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121.
J.P. Cano Y.C. Sumirtapura W. Cautreels Y. Sales 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1981,226(2):413-422
A gas chromatographic assay with electron-capture detection (GC—EC) is described for the metabolites of ethyl loflazepate (Victan), a new benzodiazepine with a potent anti-anxiety activity, in biological fluids. Since the parent drug undergoes a first-pass effect, pharmacokinetic data may only be obtained by measuring the total levels of two of the major metabolites. Accurate data can not be obtained for the metabolites separately since one of them (M1) is chemically transformed to the other (M2) during plasma sampling, storage and extraction.A sensitive, specific and accurate GC—EC assay is developed using a synthetic analogue of M2 as an internal standard. The limit of detection in plasma is approximately 2 ng/ml and the precision about 3% (within-run and between-run).The method is applied to plasma samples collected after oral administration of 2 mg and 4 mg of the drug in tablet form to human volunteers. The results obtained are correlated with those from an existing gas chromatographic—mass spectrometric assay. A very good correlation between the results (inter-laboratory comparison) is obtained, validating both techniques. 相似文献
122.
Block of outward current in cardiac purkinje fibers by injection of quaternary ammonium ions 总被引:6,自引:5,他引:1 下载免费PDF全文
We have studied the effects of iontophoretic injection of the quaternary ammonium compounds tetraethylammonium (TEA) and tetrabutylammonium (TBA) in cardiac purkinje fibers. We find that TBA(+) is a more effective blocker than TEA(+), but injection of either compound reduces the time-dependent outward plateau currents, transient outward current (I(to)), and the delayed rectifier (I(x)). Our findings provide evidence that these outward cardiac currents are carried by channels that in some respects are pharmacologically similar to squid axon potassium channels. We demonstrate that this procedure is a new tool that can be useful in the analysis of membrane currents in the heart. 相似文献
123.
Bruna Felício Milazzotto Maldonado Porchia Luana Raposo de Melo Moraes Aps Ana Carolina Ramos Moreno Jamile Ramos da Silva Maringela de Oliveira Silva Natiely Silva Sales Rubens Prince dos Santos Alves Clarissa Ribeiro Reily Rocha Matheus Molina Silva Karine Bitencourt Rodrigues Tcita Borges Barros Roberta Liberato Pagni Patrícia da Cruz Souza Mariana de Oliveira Diniz Luís Carlos de Souza Ferreira 《International journal of biological sciences》2022,18(1):15
The active immunotherapy concept relies on the use of vaccines that are capable of inducing antitumor immunity, reversion of the suppressive immunological environment, and long-term memory responses. Previously, antitumor vaccines based on a recombinant plasmid (pgDE7h) or a purified protein (gDE7) led to regression of early-established human papillomavirus (HPV)-associated tumors in a preclinical model. In this work, the anticancer vaccines were combined with cisplatin to treat HPV-induced tumors at advanced growth stages. The antitumor effects were evaluated in terms of tumor regression, induction of specific CD8+ T cells, and immune modulation of the tumor microenvironment. Acute toxicity induced by the treatment was measured by weight loss and histological alterations in the liver and kidneys. Our results revealed that the combination of cisplatin with either one of the tested immunotherapies (pgDE7h or gDE7) led to complete tumor regression in mice. Also, the combined treatment resulted in synergistic effects, particularly among mice immunized with gDE7, including activation of systemic and tumor-infiltrating E7-specific CD8+ T cells, tumor infiltration of macrophages and dendritic cells, and prevention of tumor relapses at different anatomical sites. Furthermore, the protocol allowed the reduction of cisplatin dosage and its intrinsic toxic effects, without reducing antitumor outcomes. These results expand our knowledge of active immunotherapy protocols and open perspectives for alternative treatments of HPV-associated tumors. 相似文献
124.
