Abstract：
:A method to evaluate interactions between biologically active agents is presented. Synergism, zero interaction, and antagonism were easily detected with the three-dimensional approach proposed herein. This method is compatible with a checkerboard design to diagnose the interaction between agents and obviate the need to test their mixtures in a fixed concentration ratio as proposed by Chou and Talalay. Dose-response curves for individual agents were obtained, and experimental data fitted to appropriate equations by nonlinear regression. If zero interaction was present, the predicted effect could be calculated for each combination using the classical isobole equation with any spreadsheet having a command to solve mathematical equations by iteration. This allowed the selection of appropriate concentrations for the combination of two or more agents. Interaction between agents could be assessed in two ways: by comparing experimental with expected effects, if zero interaction is present; or by analyzing the reduction or increase in total dose found as a consequence of the interaction. The applicability of both approaches is discussed and, for purposes of comparison with other methods, examples based on published data are analyzed and commented upon.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Martinez-Irujo JJ,Villahermosa ML,Alberdi E,Santiago Edoi
10.1016/s0006-2952(95)02230-9subject
Has Abstractpub_date
1996-03-08 00:00:00pages
635-44issue
5eissn
0006-2952issn
1873-2968pii
S0006-2952(95)02230-9journal_volume
51pub_type
杂志文章abstract：:The normal sexual dimorphism in murine hepatic hexobarbital metabolism (i.e. females greater than males) was found to be absent in senescent animals. Hexobarbital metabolism, expressed as microsomal activity of hexobarbital hydroxylase and hexobarbital-induced sleep time, in senescent male mice was similar to that in ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(88)90724-1
更新日期：1988-01-15 00:00:00
abstract：:Oxyntomodulin (Oxm) is a hormone which has been shown to exhibit a range of potentially beneficial actions for alleviation of obesity-diabetes. However, exploitation of Oxm-based therapies has been severely restricted due to degradation by the enzyme dipeptidylpeptidase-IV (DPP-IV). Thus, the aim of this study was to ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2010.08.010
更新日期：2010-12-01 00:00:00
abstract：:Sepsis is a complex clinical syndrome that results from a harmful host response to infection, in which foreign bacteria and lipopolysaccharide (LPS) are potent activators of different immune cells, including monocytes and macrophages. To date, there are currently few effective adjuvant therapies in clinical use except...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2005.04.040
更新日期：2005-07-15 00:00:00
abstract：:The in vivo actions of two antimetabolites, acivicin (NSC-163501) and tiazofurin (NSC-286193), were examined on the enzymic programs of rat bone marrow. From the bone marrow of the femurs, 100,000 g supernatant fractions were prepared; enzymic activities were measured by isotopic assays, and cellularity was determined...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(88)90175-x
更新日期：1988-03-01 00:00:00
abstract：:Reoxygenation of hypoxic (120 min at 37 degrees) rabbit kidney cortical slices in vitro resulted in a rapid increase in lipid peroxidation and phosphatidylinositol hydrolysis. No changes in phosphatidylinositol breakdown occurred during hypoxia or upon reoxygenation in the absence of calcium. Incubation of renal slice...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(93)90002-e
更新日期：1993-05-25 00:00:00
abstract：:Invasion of normal brain tissue by tumor cells is a major contributing factor to the recurrence of glioblastoma and its resistance to therapy. Here, we have assessed the efficacy of the microtubule (MT) targeting agent Epothilone B (patupilone) on glioblastoma cell migration, a prerequisite for invasive tumor cell beh...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2012.05.010
更新日期：2012-08-15 00:00:00
abstract：:Rat aortic smooth muscle cells in culture (A-10; ATCC CRL 1476) exhibited low levels of beta-adrenergic receptors as determined by specific binding of [125I]cyanopindolol ([125I]CYP) and marginal stimulation of adenylate cyclase in plasma membranes by (-)isoproterenol. When these cells were exposed to 5 mM sodium buty...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(86)90669-6
更新日期：1986-11-01 00:00:00
abstract：:The participation of mitochondria in the mechanism of tumor cell death induced by non-steroid anti-inflammatory drugs is uncertain. Here we show that ibuprofen induces death of Walker 256 tumor cells independently on mitochondrial depolarization as estimated by flow cytometry using DioC(6)(3). Oligomycin increased mit...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2004.08.006
