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Dr. Vera J.S. Van de Velde Ph.D. Dr. Achiel P. Van Peer Ph.D. Dr. Joseph J.P. Heykants Ph.D. Mr. Robert J.H. Woestenborghs Chem. Eng. Dr. Patricia Van Rooy M.D. Mr. Karel L. De Beule Dip. Hosp. Pharm. Dr. Geert F.M.J. Cauwenbergh Ph.D. 《Pharmacotherapy》1996,16(3):424-428
Study Objective . To compare the pharmacokinetics of a single 100-mg oral dose of itraconazole administered as 10 ml of a 10-mg/ml itraconazole solution in hydroxypropyl-β-cyclodextrin under fasting versus postprandial conditions. Design . Open-label, two-way, randomized, crossover study. Setting . Janssen Research Foundation, Belgium. Patients . Twelve healthy volunteers. Interventions . Blood samples were obtained for pharmacokinetic analyses immediately before dosing and at regular intervals up to 96 hours after each dose. Blood and urine samples were obtained for hematologic, biochemical, and urinary safety analyses at baseline and at the end of the study. Measurements and Main Results . The mean peak plasma concentrations of both itraconazole and its active metabolite hydroxy-itraconazole were significantly higher under fasting conditions than under postprandial conditions. The mean times to peak concentration for both the parent compound and its metabolite were significantly shorter under fasting than under nonfasting conditions. The mean areas under the curve (AUC0–∞ and AUC0–24 hrs) were also significantly higher under fasting than under postprandial conditions. Conclusions . Our findings suggest that the higher bioavailability of this new formulation of itraconazole may be of benefit in seriously ill patients who are not able to ingest adequate quantities of food. The fact that the solution was also well tolerated and was not associated with clinically significant changes in any laboratory value further underscores the potential utility of this dosing form. 相似文献
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N N Trapeznikov V A Gorbunova L A Er?mina P A Siniukov E E Kovalevski? 《Voprosy onkologii》1987,33(7):65-74
The effectiveness of cis-diammine-dichloroplatinum (cisplatinum, platidiam, DDP) alone or as a component of combined treatment was evaluated in 85 patients with osteogenic sarcoma. The said drugs were used as adjuvants following radical surgery (group I-18 cases), in combined treatment of solitary and single lung metastases (group 2-7 cases) and in 60 patients with advanced tumors (group 3). An analysis of long-term results showed response in 30.8% in group 3. In group 2, application of chemotherapy plus surgery was followed by remissions of 2-46+-month duration (mean-13.9 months). In group I, 78.7% are expected to survive metastasis-free more than 12 months. Toxicity was moderate, with nausea and vomiting (87.1%), myelosuppression (52.8%), nephrotoxicity (48.6%) and alopecia (75.7%) being the most common side-effects. 相似文献
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Vera Moliadze Dimitrios Giannikopoulos Ulf T. Eysel Klaus Funke 《The Journal of physiology》2005,566(3):955-965
In this study, we tested the paired-pulse transcranial magnetic stimulation (ppTMS) protocol – a conditioning stimulus (CS) given at variable intervals prior to a test stimulus (TS) – for visually evoked single-unit activity in cat primary visual cortex. We defined the TS as being supra-threshold when it caused a significant increase or decrease in the visually evoked activity. By systematically varying the interstimulus interval (ISI) between 2 and 30 ms and the strength of CS within the range 15–130% of TS, we found a clear dependence of the ppTMS effect on CS strength but little relation to ISI. The CS effect was strongest with an ISI of 3 ms and steadily declined for longer ISIs. A switch from enhancement of intracortical inhibition at short ISIs (2–5 ms, SICI) to intracortical facilitation (ICF) at longer ISIs (7–30 ms), as demonstrated for human motor cortex, was not evident. Whether the CS caused facilitation or suppression of the TS effect mainly depended on the strength of CS and the polarity of the TS effect: within a range of 60–130% a positive correlation between ppTMS and TS effect was evident, resulting in a stronger facilitation if the TS caused facilitation of visual activity, and more suppression if the TS was suppressive by itself. The correlation inverted when CS was reduced to 15–30%. The ppTMS effect was not simply the sum of the CS and TS effect, it was much smaller at weak CS strength (15–50%) but stronger than the sum of CS and TS effects at CS strength 60–100%. Differences in the physiological state between sensory and motor cortices and the interactions of paired synaptic inputs are discussed as possible reasons for the partly different effects of ppTMS in cat visual cortex and human motor cortex. 相似文献
