The action of a drug in promoting or enhancing the effectiveness of another drug.
Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses).
A complex of closely related aminoglycosides obtained from MICROMONOSPORA purpurea and related species. They are broad-spectrum antibiotics, but may cause ear and kidney damage. They act to inhibit PROTEIN BIOSYNTHESIS.
Substances that reduce the growth or reproduction of BACTERIA.
The relationship between the dose of an administered drug and the response of the organism to the drug.
Phenomena and pharmaceutics of compounds that inhibit the function of agonists (DRUG AGONISM) and inverse agonists (DRUG INVERSE AGONISM) for a specific receptor. On their own, antagonists produce no effect by themselves to a receptor, and are said to have neither intrinsic activity nor efficacy.
Glycosylated compounds in which there is an amino substituent on the glycoside. Some of them are clinically important ANTIBIOTICS.
An endocellulase with specificity for the hydrolysis of 1,4-beta-glucosidic linkages in CELLULOSE, lichenin, and cereal beta-glucans.
A drug used in the treatment of angina pectoris, heart failure, conduction defects, and myocardial infarction. It is a partial agonist at beta adrenergic receptors and acts as a coronary vasodilator and cardiotonic agent.
Single preparations containing two or more active agents, for the purpose of their concurrent administration as a fixed dose mixture.
An exocellulase with specificity for the hydrolysis of 1,4-beta-D-glucosidic linkages in CELLULOSE and cellotetraose. It catalyzes the hydrolysis of terminal non-reducing ends of beta-D-glucosides with release of CELLOBIOSE.
Established cell cultures that have the potential to propagate indefinitely.
A mitosporic fungal genus frequently found in soil and on wood. It is sometimes used for controlling pathogenic fungi. Its teleomorph is HYPOCREA.
The action of a drug that may affect the activity, metabolism, or toxicity of another drug.
Therapy with two or more separate preparations given for a combined effect.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.
An antibiotic produced by the soil actinomycete Streptomyces griseus. It acts by inhibiting the initiation and elongation processes during protein synthesis.
Antibiotic complex produced by Streptomyces kanamyceticus from Japanese soil. Comprises 3 components: kanamycin A, the major component, and kanamycins B and C, the minor components.
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
A species of gram-positive, coccoid bacteria commonly isolated from clinical specimens and the human intestinal tract. Most strains are nonhemolytic.
An aminoglycoside, broad-spectrum antibiotic produced by Streptomyces tenebrarius. It is effective against gram-negative bacteria, especially the PSEUDOMONAS species. It is a 10% component of the antibiotic complex, NEBRAMYCIN, produced by the same species.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
A polysaccharide with glucose units linked as in CELLOBIOSE. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
An antiviral derivative of THYMIDINE used mainly in the treatment of primary keratoconjunctivitis and recurrent epithelial keratitis due to HERPES SIMPLEX virus. (From Martindale, The Extra Pharmacopoeia, 30th ed, p557)
A group of antibiotics that contain 6-aminopenicillanic acid with a side chain attached to the 6-amino group. The penicillin nucleus is the chief structural requirement for biological activity. The side-chain structure determines many of the antibacterial and pharmacological characteristics. (Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed, p1065)
A group of peptides characterized by length of 1-2 dozen residues with a high proportion of them being non-proteinogenic, notably alpha-aminoisobutyric acid (Aib) and isovaline, and have a C-terminal amino alcohol and N terminal alkyl group. They are found in FUNGI and some are ANTI-INFECTIVE AGENTS. They form channels or pores in target organisms. The term is a contraction of peptide-Aib-alcohol.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
A cell line derived from cultured tumor cells.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
Proteins prepared by recombinant DNA technology.
Broad-spectrum semisynthetic penicillin derivative used parenterally. It is susceptible to gastric juice and penicillinase and may damage platelet function.
The rate dynamics in chemical or physical systems.
Nonsusceptibility of an organism to the action of penicillins.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Semi-synthetic derivative of penicillin that functions as an orally active broad-spectrum antibiotic.
An organothiophosphorus insecticide that has been used to control pig mange.
A resinous substance obtained from beehives that is used traditionally as an antimicrobial. It is a heterogeneous mixture of many substances.
An organothiophosphorus cholinesterase inhibitor that is used as a systemic and contact insecticide.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
The use of two or more chemicals simultaneously or sequentially in the drug therapy of neoplasms. The drugs need not be in the same dosage form.
The dose amount of poisonous or toxic substance or dose of ionizing radiation required to kill 50% of the tested population.
Substances that destroy fungi by suppressing their ability to grow or reproduce. They differ from FUNGICIDES, INDUSTRIAL because they defend against fungi present in human or animal tissues.
Basic lipopeptide antibiotic group obtained from Bacillus polymyxa. They affect the cell membrane by detergent action and may cause neuromuscular and kidney damage. At least eleven different members of the polymyxin group have been identified, each designated by a letter.
A bacteriostatic antibacterial agent that interferes with folic acid synthesis in susceptible bacteria. Its broad spectrum of activity has been limited by the development of resistance. (From Martindale, The Extra Pharmacopoeia, 30th ed, p208)
Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
A group of anaerobic, rod-shaped bacteria that show up as pink (negative) when treated by the Gram-staining method.
Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.
An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle.
Elements of limited time intervals, contributing to particular results or situations.
An antibiotic produced by Streptomyces fradiae.
One of the three domains of life (the others being Eukarya and ARCHAEA), also called Eubacteria. They are unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. Bacteria can be classified by their response to OXYGEN: aerobic, anaerobic, or facultatively anaerobic; by the mode by which they obtain their energy: chemotrophy (via chemical reaction) or PHOTOTROPHY (via light reaction); for chemotrophs by their source of chemical energy: CHEMOLITHOTROPHY (from inorganic compounds) or chemoorganotrophy (from organic compounds); and by their source for CARBON; NITROGEN; etc.; HETEROTROPHY (from organic sources) or AUTOTROPHY (from CARBON DIOXIDE). They can also be classified by whether or not they stain (based on the structure of their CELL WALLS) with CRYSTAL VIOLET dye: gram-negative or gram-positive.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
Triazole antifungal agent that is used to treat oropharyngeal CANDIDIASIS and cryptococcal MENINGITIS in AIDS.
A semisynthetic ampicillin-derived acylureido penicillin.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
A species of gram-positive bacteria which may be pathogenic for certain insects. It is used for the biological control of the Gypsy moth.

Toxicological findings in a fatal ingestion of methamphetamine. (1/11876)

This paper presents the case history of a fatality caused by the complications brought about by the presence of methamphetamine and ethanol. Drug concentrations are reported from samples obtained approximately 15 min after the subject was last observed to be chewing what was then believed to be gum, 3 h after the initial toxic symptoms were displayed, 6, 11, and 22 h later. The subjects conditions deteriorated over the course of this time, and he was declared dead 33 h after the initial display of toxic symptoms. The toxicological findings and concentration levels of the reported biological specimens concurred with the expected findings in a case of methamphetamine toxicity.  (+info)

Expression of both P1 and P2 purine receptor genes by human articular chondrocytes and profile of ligand-mediated prostaglandin E2 release. (2/11876)

OBJECTIVE: To assess the expression and function of purine receptors in articular chondrocytes. METHODS: Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to screen human chondrocyte RNA for expression of P1 and P2 purine receptor subtypes. Purine-stimulated prostaglandin E2 (PGE2) release from chondrocytes, untreated or treated with recombinant human interleukin-1alpha (rHuIL-1alpha), was assessed by radioimmunoassay. RESULTS: RT-PCR demonstrated that human articular chondrocytes transcribe messenger RNA for the P1 receptor subtypes A2a and A2b and the P2 receptor subtype P2Y2, but not for the P1 receptor subtypes A1 and A3. The P1 receptor agonists adenosine and 5'-N-ethylcarboxamidoadenosine did not change PGE2 release from chondrocytes. The P2Y2 agonists ATP and UTP stimulated a small release of PGE2 that was potentiated after pretreatment with rHuIL-1alpha. PGE2 release in response to ATP and UTP cotreatment was not additive, but release in response to coaddition of ATP and bradykinin (BK) or UTP and BK was additive, consistent with ATP and UTP competition for the same receptor site. The potentiation of PGE2 release in response to ATP and UTP after rHuIL-1alpha pretreatment was mimicked by phorbol myristate acetate. CONCLUSION: Human chondrocytes express both P1 and P2 purine receptor subtypes. The function of the P1 receptor subtype is not yet known, but stimulation of the P2Y2 receptor increases IL-1-mediated PGE2 release.  (+info)

