the analog compound currently undergoing clinical trials. CONCLUSIONS: We show that the Hsp90 targeting agents 17-DMAG and 17-AAG inhibit angiogenesis. The strong effects on endothelial cell functions, in vitro, indicate that the antiangiogenic activity of 17-DMAG/17-AAG could also be due to a direct effect on endothelial cells. The oral bioavailability of 17-DMAG might be of advantage in investigating the potential of this compound in clinical trials with antiangiogenic as well as antiproliferative endpoints. 相似文献
35.
Cyclosporin A in the ocular fluids of uveitis patients following long-term systemic administration 总被引:1,自引:0,他引:1
Paolo Mora Uta Ceglarek Francesca Manzotti Laura Zavota Arturo Carta Raffaella Aldigeri Jelka G. Orsoni 《Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie》2008,246(7):1047-1052
BACKGROUND/AIMS: To determine the levels of cyclosporin A (CsA) in tears and the anterior segment of the eye following long-term oral intake for autoimmune diseases. METHODS: Subjects taking oral CsA to treat relapsing autoimmune ocular inflammation were included in this study. All of the patients had been quiescent for at least 6 months. In patients scheduled for cataract extraction (group A), the CsA levels in the blood, aqueous humour and anterior capsule of the lens were determined. In subjects not requiring surgical intervention (group B), CsA was measured in tears and blood. The samples were analysed using turbulent flow chromatography coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: There were 19 subjects in group A and 43 subjects in group B. CsA was detectable in all of the tear samples with a mean value of 22.4 +/- 20.2 ng/ml and there was a significant positive correlation between the CsA levels in tears and blood (P = 0.012). CsA was not detected in any of the surgical samples. CONCLUSION: LC-MS/MS proved very sensitive for detecting CsA in low-volume biological samples. CsA was present in human tears in proportion to the blood level after an average of 12 hours from the last oral intake. 相似文献
36.
Targeting of the tumor stroma, including the tumor vasculature, represents a new frontier in the treatment of malignancy.
Preclinical studies and clinical experiences have established that stroma-directed novel agents must be combined with conventional
therapies in order to achieve relevant therapeutic efficacy. Here we review our preclinical experience on combinations of
paclitaxel with a tyrosine kinase receptor inhibitor of angiogenesis (SU6668) and a vascular disrupting agent (VDA, ZD6126),
and discuss the critical factors that determine the outcome of these treatments. We also analyze the relevance of the intrinsic
sensitivity of the tumor to the drugs, as well as the possibility that the two combined agents synergistically affect the
vasculature or independently target the host and the tumor compartments. Finally, we discuss the need to carefully optimize
scheduling and sequencing, through the use of reliable end points, in order to avoid negative pharmacological interactions
and to improve the antineoplastic efficacy of paclitaxel-based combination treatments. 相似文献
37.
The transformation of aliphatic and aromatic acids to their corresponding alcohols, involving two reductive steps, is difficult to perform biologically due to its low redox potential. For this reason, the reduction of nonactivated carboxylic acids has been described for only a limited number of substrates and confined to a few microbial groups (fungi, clostridia, and archea). Nine species of cultured plant cells were able to reduce cinnamic, hexanoic, and octanoic acids to the corresponding primary alcohols with yields ranging from 2 to 80% (w/w). Aldehyde was detected only for three species during the reduction of cinnamic acid, confirming that the second reductive step from aldehyde to alcohol is faster than the first, from acid to aldehyde. Lyophilized cells from some of the cultures were used in buffer and solvent-water systems to obtain the reduction of carbonylic (ethyl acetoacetate) and carboxylic (cinnamic and hexanoic acids) groups. 相似文献
38.
Paradisi R Fabbri R Battaglia C Facchinetti F Venturoli S 《Fertility and sterility》2007,88(3):744-748
The aim of this study was to evaluate the systemic production of nitric oxide (NO) in missed and threatened abortion and in nonpregnant and regular pregnant controls with the purpose of defining its role in the mechanisms regulating the first-trimester pregnancy toward either positive or negative evolution. Patients with missed abortion showed serum NO levels clearly decreased compared with nonpregnant patients and patients with regular pregnancy and threatened abortion, supporting a direct functional role of the NO mediator in early embryonic development and confirming its importance in the uterus and cervix during abortion. 相似文献
39.
Scioscia M Vimercati A Maiorano A Depalo R Selvaggi L 《European journal of obstetrics, gynecology, and reproductive biology》2007,130(1):60-65
BACKGROUND: Perinatal mortality rate is used as an indicator of reproductive health worldwide. In western countries, national mortality registers are usually accurate and reliable. METHODS AND AIMS: We reviewed the data recorded in the past 50 years in Italy on perinatal and infant mortality. Each single class of mortality rate (according to WHO definitions) was assessed on temporal trends allowing a critical speculative analysis, mainly focusing on the last 20 years, in an attempt to evaluate the impact of prenatal diagnosis. RESULTS: Infant mortality rate (IMR) constantly decreased in the study period whereas early neonatal mortality rate progressively diminished in a 5-year comparison till the early 1990s. Perinatal mortality showed a linear negative trend until the 1980s, after which the decrease steadied at about 23% in the following 5-year period. Infant mortality attributable to congenital anomalies throughout a 20-year span (1980-2000) was steady at about 23% although a progressive reduction in general infant mortality was reported. CONCLUSIONS: A higher reduction in neonatal and perinatal mortality rate was found before the wide availability of the ultrasonographic prenatal diagnosis and the introduction of the law on voluntary abortion in Italy. Given these data, it seems that advances in neonatal care have improved the infant survival rates more than prenatal diagnosis, whereas obstetric care is linked to a reduction of the early perinatal mortality rate. 相似文献
40.
Gennaro Daniele Clorinda Schettino Laura Arenare Domenico Bilancia Fabio Farinati Piera Federico Stefano Tamberi Gino Crivellari Sandro Barni Raffaella Tortora Francesco Izzo Antonio Frassoldati Luigi Cavanna Claudia Mucciarini Luigi Bolondi Angelo Dinota Filippo Pelizzaro Maria Carmela Piccirillo Piera Gargiulo Massimo Di Maio Ciro Gallo Francesco Perrone Bruno Daniele 《肝癌研究(英文版)》2021,7(7):52-65
Aim: Only patients with good liver function {[Child-Pugh (CP)] A class} were eligible for trials testing sorafenib as first-line treatment of hepatocellular car... 相似文献