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Genetic mapping ofPim-1 putative oncogene to mouse chromosome 17 总被引:10,自引:0,他引:10
John Hilkens H. Theo Cuypers Gerard Selten Vera Kroezen Jo Hilgers Anton Berns 《Somatic Cell and Molecular Genetics》1986,12(1):81-88
Pim-1 is a putative oncogene activated in T-cell lymphomas induced by Moloney and AKR mink cell focus forming (MCF) viruses. We have determined the chromosomal localization of the Pim-1gene in mice by Southern blot analysis of DNAs obtained from a panel of mouse-Chinese hamster somatic cell hybrids. The Pim-1gene was localized on chromosome 17, a chromosome frequently aberrant in T-cell lymphomas. Two chromosomal regions, containing sequences homologous to regions within the Pim-1locus, were localized on chromosome 6 and 16. 相似文献
28.
The E5 proteins of bovine papillomavirus type 1 (BPV-1) and human papillomavirus type 16 (HPV-16) are small (44-83 amino acids), hydrophobic polypeptides that localize to membranes of the Golgi apparatus and endoplasmic reticulum, respectively. While the oncogenic properties of BPV-1 E5 have been characterized in detail, less is known about HPV-16 E5 due to its low expression in mammalian cells. Using codon-optimized HPV-16 E5 DNA, we have generated stable fibroblast cell lines that express equivalent levels of epitope-tagged BPV-1 and HPV-16 E5 proteins. In contrast to BPV-1 E5, HPV-16 E5 does not activate growth factor receptors, phosphoinositide 3-kinase or c-Src, and fails to induce focus formation, although it does promote anchorage-independent growth in soft agar. These variant activities are apparently unrelated to differences in intracellular localization of the E5 proteins since retargeting HPV-16 E5 to the Golgi apparatus does not induce focus formation. 相似文献
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Scientific information regarding plants used in folk medicine in the form of teas and their effect on human health or on genetic material has been the subject of many different types of investigation. The antimutagenic activity of two plants Maytenus ilicifolia and Peltastes peltatus, both rich in compounds of the flavonoid and tannin groups and frequently employed in folk medicine, was studied. Antimutagenicity was determined against known mutagenic substances (4-oxide-1-nitroquinoline, sodium azide, 2-nitrofluorene, aflatoxin B(1), 2-aminofluorene and 2-aminoanthracene), using the Salmonella/microsome assay. Infusions of P.peltatus showed high cytotoxicity and a co-mutagenic effect for induction of base pair substitution mutations with 4-oxide-1-nitroquinoline (-S9 mix). Infusions of M.ilicifolia produced similar effects for frameshift and base pair substitution mutations. With the mutagens 2-nitrofluorene (TA98) and sodium azide (TA100) no significant enhancement effects (co-mutagenic effects) were observed and inhibition of mutagenic activity and cytotoxicity were also diminished. In assays evaluating antimutagenic activity in the presence of metabolic activation utilizing S9 mix, high and significant inhibition of aflatoxin B(1)-, 2-aminofluorene- and 2-aminoanthracene-induced mutagenicity was observed in the presence of the infusions using both TA98 and TA100 and employing doses ranging from 25 to 500 mg/plate. Seventy-five percent of the doses tested exhibited a significant or suggestive decrease in induced mutagenicity with the infusion of M.ilicifolia. With the infusion of P.peltatus significant or suggestive antimutagenic responses were observed with 50% of the doses evaluated. Complexity was clearly noted in the responses observed in the interaction of aqueous extracts of M.ilicifolia and P.peltastes with the genetic material and metabolites generated by the S9 mix played an important role in the protection of DNA. 相似文献