Estrogen enhancement of anti-double-stranded DNA antibody and immunoglobulin G production in peripheral blood mononuclear cells from patients with systemic lupus erythematosus. (3/11876)

OBJECTIVE: To study the in vitro effect of estrogen on IgG anti-double-stranded DNA (anti-dsDNA) antibody and total IgG production in peripheral blood mononuclear cells (PBMC) from patients with systemic lupus erythematosus (SLE), in order to elucidate its regulatory role in SLE. METHODS: PBMC from SLE patients and normal donors were cultured with 17beta-estradiol (E2). IgG anti-dsDNA antibodies, total IgG, and cytokine activity in the culture supernatants were measured by enzyme-linked immunosorbent assay. RESULTS: E2 enhanced production of IgG anti-dsDNA antibodies as well as total IgG in PBMC from SLE patients. Anti-dsDNA production in patients with inactive disease was less responsive to E2 than that in patients with active disease. E2 also enhanced total IgG, but not anti-dsDNA, production in the PBMC of normal donors. Antibody production was increased by E2 to a lesser extent in patients' B cells than in their PBMC. Anti-interleukin-10 (anti-IL-10) antibodies partially blocked the E2-induced increase in antibody production in patients' PBMC, but anti-IL-10 had no effect on B cells. E2 increased IL-10 production by patients' monocytes. Exogenous IL-10 acted additively with E2 in increasing antibody production in patients' B cells. CONCLUSION: These results suggest that E2 may polyclonally increase the production of IgG, including IgG anti-dsDNA, in SLE patients' PBMC by enhancing B cell activity and by promoting IL-10 production in monocytes. These findings support the involvement of E2 in the pathogenesis of SLE.  (+info)

Synergistic protective effects of antioxidant and nitric oxide synthase inhibitor in transient focal ischemia. (4/11876)

Both nitric oxide synthase (NOS) inhibitors and free radical scavengers have been shown to protect brain tissue in ischemia-reperfusion injury. Nitric oxide and superoxide anion act via distinct mechanisms and react together to form the highly deleterious peroxynitrite. Therefore the authors examined the effects and the interaction between the NOS inhibitor, NG nitro-L-arginine (LNA) and the antioxidant/superoxide scavenger, di-tert-butyl-hydroxybenzoic acid (DtBHB) in the rat submitted to 2 hours of middle cerebral artery occlusion. Posttreatment was initiated 4 hours after the onset of ischemia and infarct volume was measured at 48 hours. The dose-related effect of LNA resulted in a bell-shaped curve: 15, 56, 65, and 33% reduction of total infarct for 0.03, 0.1, 0.3, and 1 mg/kg (intravenously [IV]) respectively and 11% increase in infarct volume for 3 mg/kg (IV). Whereas DtBHB (20 mg/kg; intraperitoneally [IP]) was ineffective, the dose of 60 mg/kg produced 65% protection in infarct volume. The combination of a subthreshold dose of LNA (0.03 mg/kg; IV) and DtBHB (20 mg/kg; IP) resulted in significant reduction (49%) in infarct volume. These results show that LNA and DtBHB act synergistically to provide a consistent neuroprotection against ischemic injury when administered 4 hours after ischemia. This suggests that nitric oxide and free radicals are involved and interact in synergy in ischemia-reperfusion injury.  (+info)

Spinal antinociceptive synergism between morphine and clonidine persists in mice made acutely or chronically tolerant to morphine. (5/11876)

Morphine (Mor) tolerance has been attributed to a reduction of opioid-adrenergic antinociceptive synergy at the spinal level. The present experiments tested the interaction of intrathecally (i.t.) administered Mor-clonidine (Clon) combinations in mice made acutely or chronically tolerant to Mor. ICR mice were pretreated with Mor either acutely (40 nmol i.t., 8 h; 100 mg/kg s.c., 4 h) or chronically (3 mg/kg s.c. every 6 h days 1 and 2; 5 mg/kg s.c. every 6 h days 3 and 4). Antinociception was detected via the hot water (52.5 degrees C) tail-flick test. After the tail-flick latencies returned to baseline levels, dose-response curves were generated to Mor, Clon, and Mor-Clon combinations in tolerant and control mice. Development of tolerance was confirmed by significant rightward shifts of the Mor dose-response curves in tolerant mice compared with controls. Isobolographic analysis was conducted; the experimental combined ED50 values were compared statistically against their respective theoretical additive ED50 values. In all Mor-pretreated groups, the combination of Mor and Clon resulted in significant leftward shifts in the dose-response curves compared with those of each agonist administered separately. In all tolerant and control groups, the combination of Mor and Clon produced an ED50 value significantly less than the corresponding theoretical additive ED50 value. Mor and Clon synergized in Mor-tolerant as well as in control mice. Spinally administered adrenergic/opioid synergistic combinations may be effective therapeutic strategies to manage pain in patients apparently tolerant to the analgesic effects of Mor.  (+info)

Angiotensin receptor subtype 1 mediates angiotensin II enhancement of isoproterenol-induced cyclic AMP production in preglomerular microvascular smooth muscle cells. (6/11876)

In a previous study, we found that angiotensin (Ang) II enhances beta-adrenoceptor-induced cAMP production in cultured preglomerular microvascular smooth muscle cells (PMVSMCs) obtained from spontaneously hypertensive rats. The purpose of the present investigation was to identify the Ang receptor subtypes that mediate this effect. In our first study, we compared the ability of Ang II, Ang III, Ang (3-8), and Ang (1-7) to increase cAMP production in isoproterenol (1 microM)-treated PMVSMCs. Each peptide was tested at 0.1, 1, 10, 100, and 1000 nM. Both Ang II and Ang III increased intracellular (EC50s, 1 and 11 nM, respectively) and extracellular (EC50s, 2 and 14 nM, respectively) cAMP levels in a concentration-dependent fashion. In contrast, Ang (3-8) and Ang (1-7) did not enhance either intracellular or extracellular cAMP levels at any concentration tested. In our second study, we examined the ability of L 158809 [a selective Ang receptor subtype 1 (AT1) receptor antagonist] to inhibit Ang II (100 nM) and Ang III (100 nM) enhancement of isoproterenol (1 microM)-induced cAMP production in PMVSMCs. L 158809 (10 nM) abolished or nearly abolished (p <.001) Ang II and Ang III enhancement of isoproterenol-induced intracellular and extracellular cAMP levels. In contrast, PD 123319 (300 nM; a selective AT2 receptor antagonist) did not significantly alter Ang II enhancement of isoproterenol-induced intracellular or extracellular cAMP levels. We conclude that AT1 receptors, but not AT2, Ang (3-8), nor Ang (1-7) receptors mediate Ang II and Ang III enhancement of beta-adrenoceptor-induced cAMP production in cultured PMVSMCs.  (+info)

1,25-Dihydroxyvitamin D3 enhances the susceptibility of breast cancer cells to doxorubicin-induced oxidative damage. (7/11876)

1,25-Dihydroxyvitamin D3 (1,25(OH)2D3), the hormonal form of vitamin D, has anticancer activity in vivo and in vitro. Doxorubicin exerts its cytotoxic effect on tumor cells mainly by two mechanisms: (a) generation of reactive oxygen species (ROS); and (b) inhibition of topoisomerase II. We studied the combined cytotoxic action of 1,25(OH)2D3 and doxorubicin on MCF-7 breast cancer cells. Pretreatement with 1,25(OH)2D3 resulted in enhanced cytotoxicity of doxorubicin. The average enhancing effect after a 72-h pretreatment with 1,25(OH)2D3 (10 nM) followed by a 24-h treatment with 1 microg/ml doxorubicin was 74+/-9% (mean +/- SE). Under these experimental conditions, 1,25(OH)2D3 on its own did not affect cell number or viability. 1,25(OH)2D3 also enhanced the cytotoxic activity of another ROS generating quinone, menadione, but did not affect cytotoxicity induced by the topoisomerase inhibitor etoposide. The antioxidant N-acetylcysteine slightly reduced the cytotoxic activity of doxorubicin but had a marked protective effect against the combined action of 1,25(OH)2D3 and doxorubicin. These results indicate that ROS are involved in the interaction between 1,25(OH)2D3 and doxorubicin. 1,25(OH)2D3 also increased doxorubicin cytotoxicity in primary cultures of rat cardiomyocytes. Treatment of MCF-7 cells with 1,25(OH)2D3 alone markedly reduced the activity, protein, and mRNA levels of the cytoplasmic antioxidant enzyme Cu/Zn superoxide dismutase, which indicated that the hormone inhibits its biosynthesis. This reduction in the antioxidant capacity of the cells could account for the synergistic interaction between 1,25(OH)2D3 and doxorubicin and may also suggest increased efficacy of 1,25(OH)2D3 or its analogues in combination with other ROS-generating anticancer therapeutic modalities.  (+info)