更新日期：2004-12-01 00:00:00
abstract：:Spin traps are increasingly employed in the detection of free radicals in biological systems, including liver microsomes and isolated hepatocytes. Two spin traps phenyl-t-butyl nitrone (PBN) and 4-pyridyl-l-oxide-t-butyl nitrone (4-POBN) have been tested for their effects on hepatocyte viability and mixed-function oxi...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(86)90010-9
更新日期：1986-11-15 00:00:00
abstract：:Squalene synthase (SQS) catalyses a step following the final branch in the pathway of cholesterol biosynthesis. Inhibition of this enzyme, therefore, is an approach for the treatment of atherosclerosis with the potential for low side effects. We have characterised the inhibition of rat liver microsomal SQS by 3-(biphe...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(96)00090-1
更新日期：1996-06-14 00:00:00
abstract：:The orphan nuclear receptor estrogen-related receptor alpha (ERRalpha) has been implicated in the development of various human malignancies, including breast, prostate, ovary, and colon cancer. ERRalpha, bound to a co-activator protein (e.g., peroxisome proliferator receptor gamma co-activator-1alpha, PGC-1alpha), reg...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2010.05.024
更新日期：2010-09-15 00:00:00
abstract：:Multidrug resistance-associated protein 2 (Mrp2) is an ATP-dependent export pump that mediates the formation of bile-salt-independent bile flow. Disruption of the canalicular localization of Mrp2, without changes in its expression, is observed in chronic liver failure and is accompanied by oxidative stress. We reporte...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2010.09.016
更新日期：2011-01-01 00:00:00
abstract：:Studies were performed to characterise the phospholipase A2 (PLA2) responsible for the greatly increased capacity to release arachidonic acid (AA) of dimethyl sulphoxide (DMSO) differentiated U937 monocytic cells compared to undifferentiated cells (18-fold increase in response to Ca2+ ionophore A23187). Cytosolic PLA2...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(95)02084-5
更新日期：1995-11-27 00:00:00
abstract：:Intact, biological active insulin and pancreatic RNase can be absorbed from the intestinal lumen into the blood circulation. The absorption is dependent on the addition of bile acid (sodium cholate) and proteinase inhibitor. The quantitative absorption of insulin and pancreatic RNase has been demonstrated in an in sit...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(87)90411-4
更新日期：1987-04-01 00:00:00
abstract：:The aim of this review is to summarize current available information about the role of PI3K/AKT/mTOR signaling in head and neck cancer as a potential target for new therapy options. 90% of all head and neck cancers are squamous cell carcinomas (HNSCC). The most common genetic alteration is inactivation of p16 gene whi...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2019.113729
更新日期：2020-02-01 00:00:00
abstract：:The β2-adrenergic receptor (β2AR) is the prototypical member of the heptahelical G protein-coupled receptor (GPCR) superfamily and is well-known to elicit biological effects through both G protein-dependent and G protein-independent signaling cascades. Agonism of β2AR has been described to promote phosphorylation and ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2012.06.012
更新日期：2012-09-01 00:00:00
abstract：:Activation of the P2Y(1) nucleotide receptor in platelets by ADP causes changes in shape and aggregation, mediated by activation of phospholipase C (PLC). Recently, MRS2500(2-iodo-N(6)-methyl-(N)-methanocarba-2'-deoxyadenosine-3',5'-bisphosphate) was introduced as a highly potent and selective antagonist for this rece...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2004.06.026
更新日期：2004-11-15 00:00:00
abstract：:The binding of phenylbutazone (PB) to human serum albumin (HSA) at different pH and in the presence of different NaSCN and urea concentrations that alter the conformation of the protein was examined qualitatively on the basis of extrinsic elliptical strength at 288 nm by means of circular dichroism (CD). The values of...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(92)90595-a
更新日期：1992-03-03 00:00:00
abstract：:The disturbances of the cholesterol synthesis and metabolism described in Alzheimer's disease (AD) may be both a consequence of the neurodegenerative process and a contributor to the pathogenesis. These putative relationships and their underlying mechanisms are not well understood. The aim of this study was to evaluat...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2012.12.007
