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排序方式: 共有40条查询结果,搜索用时 46 毫秒
1.
Ferraiolo Bobbe L. Winslow John Laramee Gary Celniker Abbie Johnston Paul 《Pharmaceutical research》1991,8(8):1032-1038
Two forms of chemically synthesized human relaxin (hRlx and hRlx-2) were administered as 88 µg/kg intravenous bolus doses to pregnant and nonpregnant rhesus monkeys. No significant differences in pharmacokinetics were observed between pregnant and nonpregnant animals for either form of relaxin; however, clearance of hRlx (3.1–3.4 ml/min/kg) was significantly slower than clearance of hRlx-2 (6.2–6.5 ml/min/kg) in both pregnant and nonpregnant animals. Although the terminal half-lives for hRlx and hRlx-2 were similar (148–157 min), the initial and steady-state volumes of distribution were somewhat larger for hRlx-2 (71–85 and 398–418 ml/kg, respectively) than for hRlx (61–65 and 294–319 ml/kg, respectively). The metabolism of hRlx-2 was also investigated in pregnant and non-pregnant rhesus monkeys after iv bolus (0.44 mg/kg) or 60-min infusion (1.1 mg/kg) administration. Fast atom bombardment mass spectral analysis of the relaxin immunoreactivity isolated from the plasma indicated that hRlx-2 was partially degraded by removal of amino acids from the C terminus of the B chain. The percentage of intact material declined over a 60-min time course. At 60 min post-dose, intact hRlx-2 was 46–64% of the detected material. Degraded forms representing loss of one and four amino acids (hRlx) from the C terminus of the B chain were 11–13 and 19–34% of the detectable material, respectively. 相似文献
2.
Plasma clearance and tissue distribution of labelled insulin-like growth factor-I (IGF-I), IGF-II and des(1-3)IGF-I in rats 总被引:1,自引:0,他引:1
F J Ballard S E Knowles P E Walton K Edson P C Owens M A Mohler B L Ferraiolo 《The Journal of endocrinology》1991,128(2):197-204
Incubation of 125I-labelled insulin-like growth factor-I (IGF-I) with rat plasma at 4 degrees C led to the transfer of approximately half the radioactivity to 150 kDa and smaller complexes with IGF-binding proteins. The extent of association was greater with labelled IGF-II and essentially absent with the truncated IGF-I analogue, des(1-3)IGF-I. A greater degree of binding of IGF peptides with binding proteins occurred after i.v. injection of the tracers into rats, but most of the des(1-3)IGF-I radioactivity remained free. Measurement of the total plasma clearances showed the rapid removal of des(1-3)IGF-I compared with IGF-I and IGF-II; the mean clearances were 4.59, 1.20 and 1.34 ml/min per kg respectively. The mean steady-state volume of distribution was larger for des(1-3)IGF-I than for IGF-I and IGF-II (461, 167 and 181 ml/kg respectively), probably because of the differences in plasma protein binding. With all tracers, radioactivity appeared in the kidneys to a greater extent than in other organs. The amount of radioactivity found in the adrenals, brain, skin, stomach, duodenum, ileum plus jejunum and colon was in rank order, des(1-3)IGF-I greater than IGF-I greater than IGF-II. Since this ranking is the opposite of the abilities of the three IGF peptides to form complexes with plasma binding proteins, we propose that the plasma binding proteins inhibit the transfer of the growth factors to their tissue sites of action. Moreover, we suggest that IGF analogues that are cleared rapidly from blood may have greater biological potencies in vivo. 相似文献
3.
The contamination by nitrous oxide of an operating room atmosphere was studied in a number of experiments, in the absence of personnel and using a gaschromatographic method. The evacuating device of the anesthesia machine proved to be ineffective to overcome the hazard of leaks in the breathing system, whereas the air conditioning flow rates (12 outside air changes per hour) minimized waste anesthetic gas concentrations. 相似文献
4.
Interspecies Scaling of Clearance and Volume of Distribution Data for Five Therapeutic Proteins 总被引:3,自引:0,他引:3
Mordenti Joyce Chen Sharon A. Moore Jerome A. Ferraiolo Bobbe L. Green James D. 《Pharmaceutical research》1991,8(11):1351-1359
The clearance and volume of distribution of five human proteins (recombinant CD4, CD4 immuno-globulin G, growth hormone, tissue-plasminogen activator, and relaxin) in humans and laboratory animals were analyzed as a function of body weight using allometric scaling techniques. These proteins cover a 16-fold range of molecular weight (6 to 98 kD), are produced by recombinant or synthetic methods, and may be cleared by different mechanisms. The analyses revealed that the clearance and volume data for each protein were satisfactorily described by an allometric equation (Y = a Wb). The allometric exponent (b) for clearance (ml/min) ranged from 0.65 to 0.84, the allometric exponent for the initial volume of distribution (ml) ranged from 0.83 to 1.05, and the allometric exponent for the volume of distribution at steady state (ml) ranged from 0.84 to 1.02. Exponent values from 0.6 to 0.8 for clearance and 0.8 to 1.0 for volumes are frequently cited for small molecules and are expected based on empirical interspecies relationships. When the preclinical data were analyzed separately, the pre-clinical allometric relationships were usually predictive of the human results. These findings indicate that the clearance and volume of distribution of select biomacromolecules follow well-defined, size-related physiologic relationships, and preclinical pharmacokinetic studies provide reasonable estimates of human disposition. Employing this methodology during the early phases of drug development may provide a more rational basis for dose selection in the clinical environment. 相似文献
5.