SDZ PSC 833, the cyclosporine A analogue and multidrug resistance modulator, activates ceramide synthesis and increases vinblastine sensitivity in drug-sensitive and drug-resistant cancer cells. (8/11876)

Resistance to chemotherapy is the major cause of cancer treatment failure. Insight into the mechanism of action of agents that modulate multidrug resistance (MDR) is instrumental for the design of more effective treatment modalities. Here we show, using KB-V-1 MDR human epidermoid carcinoma cells and [3H]palmitic acid as metabolic tracer, that the MDR modulator SDZ PSC 833 (PSC 833) activates ceramide synthesis. In a short time course experiment, ceramide was generated as early as 15 min (40% increase) after the addition of PSC 833 (5.0 microM), and by 3 h, [3H]ceramide was >3-fold that of control cells. A 24-h dose-response experiment showed that at 1.0 and 10 microM PSC 833, ceramide levels were 2.5- and 13.6-fold higher, respectively, than in untreated cells. Concomitant with the increase in cellular ceramide was a progressive decrease in cell survival, suggesting that ceramide elicited a cytotoxic response. Analysis of DNA in cells treated with PSC 833 showed oligonucleosomal DNA fragmentation, characteristic of apoptosis. The inclusion of fumonisin B1, a ceramide synthase inhibitor, blocked PSC 833-induced ceramide generation. Assessment of ceramide mass by TLC lipid charring confirmed that PSC 833 markedly enhanced ceramide synthesis, not only in KB-V-1 cells but also in wild-type KB-3-1 cells. The capacity of PSC 833 to reverse drug resistance was demonstrated with vinblastine. Whereas each agent at a concentration of 1.0 microM reduced cell survival by approximately 20%, when PSC 833 and vinblastine were coadministered, cell viability fell to zero. In parallel experiments measuring ceramide metabolism, it was shown that the PSC 833/vinblastine combination synergistically increased cellular ceramide levels. Vinblastine toxicity, also intensified by PSC 833 in wild-type KB-3-1 cells, was as well accompanied by enhanced ceramide formation. These data demonstrate that PSC 833 has mechanisms of action in addition to P-glycoprotein chemotherapy efflux pumping.  (+info)