更新日期：2013-07-01 00:00:00
abstract：:Metastatic migration of murine L1210 leukemia cells, sensitive and resistant to the antitumor agent L-phenylalanine mustard, from the peritoneal cavity of mice to the liver resulted in a 2-fold elevation in their GSH content. This increase in GSH was accompanied by a corresponding increase in their resistance to the d...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(86)90326-6
更新日期：1986-05-15 00:00:00
abstract：:The effect of 3'-deoxythymidin-2'-ene (d4T) on the metabolism of exogenously supplied radiolabeled nucleosides was investigated. Following a 24-hr exposure to 250 microM d4T, we observed no significant effect on the incorporation of [3H]thymidine or [3H]deoxycytidine into DNA. In contrast, the amounts of [3H]uridine, ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(90)90516-n
更新日期：1990-05-15 00:00:00
abstract：:MRS 1754 [N-(4-cyanophenyl)-2-[4-(2,3,6,7-tetrahydro-2,6-dioxo-1,3-dipropyl-1H-purin-8-yl)-phenoxy]acetamide] is a selective antagonist ligand of A(2B) adenosine receptors. This is the least well-defined adenosine receptor subtype, and A(2B) antagonists have potential as antiasthmatic drugs. For use as a radioligand, ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(01)00531-7
更新日期：2001-03-15 00:00:00
abstract：:The challenges associated with developing more effective treatments for neurologic and psychiatric illness such as Alzheimer's disease and schizophrenia are considerable. Both the symptoms and the pathophysiology of these conditions are complex and poorly understood and the clinical presentations across different pati...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2015.07.027
更新日期：2015-10-15 00:00:00
abstract：:Quantitative RNase protection assays were performed to determine the levels of muscarinic receptor subtype (m1-m5) mRNAs in rat hippocampi. Results showed that the m1, m3, and m4 subtype mRNAs were expressed at relatively high levels, but the levels of the m2 and m5 subtype were very low. Three weeks following aspirat...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(97)00074-9
更新日期：1997-05-09 00:00:00
abstract：:Bufuralol hydroxylation activities of liver microsomal cytochrome P450 (P450) enzymes were studied in the rat; the reaction has been used widely in determining levels of liver microsomal P450 2D6, which shows debrisoquine-type genetic polymorphism in humans. Liver microsomes catalyzed the conversion of bufuralol to 1'...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(94)90069-8
更新日期：1994-06-01 00:00:00
abstract：:Human butyrylcholinesterase (E.C. 3.1.1.8) purified from blood plasma has previously been shown to provide protection against up to five and a half times the median lethal dose of an organophosphorus nerve agent in several animal models. In this study the stoichiometric nature of the protection afforded by human butyr...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2019.113670
更新日期：2020-01-01 00:00:00
abstract：:The effect of specifically derivatized dextrans, with or without antiproliferative activity on smooth muscle cells (SMC), was investigated on type I and type III collagen biosynthesis and mRNA levels in post-confluent SMC cultures. Our results indicate that dextran derivatives decreased total protein and collagen synt...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(94)00455-u
更新日期：1995-03-15 00:00:00
abstract：:Escape from the proper control of the cell cycle by up-regulation of cyclins or aberrant activation of cyclin-dependent kinases (CDKs) as well as by inactivation of cellular inhibitors of CDKs (CKI) leads to malignant transformation. Loss of cellular CKIs in cancers provided a rationale for development of pharmacologi...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2008.07.040
更新日期：2008-12-01 00:00:00
abstract：:Blocking spermidine and spermine synthesis in Plasmodium falciparum-infected erythrocytes with irreversible inhibitors of S-adenosylmethionine decarboxylase (AdoMet DC; EC 4.1.1.50), prevented the growth of the parasite in vitro. The most potent of these compounds, MDL 73811, inhibited growth of chloroquine-sensitive ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(91)90174-4
更新日期：1991-06-01 00:00:00
abstract：:The formation, retention and biological activity of the polyglutamate metabolites of the thymidylate synthase (TS) inhibitor N10-propargyl-5,8-dideazafolic acid (CB3717) has been investigated in L1210 murine leukaemia cells grown in vitro. CB3717 polyglutamates were measured by HPLC using high specific activity 3H-CB3...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(88)90094-9
更新日期：1988-11-01 00:00:00