María Gabriela Lombardi María Pía Negroni Laura Tatiana Pelegrina María Ester Castro Gabriel L. Fiszman María Eugenia Azar Carlos Cresta Morgado María Elena Sales 《PloS one》2013,8(2)
The presence of autoantibodies in cancer has become relevant in recent years. We demonstrated that autoantibodies purified from the sera of breast cancer patients activate muscarinic acetylcholine receptors in tumor cells. Immunoglobulin G (IgG) from breast cancer patients in T1N0Mx stage (tumor size≤2 cm, without lymph node metastasis) mimics the action of the muscarinic agonist carbachol stimulating MCF-7 cell proliferation, migration and invasion. Angiogenesis is a central step in tumor progression because it promotes tumor invasion and metastatic spread. Vascular endothelial growth factor-A (VEGF-A) is the main angiogenic mediator, and its levels have been correlated with poor prognosis in cancer. The aim of the present work was to investigate the effect of T1N0Mx-IgG on the expression of VEGF-A, and the in vivo neovascular response triggered by MCF-7 cells, via muscarinic receptor activation. We demonstrated that T1N0Mx-IgG (10−8 M) and carbachol (10−9 M) increased the constitutive expression of VEGF-A in tumor cells, effect that was reverted by the muscarinic antagonist atropine. We also observed that T1N0Mx-IgG and carbachol enhanced the neovascular response produced by MCF-7 cells in the skin of NUDE mice. The action of IgG or carbachol was reduced in the presence of atropine. In conclusion, T1N0Mx-IgG and carbachol may promote VEGF-A production and neovascularization induced by breast tumor cells via muscarinic receptors activation. These effects may be accelerating breast tumor progression. 相似文献
125.
126.
The first Australian record of the lily thrips, Liothrips vaneeckei Priesner, is reported from a bulb farm in Warragul South, Victoria. It is an occasional pest of Lilium bulbs, both in the field and in storage, particularly in the USA and several European countries, and is also infrequently found in considerable numbers on the corms of orchids. 相似文献
127.
Ferreira EN Pires LC Parmigiani RB Bettoni F Puga RD Pinheiro DG Andrade LE Cruz LO Degaki TL Faria M Festa F Giannella-Neto D Giorgi RR Goldman GH Granja F Gruber A Hackel C Henrique-Silva F Malnic B Manzini CV Marie SK Martinez-Rossi NM Oba-Shinjo SM Pardini MI Rahal P Rainho CA Rogatto SR Romano CM Rodrigues V Sales MM Savoldi M da Silva ID da Silva NP de Souza SJ Tajara EH Silva WA Simpson AJ Sogayar MC Camargo AA Carraro DM 《Genetics and molecular research : GMR》2004,3(4):493-511
128.
Proteinase inhibitors are among the most promising candidates for expression by transgenic plants and consequent protection against insect predation. However, some insects can respond to the threat of the proteinase inhibitor by the production of enzymes insensitive to inhibition. Inhibitors combining more than one favorable activity are therefore strongly favored. Recently, a known small Kunitz trypsin inhibitor from Prosopis juliflora (PTPKI) has been shown to possess unexpected potent cysteine proteinase inhibitory activity. Here we show, by enzyme assay and gel filtration, that, unlike other Kunitz inhibitors with dual activities, this inhibitor is incapable of simultaneous inhibition of trypsin and papain. These data are most readily interpreted by proposing overlapping binding sites for the two enzymes. Molecular modeling and docking experiments favor an interaction mode in which the same inhibitor loop that interacts in a canonical fashion with trypsin can also bind into the papain catalytic site cleft. Unusual residue substitutions at the proposed interface can explain the relative rarity of twin trypsin/papain inhibition. Other changes seem responsible for the relative low affinity of PTPKI for trypsin. The predicted coincidence of trypsin and papain binding sites, once confirmed, would facilitate the search, by phage display for example, for mutants highly active against both proteinases. 相似文献
129.
Digitalis minor (Scrophulariaceae) is a cardenolide-producing plant endemic to the eastern Balearic Islands (Mallorca, Menorca, and Cabrera) that occurs in two morphologically distinct varieties: D. minor var. minor (pubescent) and D. minor var. palaui (glabrous). Levels and patterns of genetic diversity in 162 individuals from 17 D. minor populations across the entire geographic range were assessed using random amplified polymorphic DNA (RAPD) markers. Comigrating RAPD fragments tested were found to be homologous by Southern hybridization in both var. minor and var. palaui. To avoid bias in parameter estimation, analyses of population genetic structure were restricted to those RAPD bands that fulfilled the 3/N criterion (observed frequencies were less than 1 - [3/N] in each population) either among or within each island. Analyses of molecular variance (AMOVAs) with distances among individuals corrected for the dominant nature of RAPD (genotypic analysis) showed low values (1.57-17.55%) of between-population variability, indicating a relatively restricted population differentiation as expected for an outcrossing species such as D. minor. Nested AMOVAs demonstrated, however, a not significant partitioning of genetic diversity among Mallorca, Menorca, and Cabrera islands. Estimates of the Wright, Weir, and Cockerham and the Lynch and Milligan F(ST) from null allele frequencies corroborated AMOVA partitioning and provided evidence for population differentiation in D. minor. Our RAPD data did not show significant differences between pubescent and glabrous populations of D. minor, suggesting a failure to find a correlation between the RAPD loci and this morphological trait. 相似文献