We have investigated the effects of interferon-α (IFN-α) and 5-fluorouracil (5-FU) on meningioma cells in two different culture systems, evaluated by the uptake of radiolabelled methionine. With both IFN-α and 5-FU an inhibitory effect on the uptake of radiolabelled methionine by the meningioma cells was demonstrated, and we found a synergistic inhibitory effect with a combination of IFN-α and 5-FU. To obtain a maximal inhibition of cell metabolism without causing cell toxicity, we were able to decrease the dose of 5-FU by simultaneously adding IFN-α. Our results suggest that a combined treatment of IFN-α and 5-FU may be a successful alternative for patients with inoperable meningiomas. A novel in vitro positron emission tomography technique was used for the study of metabolic changes in tumour cells caused by drug treatment, which is complementary to conventional cell culture techniques.. ...
In this study, we systematically explored drug combinations to evaluate specific and promiscuous models of drug synergy. We developed a sensitive drug interaction classification assay and used it to find 38 synergistic drug pairs, of which only 1 (Terbinafine-Rapamycin) had been previously reported (Lehar et al, 2007).. To identify cases of specific synergy, predicted by synergistic genetic interaction, we integrated a newly assembled catalog of drug targets with the synergistic genetic interaction network. Although we tested 38 drug pairs corresponding to genetic interactions and found 14 (37%) to be synergistic, it is difficult to assess whether these drug synergies are better explained by genetic interaction or promiscuous synergy. Indeed, after accounting for background rates of synergy for each drug, our results did not show a significant enrichment for drug synergy among drugs targeting the products of genetically interacting genes.. There are many potential explanations for this ...
TY - JOUR. T1 - Divergent synergic effects in carcinogenesis initiation by simultaneous exposure to two genotoxic carcinogens. AU - Verdina, A.. AU - Zito, R.. AU - Federico, A.. AU - Falasca, G.. AU - Galati, R.. PY - 2000. Y1 - 2000. N2 - Carcinogenesis is a complex and multistep process starting from initiation to tumor progression. Synergistic mechanisms can occur at every step of the process. The aim of this work was to provide information about the effect of chemical carcinogens which, if administered in combination, result in positive as well as negative synergistic effects. In order to evaluate whether for some carcinogens synergism occurs at the initiation step, we compared the effects of Ethylmethanesulfonate (EMS) on Benzo[a]pyrene (BP)-DNA adducts formation in the liver and lung of male Swiss mice treated for seven days by i.p. dose of EMS (1.2 mg/Kg b.w.) alone or by simultaneous administration of three doses of BP (25, 50, 100 mg/Kg b.w.) injected i.p. or the first day of ...
TY - JOUR. T1 - Dual-mode nanoparticle probes for high-performance magnetic resonance and fluorescence imaging of neuroblastoma. AU - Lee, Jae Hyun. AU - Jun, Young Wook. AU - Yeon, Soo In. AU - Shin, Jeon Soo. AU - Cheon, Jinwoo. PY - 2006/12/11. Y1 - 2006/12/11. N2 - Working together: A core-satellite hybrid nanoparticle probe provides highly improved fluorescence and magnetic resonance (MR) imaging capabilities through synergistic enhancement of its respective components. These hybrid nanoprobes can be used for dual-modal fluorescence and MR imaging of neuroblastoma with expressed polysialic acids.. AB - Working together: A core-satellite hybrid nanoparticle probe provides highly improved fluorescence and magnetic resonance (MR) imaging capabilities through synergistic enhancement of its respective components. These hybrid nanoprobes can be used for dual-modal fluorescence and MR imaging of neuroblastoma with expressed polysialic acids.. UR - ...
Clinically relevant epithelial lining fluid concentrations of meropenem with ciprofloxacin provide synergistic killing and resistance suppression of hypermutable Pseudomonas aeruginosa in a dynamic biofilm model. Antimicrob Agents Chemother. 2020 May 04;: Authors: Bilal H, Bergen PJ, Tait JR, Wallis SC, Peleg AY, Roberts JA, Oliver A, Nation RL, Landersdorfer CB Abstract Trea...
The results showed: i) that both PC3 and LNCaP are sensitive to single and combination treatments regardless of hormone sensitivity status, ii) that treatment induced dual death pathways (apoptosis and necrosis) in both cell types, iii) that growth inhibition in both cell types correlated positively with cell death via apoptosis at lower drug concentrations and necrosis at higher concentrations, iv) that combination of genistein and beta-lapachone had synergistic inhibitory effects on growth and proliferation in both cell types ...
Aberrant growth factor production is a prevalent mechanism in tumourigenesis. If T-cells responded positively to a cancer-derived cytokine, this might result in selective enhancement of function within the tumour microenvironment. Here, we have chosen colony-stimulating factor-1 (CSF-1) as a candidate to test this concept. CSF-1 is greatly overproduced in many cancers but has no direct effects upon T-lymphocytes, which do not express the c-fms-encoded CSF-1 receptor. To confer CSF-1-responsiveness, we have expressed the human c fins gene in immortalized and primary T-cells. Addition of soluble CSF-1 resulted in synergistic enhancement of IL-2-driven T-cell proliferation. CSF-1 also co-stimulated the production of interferon (IFN)-gamma by activated T-cells. These effects required Y809 of the CSF-1R and activation of the Ras-MEK-MAP kinase cascade, but were independent of PI3K signalling. T-cells that express c-fins are also responsive to membrane-anchored CSF-1 (mCSF-1) which, unlike its soluble ...
Melinamide in combination with either retinol or retinyl ester resulted in a synergistic enhancement in keratinocyte proliferation. The effects of the retinol or retinyl esters in combination with fatty acid amides were analogous to treatment with retinoic acid.
All three drugs are antibodies that block a receptor on the surface of cells called the epidermal growth factor receptor, or EGFR. This receptor plays a role in the formation and spread of cancerous tumors. Used in combination with chemotherapy or radiation, blocking EGFR may prevent cancer from growing. Prof. Sela and colleagues - Dr. Esther Aboud-Pirak and Dr. Esther Hurwitz - discovered, a number of years ago, that EGFR-inhibiting antibodies produce a synergistic anticancer effect when used together with chemotherapy ...
Fig. 7. Comparison of the effect of RAD51 antisense molecule and RAD51 inhibitor IBR2 on the cytotoxicity of olaparib and other anticancer drugs. (A, C, and D) Cells were cultured in 25-cm2 flasks, and exposed to siRNA as described in Materials and Methods for 4 hours, followed by addition of one volume of medium. After a further 20 hours, the medium was changed and the drug indicated was added to the final desired concentration. The proliferation of cells in the presence of the indicated concentration of siRNA, as a percentage of the scrambled siRNA control, in (A) was 85.3% ± 11.0% (n = 9) for A549b and 70.2% ± 11.9% (7) for HT-29. In (C and D) the proliferation was 51.8% ± 12.7% (8) for A549b and 62.4% ± 11.6% (9) for DU145. (B) A549b cells were grown in 96-well plates and treated with simultaneous exposure to IBR2 and olaparib at the concentrations indicated. The relative cell density was determined after 4 days by viability staining. The relative density of cells treated with both ...
High expression levels of Inhibitors of Apoptosis Proteins (IAPs) have been correlated with poor cancer prognosis and block the cell death pathway by interfering with caspase activation. SMAC-mimetics are small-molecule inhibitors of IAPs that mimic the endogenous SMAC and promote the induction of cell death by neutralizing IAPs. In this study, anti-tumour activity of new SMAC-mimetics Birinapant and AT-406 is evaluated against colorectal adenocarcinoma cells and IAP cross-talk with either oncogenic BRAF or BCL-2, or with the TRAIL are further exploited towards rational combined protocols. It is shown that pre-treatment of SMAC-mimetics followed by their combined treatment with BRAF inhibitors can decrease cell viability, migration and can very efficiently sensitize colorectal tumour cells to apoptosis. Moreover, co-treatment of TRAIL with SMAC-mimetics can efficiently sensitize resistant tumour cells to apoptosis synergistically, as shown by median effect analysis. Finally, Birinapant and AT-406 can
In Response: Ropero et al. (1) conducted an evaluation of the combination of Herceptin and tamoxifen with analyses of drug interaction, the conclusions of which partially contradict our findings previously reported in this journal (3). Similar to our results, they found the drug combination to give a greater growth-inhibitory effect than either agent alone using breast cancer cells in culture. However, using similar pharmacologic analyses of drug interactions, we found the combination to give synergistic growth inhibition, whereas Ropero et al. found the combination to have an antagonistic interaction at doses corresponding to the IC30. Both studies used estrogen receptor-positive, HER2-overexpressing BT-474 human breast carcinoma cells, and it seems that biological differences in the cells used, as well as differences in some of the experimental details, likely account for the disparate outcomes of drug interaction analysis.. Vázquez-Martín et al. comment on our modeling of drug interactions. ...
Combination with other small molecule drugs represents a promising strategy to improve therapeutic efficacy of FLT3 inhibitors in the clinic. We demonstrated that combining ABT-869, a FLT3 inhibitor, with SAHA, a HDAC inhibitor, led to synergistic killing of the AML cells with FLT3 mutations and suppression of colony formation. We identified a core gene signature that is uniquely induced by the combination treatment in 2 different leukemia cell lines. Among these, we showed that downregulation of PTP4A3 (PRL-3) played a role in this synergism. PRL-3 is downstream of FLT3 signaling and ectopic expression of PRL-3 conferred therapeutic resistance through upregulation of STAT (signal transducers and activators of transcription) pathway activity and anti-apoptotic Mcl-1 protein. PRL-3 interacts with HDAC4 and SAHA downregulates PRL-3 via a proteasome dependent pathway. In addition, PRL-3 protein was identified in 47% of AML cases, but was absent in myeloid cells in normal bone marrows. Our results ...