Erika Martinelli Giulia Martini Claudia Cardone Teresa Troiani Giuseppina Liguori Donata Vitagliano Stefania Napolitano Floriana Morgillo Barbara Rinaldi Rosa Marina Melillo Federica Liotti Anna Nappi Roberto Bianco Liberato Berrino Loreta Pia Ciuffreda Davide Ciardiello Vincenzo Iaffaioli Gerardo Botti Fiorella Ferraiolo Fortunato Ciardiello 《Oncotarget》2015,6(27):23281-23296
AXL is a tyrosine kinase receptor activated by GAS6 and regulates cancer cell proliferation migration and angiogenesis. We studied AXL as new therapeutic target in colorectal cancer (CRC). Expression and activation of AXL and GAS6 were evaluated in a panel of human CRC cell lines. AXL gene silencing or pharmacologic inhibition with foretinib suppressed proliferation, migration and survival in CRC cells. In an orthotopic colon model of human HCT116 CRC cells overexpressing AXL, foretinib treatment caused significant inhibition of tumour growth and peritoneal metastatic spreading. AXL and GAS6 overexpression by immunohistochemistry (IHC) were found in 76,7% and 73.5%, respectively, of 223 human CRC specimens, correlating with less differentiated histological grading. GAS6 overexpression was associated with nodes involvement and tumour stage. AXL gene was found amplified by Fluorescence in situ hybridization (FISH) in 8/146 cases (5,4%) of CRC samples.Taken together, AXL inhibition could represent a novel therapeutic approach in CRC. 相似文献
6.
7.
LaBrie JW Thompson AD Ferraiolo P Garcia JA Huchting K Shelesky K 《Addictive behaviors》2008,33(2):266-278
The Relational Health Indices (RHI) is a relatively new measure that assesses the strength of relationships. It has been found that relational health has a protective factor for women, such that it enhances positive experiences and limits negative ones. The current study is the first to use the RHI to examine the effect of relational health on alcohol consumption and alcohol consequences. First year college women were given questionnaires assessing relational health, drinking motives, and alcohol use in their first few months at a mid-sized, private university. Due to the social nature of college settings, it was predicted that relational health would moderate the relationship between motives and alcohol consumption. Further, due to the protective factor of relational health, it was predicted that relational health would attenuate the relationship between drinking and negative consequences. These hypotheses were supported. Relational health, moderated the relationship between both social and coping drinking motives and drinking, such that women with strong relational health towards their peers and community who also had high social and coping motives, drank more than those with weaker relationships. Paradoxically, relational health also moderated the relationship between drinking and consequences such that heavy drinking women with strong relational health experienced fewer negative consequences than women with weaker relational health. Results indicate that although relational health is associated with an increase in alcohol consumption, it may also serve as a protective factor for alcohol-related negative consequences. Future research and interventions may seek to de-link the relational health-drinking connection in the college student environment. 相似文献
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10.
B L Ferraiolo M M Halldin Y Asscher Y Akita K L Melmon L Z Benet N Castagnoli 《Pharmacology》1987,34(2-3):157-166
beta-Adrenergic agonist analogs (congeners) of isoproterenol in which the N-isopropyl group has been linked to a p-methyl- (119) or p-trifluoromethyl- (143) anilide moiety through a four carbon methylene spacer have been investigated with respect to their plasma pharmacokinetic profiles and biliary and urinary elimination characteristics in rats. In spite of the differences in selectivity of pharmacologic effects and durations of action between these unique beta-adrenergic agonists and isoproterenol, no differences were observed in their pharmacokinetic parameters in plasma after intravenous administration. Plasma clearances were rapid (67-78 ml/min) and the compounds were widely distributed. In contrast to the known elimination characteristics of isoproterenol, biliary excretion was the major pathway for elimination of 119 and 143. Parent drug and 'one' major metabolite peak appeared in HPLC chromatograms of bile collected from rats that received 119 and 143 by intravenous administration. Preliminary evidence suggests that this metabolite peak consists of one or more glucuronide and/or sulfate conjugates. Urinary excretion appears to be of lesser quantitative importance for 119 and 143 than for isoproterenol. The protracted duration of residence of the derivatives in the heart may help to explain the unusual effects and tissue-specific pharmacological properties of these unique beta-adrenergic agonists. 相似文献