Historically, understanding of acquired resistance (AQR) to combination treatment has been based on knowledge of resistance to its component agents. To test whether an altered drug interaction could be an additional factor in AQR to combination treatment, models of AQR to combination and single agent MEK and PI3K inhibitor treatment were generated. Combination indices indicated combination treatment of PI3K and MEK inhibitors remained synergistic in cells with AQR to single agent but not combination AQR cells. Differences were also observed between the models in cellular phenotypes, pathway signaling and drug cross-resistance. Genomics implicated TGFB2-EDN1 overexpression as candidate determinants in models of AQR to combination treatment. Supplementation of endothelin in parental cells converted synergism to antagonism. Silencing of TGFB2 or EDN1 in cells with AQR conferred synergy between PI3K and MEK inhibitor. These results highlight that AQR to combination treatment may develop through ...
Novel treatment trend for cancer - Combining radiotherapy and immunotherapy synergistically enhances local and systemic tumor control.
The present invention relates to synergistic combinations of immunostimulatory CpG oligonucleotides and immunopotentiating cytokines. In particular, the invention relates to methods of stimulating an immune response using the synergistic combination of compounds and products related thereto.
does anyone know of any drug combinations that show synergistic effects on mcf-7, or other breat cancer cell lines? thanks!. ...
Scheithauer, W., Temsch, E.M., Jakesz, R. (1987) Preclinical evaluation of synergistic drug combinations of mitoxantrone potentially active against human colorectal and gastric adenocarcinoma. In: Progress in Antimicrobial and Anticancer Chemotherapy. Ecomed Verlag, Landsberg, BRD, pp. 814-816 ...
Small molecule inhibitors of signal transduction pathways can elicit complex and sometimes non-intuitive molecular responses in cancer cells. Increasing evidence supports the notion that these responses are important mediators of de novo drug resistance. We systematically assessed molecular and cellular responses to MEK inhibitors, aiming at identifying meaningful targets for combination therapies. Proteomic analyses revealed an EGFR-dependent feedback loop resulting in activation of the PI3 kinase pathway following MEK inhibition. In agreement with this, combinations of MEK inhibitors and inhibitors of EGFR inhibitors or PI3 kinase show synergistic effects on cell proliferation and apoptosis rates in molecularly defined disease subtypes. To further explore molecular networks affected by MEK inhibition, Bayesian network inference algorithms were applied and reverse-engineered networks were generated that are amenable to in silico forward-simulation. Using this technology, new, MEK-dependent, ...
Today the norm in modern cancer treatment is to use different forms of drug combinations. Recently anti-cancer treatment using drug combinations has gained increased attention due to the outstanding pharmacotherapeutic opportunities provided by combination therapies. However, the potential of this field is largely unexplored, partly due to the complexities associated with the astronomical number of possible combinations and partly due to the lack of means for quantifying clinically relevant adverse side effects in the early stages of the combination discovery and development process. This has resulted in relatively limited progress in this area. Motivated by this unfortunate state-of-affairs, the research reported in this thesis was aimed at developing and implementing computational and experimental methods to facilitate and accelerate the discovery and development of anti-cancer therapies. In paper I, the largely overlooked concept of therapeutic synergy is re-introduced and demonstrated to be ... - Natural Health Resource - The worlds most widely referenced, open access, natural medicine database, with 30,000+ study abstracts and growing daily
These so-called epigenetic therapy drugs, used together, achieved robust anti-tumor responses in human cancer cell lines and mice.
On the Functional Recovery Mechanism of the Cerebral Nervous System in Diabetic State under the Combination Effect of Exercise and Medication
On the Functional Recovery Mechanism of the Cerebral Nervous System in Diabetic State under the Combination Effect of Exercise and Medication
Biocidin® is a synergistic combination of botanical medicines which targets the entire GI tract and supports microbiome balance for healthy digestion and elimination.
need for synergistic combination of drugs for better efficacy and safety profile. Drug repositioning is a term to define the process of finding new endications for existing drugs. Successful clinical evidence of a number of non-cancer drugs for cancer. ...
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Definition of synergism: Interaction between two or more agents, entities, factors, or substances that produces an effect greater than the sum of their individual effects. Also called synergetic effect or synergistic effect, ...
Observe the colonies on your plate, comparing any differences in the appearance of the colony growth of each isolate, alone vs mixed. Look first at each control culture: the inoculum in each of the diagonal spots is a pure culture control as are the spots in the column on the far left. Compare each spot where two isolates are mixed to the control spots where each isolate is growing alone. Is either isolate growing better in combination than alone? If so, you have found a beneficial interaction. For example, in the assay shown above, it appears that 2+4 grows better than either 2 does alone, a positive interaction for isolate 2. Its hard to say what the presence of 2 does for 4 since isolate 2s heavy growth is making it hard to see what 4 is doing when in combo with 2. In contrast, isolates 2+8 appear to be grow equally well in combination as they do separately. We would not assess their relationship as either beneficial or antagonistic. Check carefully for combinations that show an ...
क्या आप जानते हैं Synergy का हिन्दी में क्या मतलब होता है? सिनर्जी क्या होता है जिसे हिंदी में सहक्रिया कहते है। इसके माध्यम से आपको Synergy के बारे में बहुत सारी महत्वपूर्ण जानकारी Synonyms, Antonyms के बारे में हिंदी में जानकारी मिल जाएगी।. पाइए Synergy की जानकारी और हिन्दी में परिभाषा अपनी हिंदी भाषा में बहुत ही आसान शब्दों में पढ़ सकते हैं, को रोजाना पढ़ें, साथ ही हमसे फेसबुक, ट्विटर और इंस्टाग्राम पर ...
I just posted a HyGrid piece. And I checked my old pieces. My last one was 9 years ago.. I didnt think it had been that long ...
Dedifferentiated liposarcoma (DDLS) is a rare but aggressive cancer with high recurrence and low response rates to targeted therapies. Increasing treatment efficacy may require combinations of targeted agents that counteract the effects of multiple abnormalities. To identify a possible multicomponent therapy, we performed a combinatorial drug screen in a DDLS-derived cell line and identified cyclin-dependent kinase 4 (CDK4) and insulin-like growth factor 1 receptor (IGF1R) as synergistic drug targets. We measured the phosphorylation of multiple proteins and cell viability in response to systematic drug combinations and derived computational models of the signaling network. These models predict that the observed synergy in reducing cell viability with CDK4 and IGF1R inhibitors depends on the activity of the AKT pathway. Experiments confirmed that combined inhibition of CDK4 and IGF1R cooperatively suppresses the activation of proteins within the AKT pathway. Consistent with these findings, ...
This study suggests a synergic effect of oral contraceptive use, GSTP1 polymorphisms, and HR-HPV infection in the development of cervical lesions.
2205 HER-2/neu and estrogen receptor (ER) play critical roles in breast cancer. HER-2/neu and ER are validated therapeutic targets; the anti-HER-2/neu antibody Herceptin and the antiestrogen tamoxifen are effective drugs targeting these two receptors. Retinoids have also been shown to inhibit breast cancer growth. We find that all-trans retinoic acid (atRA) downregulates phosphorylation of HER-2/neu and decreases ER activity in BT-474 human breast cancer cells. We thus hypothesize that treatment with atRA and simultaneous targeting of HER-2/neu and/or ER may synergistically inhibit growth of breast cancer cells. We find that combining atRA with Herceptin, tamoxifen, or both results in strong synergistic growth inhibition of BT-474 breast cancer cells. To elucidate the molecular mechanisms underlying this synergistic growth inhibition, we examined the effects of these various drug combinations on cell cycle and apoptosis. We find that atRA, Herceptin, and tamoxifen all lead to an enhanced ...
The synergistic combination of docetaxel (DTX) and cisplatin (CIS) by local drug delivery with a pluronic lecithin organogel (PLO) to facilitate high drug concentrations at tumor sites and less nonspecific distribution to normal organs is thought to be beneficial in chemotherapy. In this study, using Capryol-90 (C90) with the addition of lecithin as the oil phase was developed to carry DTX, which was then incorporated into a PLO-containing CIS to formulate a dual-drug injectable PLO for local delivery. An optimal PLO composite, P13L0.15O1.5, composed of PF127:lecithin:C90 at a 13:0.15:1.5 weight ratio was obtained. The sol-gel transition temperature of P13L0.15O1.5 was found to be 33 °C. Tumor inhibition studies illustrated that DTX/CIS-loaded P13L0.15O1.5 could efficiently suppress tumor growth by both intratumoral and peritumoral injections in SKOV-3 xenograft mouse model. Pharmacokinetic studies showed that subcutaneous administration of P13L0.15O1.5 was able to sustain the release of DTX ...
It has been suggested that combined effect of natural products may improve the treatment effectiveness in combating proliferation of cancer cells. The present study was undertaken to evaluate the possibility that the combination of xanthorrhizol and curcumin might show synergistic growth inhibitory effect towards MDA-MB-231 human breast cancer cells via apoptosis induction. The effective dose that produced 50% growth inhibition (GI50) was calculated from the log dose-response curve of fixed-combinations of xanthorrhizol and curcumin generated from the sulforhodamine B (SRB) assay. The experimental GI50 value was used to determine the synergistic activity of the combination treatment by isobolographic analysis and combination-index method. Further investigation of mode of cell death induced by the combination treatment was conducted in the present study. Isobole analysis revealed that substances interaction was synergistic when xanthorrhizol and curcumin were added concurrently to the cultures but merely
Uses Products. Tokarska, Katarzyna, Łukasz Lamch, Beata Piechota, Kamil Żukowski, Michał Chudy, Kazimiera A. Wilk, and Zbigniew Brzózka. Co-delivery of IR-768 and daunorubicin using mPEG-b-PLGA micelles for synergistic enhancement of combination therapy of melanoma. Journal of Photochemistry and Photobiology B: Biology (2020): 111981 ...
Learning from nature: The development of an MoS2/Ta3N5 nanocomposite as a catalyst for selective aerobic oxidation by O2 activation was inspired by the nitrogenase enzymes in nature. The superior performance of this biomimetic catalyst, which shows potential for the selective oxidation of multifunctional substrates (see picture), results from the integration of Ta3N5 and MoS2 at the nanoscale and the synergistic enhancement of their activity. ...
Ideally, drug interactions are scored from a checkerboard assay relative to the simple null model, indicating that the interaction of a drug with itself is additive (14, 15). Thus, with the Loewe additivity model, if a combinations effect is higher or lower than additivity, the combination is synergistic or antagonistic, respectively (Fig. 1A). We may visualize this intuitive interpretation of the checkerboard by evaluating the contour of a common phenotype (isobole). A straight contour indicates additivity, whereas concave and convex contours are observed in synergistic and antagonistic interactions, respectively (Fig. 1A). The shape of this curve is quantified using the fractional inhibitory concentration (FIC), the standard metric of interaction scores. In the absence of an efficient checkerboard assay, the Bliss multiplicative model has become a commonly used scoring system for determining drug interactions. The Bliss multiplicative model defines the expected phenotype [such as median ...
A high-risk group of patients with follicular lymphoma could benefit from a novel drug combination, according to a new study published in the Journal of Experimental Medicine.
With the emergence of multidrug-resistant organisms, combining medicinal plants with synthetic or orthodox medicines against resistant bacteria becomes necessary. In this study, interactions between methanolic extract of Acacia mearnsii and eight antibiotics were investigated by agar diffusion and checkerboard assays. The minimum inhibitory concentrations (MICs) of all the antibiotics ranged between 0.020 and 500 µg/mL while that of the crude extract varied between 0.156 and 1.25 mg/mL. The agar diffusion assay showed that extract-kanamycin combination had zones of inhibition ≥20 ± 1.0 mm in all the bacteria tested (100%), followed by extract-chloramphenicol (90%) | extract-ciprofloxacin = extract-tetracycline (70%) | extract-amoxicillin (60%) | extract-nalidixic acid (50%) | extract-erythromycin (40%) | extract-metronidazole (20%). The checkerboard showed synergistic interaction (61.25%), additivity/indifference (23.75%) and antagonistic (15%) effects. The synergistic interaction was most expressed
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Results In line with robust T and B cell activation, IFN-γ, IFNα, CXCL13, IgG and IgM production was achieved by a combination of SEB and TLR9 (all at least p,0.001). LEF dose dependently inhibited B and T cell proliferation, Interferon, CXCL13 and immunoglobulin production. HCQ dose dependently inhibited B cell proliferation, IFN-α, CXCL13, and immunoglobulin production. T cell proliferation and IFN-γ production were inhibited by HCQ only at higher concentrations. At several suboptimal concentrations LEF and HCQ additively inhibited T cell proliferation both in healthy individuals and in pSS patients. (Figure 1). Significant additive effects were seen for all outcome measures except IFN-α. Since IFNa was already robustly inhibited by HCQ alone (eg.for pSS 90% at 3.3 μM, p,0.001), only trends towards additive effects were observed. ...
TY - JOUR. T1 - Synergistic inhibition of delayed rectifier K + and voltage-gated Na + currents by artemisinin in pituitary tumor (GH 3 ) cells AU - So, Edmund Cheung. AU - Wu, Sheng Nan. AU - Wu, Ping Ching. AU - Chen, Hui Zhen. AU - Yang, Chia Jung. N1 - Funding Information: This work was supported by National Cheng Kung University (grant numbers D104-35A16) to Dr. Sheng-Nan Wu and Tainan Municipal An Nan Hospital (grant number ANRF - 猃爃瘁猂I to Dr. Edmund Cheunagn dS oM inistry of Science and Technology (grant number 105-2221-E-006 -088) to Dr. Ping-Ching Wu.. PY - 2017/6/1. Y1 - 2017/6/1. N2 - Background: Artemisinin (ART) is an anti-malarial agent reported to influence endocrine function. Methods: Effects of ART on ionic currents and action potentials (APs) in pituitary tumor (GH 3 ) cells were evaluated by patch clamp techniques. Results: ART inhibited the amplitude of delayed-rectifier K + current (I K(DR) ) in response to membrane depolarization and accelerated the process of ...
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5592 Abstract Although a number of methods for assessing drug interactions are available, most methods lack a means of selecting combinations of doses efficiently in planning such experiments. The power-maximized design, derived based on the uniform measures of all possible dose combinations of interest, is able to select the drug combinations (doses of each constituent drug) and to determine the required number of replicates at each combination in order to detect synergy, additivity or antagonism, with pre-specified statistical power for the experiment. An F-test is proposed to detect departures from additivity for combinations of two drugs. To explore the joint effect of the combination, a 3-dimensional combination index surface characterizes the interaction of a two-drug combination estimated using the B-splines. Synergism is manifested as a substantial drop in the combination index which is a 2-dimensional slice of the combination index surface. These methods were applied to evaluate SAHA ...
The scheduled delivery of synergistic drug combinations is increasingly recognized as highly effective against advanced solid tumors. Of particular interest are composite systems that release a sequence of drugs with defined kinetics and molar ratios to enhance therapeutic effect, while minimizing the dose to patie
Oncotarget | Fiorella Vanderhoeven, Analía Lourdes Redondo, Ana Laura Martinez, Laura María Vargas-Roig, Angel Matias Sanchez, Marina Inés Flamini
GPs need to be aware of the bleeding risks associated with the use of chemotherapy or biological therapy alongside cancer drugs that restrict blood vessel growth, a US study suggests.
I have a protein-protein interaction that I have originally detected in bacterial two-hybrid system and pull-down experiments with bacterially expressed proteins also show positive interaction. Now I would like to confirm this interaction also in eukaryotic cells by coimmunoprecipitating the two. Since I do not have antibodies for these proteins, I am using GFP -(Bait) and HA-tagged (target) proteins and thus transfected cells. I have performed the experiment couple of times, and it kind of looks promising: I have positive interaction when the two proteins are present and all negative controls are negative. What makes me doubt is that I do not concentrate the target protein in the immunoprecipitation, that is that my band is weaker in the immunoprecipitation sample than in the original cell lysate sample. In order to have positive interaction do I have to be able to concentrate the target protein? So, what do you think, are these two proteins interacting ...
Drug synergy can be expressed not only as an additive effect, but also as potentiation, ie, substances combined effect is greater than the sum of effects of individual drugs.. In addition, allocate direct and indirect synergies, direct - drugs have a single point of application, an indirect - when the drugs have a different point of application and at the effect of indirectly affect each other.. additive method of drug therapy is widespread in modern medical practice, for example, the introduction of non-narcotic analgesics.Also found their other synergies.For example, the potentiation is used for the introduction of chlorpromazine and drugs for anesthesia.Chlorpromazine, providing a potentiating effect on drugs for anesthesia, to reduce their dosage.Indirect and indirect kinds of synergies are used to treat diabetes and asthma.. additive effect when used properly can be an excellent tool in the treatment of a large variety of diseases.At the same time it will help to heal even those diseases ...
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[Increasing experimental and clinical evidences demonstrated the synergic effect between the rapidly implemented immunotherapy and advanced forms of focal radiotherapy, not only on the elimination of the irradiated lesion, but also on the enhancement the immune-mediated systemic anti-tumoral activity. It is essential for gaining the most benefi t from the combination of the two modalities to select the appropriate patients, to defi ne the irradiation parameters, such as radiation quality (ie. particle) dosage, (total dose, fraction number) size of the target volume, the use of other supportive and anti-tumor drugs. In this review, we provide an update for the daily oncological practice on the data accumulated up to now on the molecular basis and patomechanism of enhancing radio-immune effect and clinical results, and highlight the most important parameters, which may increase the abscopal effect of ionizing radiation, thereby increasing the effectiveness of immunotherapy. However, development of
The goal of this clinical research study is to compare the safety and effectiveness of combining cytarabine with the study drug vosaroxin, versus cytarabine and a placebo, in treating patients with relapsed or refractory AML. Researchers want to compare how long these 2 study drug combinations may be able to help control the disease.
Vytorin is used in combination with proper diet to treat high cholesterol and triglyceride levels in the blood. This drug combination may help prevent medical problems caused...
Radiotherapy (RT), the major anti-cancer modality for more than half of cancer patients after diagnosis, has the advantage of local tumor control with relatively less systematic side effects comparing to chemotherapy. However, the efficacy of RT is limited by acquired tumor resistance leading to the risks of relapse and metastasis. To further enhance the efficacy of RT, with the renaissances of targeted immunotherapy (TIT), increasing interests are raised on RT combined with TIT including cancer vaccines, T-cell therapy, and antibody-based immune checkpoint blockers (ICB) such as anti-CTLA-4 and anti-PD1/PD-L1. In achieving a significant synergy between RT and TIT, the dynamics of radiation-induced response in tumor cells and stromal cells, especially the cross-talk between tumor cells and immune cells in the irradiated tumor microenvironment (ITME) as highlighted in recent literature are to be elucidated. The abscopal effect refereeing the RT-induced priming function outside of ITME could be ...
Fulltext - Comparative Evaluation of Zinc and Lead and their Synergistic Effects on Growth and Some Physiological Responses of Hassawi Okra (Hibiscus esculentus) Seedlings Ping Chen, Tao Hu, Yupei Liang, Yanan Jiang, Yongfu Pan, Chunjie Li, Ping Zhang, Dongping Wei, Pei Li, Lak Shin Jeong, Yiwei Chu, Hui Qi, Meng Yang, Robert...
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Recent tumor sequencing data suggest an urgent need to develop a methodology to directly address intratumoral heterogeneity in the design of anticancer treatment regimens. We use RNA interference to model heterogeneous tumors, and demonstrate successful validation of computational predictions for how optimized drug combinations can yield superior effects on these tumors both in vitro and in vivo. Importantly, we discover here that for many such tumors knowledge of the predominant subpopulation is insufficient for determining the best drug combination. Surprisingly, in some cases, the optimal drug combination does not include drugs that would treat any particular subpopulation most effectively, challenging straightforward intuition. We confirm examples of such a case with survival studies in a murine preclinical lymphoma model. Altogether, our approach provides new insights about design principles for combination therapy in the context of intratumoral diversity, data that should inform the ...
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The working together of two things to produce an effect greater than the sum of their individual effects. The theological doctrine that salvation results from the interaction of human will and divine grace.
Mei, S. (2012) Multi-Kernel Transfer Learning Based on Chous PseAAC Formulation for Protein Submitochondria Localization. Journal of Theoretical Biology, 293, 121-130.
The UNITY study has introduced the promising new drug combination of umbralisib plus ublituximab as a CLL treatment option. Learn more!
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In the article by H. Veldstra on Synergism and Potentiation which appeared in Pharmacological Reviews, volume 8, number 3, September 1956, the left half of figure 1 on page 344 was inadvertently omitted.. The complete figure 1 and its legend, reproduced below, should be substituted for the incomplete figure which appeared in the Journal.. ...
Chou, Y. R., Lo, W. C., Dubey, N. K., Lu, J. H., Liu, H. Y., Tsai, C. Y., Deng, Y. H., Wu, C. M., Huang, M. S. & Deng, W. P., 二月 15 2021, 於: Aging. 13, 3, p. 3605-3617 13 p.. 研究成果: 雜誌貢獻 › 文章 › 同行評審 ...
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"". Peyrat-Maillard, M. N.; Cuvelier, M. E.; Berset, C. (2003). "Antioxidant activity ... It is a negative type of synergism. Experiments with different combinations show that binary mixtures of phenolics can lead to ... Indian dental academy (2013-12-04). "Drug receptor interactions". Cite journal requires ,journal= (help) "Pharmacodynamics. ...
It is made up of the following four drugs: FOL - folinic acid (leucovorin), a vitamin B derivative that enhances the effects of ... FOLFIRI FOLFOX FOLFOXIRI IFL Moran, R. G.; Keyomarsi, K. (1987). "Biochemical rationale for the synergism of 5-fluorouracil and ... In 2013, the U.S. Food and Drug Administration approved protein-bound paclitaxel (also known as nab-paclitaxel, sold as ... FOLFIRINOX is a potentially highly toxic combination of drugs with serious side effects, and only patients with good ...
The method has been applied in the combination of anti-cancer drugs, anti-HIV agents, drug-radiation, and traditional Chinese ... The CI Value quantitatively defines synergism (CI. 1).[citation needed] Based on the above MEE and CI algorithms, a plot of CI ... The DRI is a measure of how many folds the dose of each drug in a synergistic combination may be reduced, at a given effect ..., free download). Entering a series of "dose (D) and effect (fa)" into computer for each drug alone and their ...
Drug delivery is the next step beyond the basic addition of growth factors to nerve guidance conduits. Many biomaterials used ... Synergism often occurs when two elements are combined; it is an interaction between two elements that causes an effect greater ... Investigation of synergism is the next step after individual techniques have proven to be successful by themselves. The ... Synergism is evident in the combining of scaffold material and topography with cellular therapies, neurotrophic factors, and ...
The most important part of this combination therapy, however, is the synergism between the drugs. While researchers are not ... Although this drug still cannot strictly target cancer cells, cancer cells have a higher average turnover of microtubules ... Prednisone, the last drug in the CHOP combination therapy is a corticosteroid that acts as an immunosuppressant.[citation ... This also allows for patients to receive lower and fewer doses of the drug and experience fewer side effects. Newer cases are ...
... drugs altering the composition of the human microbiome, drug metabolism by microbial enzymes modifying the drug's ... Synbiotics refers to food ingredients or dietary supplements combining probiotics and prebiotics in a form of synergism. The ... More than 30 drugs have been shown to be metabolized by gut microbiota. The microbial metabolism of drugs can sometimes ... and microbial drug metabolism affecting a drug's clinical efficacy and toxicity profile. Apart from carbohydrates, gut ...
By the time Yao Campos died on May 4, 2006, UNILAB had become the Philippines' largest drug-manufacturing company. UNILAB is ... The keys were product sourcing and planning, synergism in promotions and distribution outreach." By 1959, after only fourteen ... local drug manufacturers. This was attributed to the values Yao Campos was said to have instilled in the company, which ... years in operation, Yao Campos and Tan, with the help of Yao Campos' brother-in-law Dee, had transformed United Drug into ...
Owing to synergism between remifentanil and hypnotic drugs (such as propofol) the dose of the hypnotic can be substantially ... Drug Discovery and Development, Drug Discovery, 1, 339. Gatlin, Larry Alan, Shirley Ann Heiman, and Janet Sue Lewis. "Stable ... US Food and Drug Administration. (2010). Orange book: approved drug products with therapeutic equivalence evaluations. Silver ... due to synergism between remifentanil and various hypnotic drugs and volatile anesthetics. Remifentanil is used as an opioid ...
Infection and Drug Resistance. 13: 2485-2493. doi:10.2147/IDR.S258639. PMC 7383015. PMID 32801787. Hoyer, FF; Zhang, X; Coppin ... synergism with monocyte chemotactic protein-1 and -3". The Journal of Immunology. 157 (10): 4664-4671. PMID 8906847. Gómez-Rial ...
The drug was subsequently repurposed for use in the treatment of metastatic breast cancer and Cushing's syndrome. Amphenone B ... Jawetz E, Gunnison JB (1952). "Quantitative aspects of antibiotic synergism and antagonism". The American Journal of Medicine. ... As such, early publications of amphenone B, and some subsequent publications, refer to the drug by the incorrect structure. ... In healthy subjects and patients with adrenocortical carcinoma, the drug was found to be effective in decreasing circulating ...
The drug is contraindicated in patients with known hypersensitivity to Vibegron itself or single components of the drug. The ... known as synergism. The addition of darifenacin to vibegron created greater bladder relaxation only when used at high doses. ... Risk assessment for the drug in pregnant women has yet to be evaluated. Vibegron is in contrast to other OAB drugs very ... Clinical studies show no significant drug-drug interaction (DDI), aside from a serum concentration increase of digoxin when ...
... insights into drug action and drug discovery" (PDF). Nature Reviews. Endocrinology. 12 (6): 337-46. doi:10.1038/nrendo.2016.51 ... "Transcriptional activation by hepatocyte nuclear factor-1 requires synergism between multiple coactivator proteins". The ... The cause of hyperglycemia appears to alter the response to hypoglycemic drugs. Accordingly, HNF-1α-induced diabetes has marked ... Drug Metabolism and Disposition. 29 (5): 623-33. PMID 11302926. Rufibach LE, Duncan SA, Battle M, Deeb SS (July 2006). " ...
Jia Jia et al: "Mechanisms of drug combinations: interaction and network perspectives." Nature Reviews Drug Discovery 8, 111- ... According to the Synergism Hypothesis, synergistic effects have been the drivers of cooperative relationships of all kinds and ... The cooperative action of two or more stimuli (or drugs), resulting in a different or greater response than that of the ... Peter A. Corning, The Synergism Hypothesis: A Theory of Progressive Evolution, New York, McGraw Hill 1983 ISBN 0-07-013166-X; ...
Tables are available to check for drug interactions due to P450 interactions. An example of synergism is two drugs that both ... effects between either a drug and a disease two drugs Antagonism effects between either a drug and a disease two drugs Various ... of patients had an adverse drug reaction to at least one drug, and pharmacist involvement helps to pick up adverse drug ... An adverse drug event (ADE) refers to any injury occurring at the time a drug is used, whether or not it is identified as a ...
Covelli V, Passeri ME, Leogrande D, Jirillo E, Amati L (2005). "Drug targets in stress-related disorders". Curr. Med. Chem. 12 ... evidence for synergism between serotonergic and noradrenergic reuptake inhibition". Neuropharmacology. 51 (7-8): 1172-80. doi: ... Kulmatycki KM, Jamali F (2006). "Drug disease interactions: role of inflammatory mediators in depression and variability in ... and the drug Cytoxan, which unconditionally induces nausea and taste aversion and suppression of immune function. Ader was ...
This suggests that there are two ways to relieve anxiety in humans with serotonergic drugs: by blocking stimulation of 5-HT2A ... Evidence for synergism between serotonergic and noradrenergic reuptake inhibition". Neuropharmacology. 51 (7-8): 1172-80. doi: ... Other animal research suggests that long term drug-induced antidepressants effects modulate the expression of genes mediated by ... Kulmatycki, Kenneth M.; Jamali, Fakhreddin (2006). "Drug disease interactions: Role of inflammatory mediators in depression and ...
... illuminated mechanisms of drug resistance and synergism, deciphered the structural basis for antibiotic selectivity and showed ... how it plays a key role in clinical usefulness and therapeutic effectiveness, thus paving the way for structure-based drug ...
... prodrugs because of the need to consider drug developability issues in developing CO-based therapeutics Based on the synergism ... Carbon monoxide releasing materials (CORMAs) are essentially novel drug formulations and drug delivery platforms which have ... Drug Discovery. 9 (9): 728-43. doi:10.1038/nrd3228. PMID 20811383. Mahan VL (December 2012). "Neuroprotective, neurotherapeutic ... Critical Drug Delivery and Developability Issues" J. Pharm. Sci. 2016, 105, 406-416. PMID: 26869408). These CO prodrugs have ...
... such as a drug (see Synergy § Biological sciences) something relating to the theological position of synergism Synergy ( ...
... drug antagonism MeSH G12.361.477 - drug synergism MeSH G12.361.511 - food-drug interactions MeSH G12.361.755 - herb-drug ... drug resistance, fungal MeSH G12.392.269.383.500 - drug resistance, multiple, fungal MeSH G12.392.269.420 - drug resistance, ... drug resistance, multiple, fungal MeSH G12.392.300.750 - drug resistance, multiple, viral MeSH G12.392.395 - drug resistance, ... drug resistance, multiple MeSH G12.392.300.500 - drug resistance, multiple, bacterial MeSH G12.392.300.625 - ...
... potentially dangerous synergism. Eluxadoline increases the concentrations of drugs which are OATP1B1 and BCRP substrates. Also ... "Viberzi Information from". Retrieved 2015-06-01. Lembo AJ, Lacy BE, Zuckerman MJ, Schey R, Dove LS, ... The drug originated from Janssen Pharmaceutica and was developed by Actavis. This drug is contraindicated in case of having: ... In March 2017, the U.S. Food and Drug Administration issued a safety alert for eluxadoline concerning an increased risk of ...
The emergence of krokodil and excessive injuries among people who inject drugs in Eurasia". International Journal of Drug ... Lethal synergism between influenza virus and pneumococcus, causes excess mortality from secondary bacterial pneumonia during ... Drug and Alcohol Dependence (in press). González-Guarda Rosa; Florom-Smith A.; Thomas T. (2011). "A syndemic model of substance ... Singer, Merrill 2008 Drug-related Syndemics and the Risk Environment: Assessing Street risk among Hispanics in Hartford. ...
In animal studies, SR-142948 blocked the effects of stimulant drugs, including MDMA. Nalivaiko E, Michaud JC, Soubrié P, Le Fur ... "Blockade of neurotensin receptors suppresses the dopamine D1/D2 synergism on immediate early gene expression in the rat brain ... SR-142948 is a drug used in scientific research which is a non-peptide antagonist selective for the neurotensin receptors, ...
... (CR-1409) is a drug which inhibits gastrointestinal motility and reduces gastric secretions, acting as a ... synergism with pharmacological levels of melatonin". Journal of Pineal Research. 39 (3): 243-50. doi:10.1111/j.1600-079X. ... Expert Opinion on Investigational Drugs. 9 (1): 129-46. doi:10.1517/13543784.9.1.129. PMID 11060666. Herranz R (September 2003 ...
An example of synergism is two drugs that both prolong the QT interval. ... An adverse drug event (ADE) refers to any injury occurring at the time a drug is used, whether or not it is identified as a ... of patients had an adverse drug reaction to at least one drug, and pharmacist involvement helps to pick up adverse drug ... Textbook of adverse drug reactions. Oxford: Oxford University Press, 1977:10. *^ Aronson JK. Drug therapy. In: Haslett C, ...
". "Isradipine and Anzemet Drug Interactions". "Isradipine and Onmel Drug Interactions". "Isradipine and Zanaflex Drug ... demonstrates anti-hypertensive effects and should be avoided in patients taking Isradipine due to the possibility of synergism ... CS1 maint: discouraged parameter (link) MedlinePlus DrugInfo medmaster-a693048 Diseases Database (DDB): 30003 Drug offers hope ... drug substitution study". J Clin Hypertens (Greenwich). 7 (4 Suppl 1): 27-31. doi:10.1111/j.1524-6175.2005.04450.x. PMID ...
It is possible that RFA followed by radiation therapy has a survival benefit due to synergism of the two mechanisms of cell ... In 2015, the US Food and Drug Administration (FDA) approved the anti-PD-1 agent nivolumab for advanced or metastatic SCC. In ... Farmer (2010). "Non-Small-Cell Lung Cancer Standards of Care Challenged by a Cornucopia of New Drugs". Sandler A, Gray R, Perry ... Roughly 10-35% of people who have NSCLC will have drug-sensitizing mutations of the EGFR. The distribution of these mutations ...
"On Synergism of Potassium and Magnesium in Maintenance of Myocardial Function". PMID 28294893. Cite journal requires ,journal ... together with potassium gluconate in the drug Rhythmocor is used to treat heart disease. Pilot studies have shown efficacy in ...
Penicillin remains the drug of choice for treating streptococcal infections, and S.dysgalactiae strains with reduced ... Baker, C. N.; Thornsberry, C.; Facklam, R. R. (1981-05-01). "Synergism, killing kinetics, and antimicrobial susceptibility of ...
Milnacipran's lack of drug-drug interactions via cytochrome P450 enzymes is thought to be an attractive feature because many of ... which give the impression that synergism is an efficient property in mediating antidepressant activity. ... Symptoms of SNRI overdose, whether it be a mixed drug interaction or the drug alone, vary in intensity and incidence based on ... Overdosing on SNRIs can be caused by either drug combinations or excessive amounts of the drug itself. Venlafaxine is ...
Also, when chemotherapy is given after birth, many of the drugs appear in breast milk, which could harm the baby.[219] ... "Disruption of Brca2 increases the spontaneous mutation rate in vivo: synergism with ionizing radiation". EMBO Reports. 3 (3): ... Chemotherapy is the treatment of cancer with one or more cytotoxic anti-neoplastic drugs (chemotherapeutic agents) as part of a ... Winther H, Jorgensen JT (2010). "Drug-Diagnostic Co-Development in Cancer". Pharm Med. 24 (6): 363-75. doi:10.2165/11586320- ...
"Drug Topics, February 18, 2008. Retrieved 2008-10-23.. "Top 200 brand drugs by units in 2007". Drug Topics, February 18, 2008. ... Evidence for synergism between serotonergic and noradrenergic reuptake inhibition". Neuropharmacology. Elsevier. 51 (7-8): 1172 ... Yuferov V, Butelman E, Kreek M (2005). "Biological clock: biological clocks may modulate drug addiction". Eur J Hum Genet. 13 ( ... "Drug Combos Linked To Breast Cancer Risk". CBS News. 2009-05-30.. ...
Drug-Diagnostic Co-Development in Cancer»։ Pharm Med 24 (6): 363-75։ 2010։ doi:10.2165/11586320-000000000-00000 (inactive 2018- ... Disruption of Brca2 increases the spontaneous mutation rate in vivo: synergism with ionizing radiation»։ EMBO Reports 3 (3): ... Nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors for primary prevention of colorectal cancer: a systematic ...
SH3 domain-mediated protein-protein interaction blocking drug". Oncogene (England) 21 (13): 2037-50. ISSN 0950-9232. PMID ... "Transcriptional activation by hepatocyte nuclear factor-1 requires synergism between multiple coactivator proteins". J. Biol. ...
"Drug Discov Today 15 (23-24): 1052-7. PMID 20970519. doi:10.1016/j.drudis.2010.10.003. edit ... "Anti-HIV activity of olive leaf extract and synergism with HAART". Int Conf AIDS 15th. Bangkok. ... 2012). "ChEMBL: a large-scale bioactivity database for drug discovery". Nucleic Acids Res 40 (Database issue): D1100-7. PMID ... "PubChem as a public resource for drug discovery.". ...
Cardiovascular Drugs and Therapy. 12 Suppl 2 (2suppl): 197-202. doi:10.1023/A:1007708918683. PMID 9794094.. ... The cells do not lose all their fight-or-flight override because of interleukin-1's synergism with CRH. Cortisol even has a ...
Sequential application of drugs can lead to the sequential evolution of resistance mutations to each drug in turn.[102] ... "Disruption of Brca2 increases the spontaneous mutation rate in vivo: synergism with ionizing radiation". EMBO Rep. 3 (3): 255- ... Resistance to BCR-ABL targeting drugs[edit]. In the case of Gleevec (Imatinib), which targets the BCR-ABL fusion gene in ... Cancer treatment drugs pose a strong selective force on all types of cells in tumors, including cancer stem cells, which would ...
This evolution is why cancer recurrences will have cells that have acquired cancer-drug resistance (or in some cases, ... "Disruption of Brca2 increases the spontaneous mutation rate in vivo: synergism with ionizing radiation". EMBO Reports. 3 (3): ... or how HIV can become drug-resistant), and the same reason why crop blights and pests can become pesticide-resistant. ...
drug transmembrane transport. • quaternary ammonium group transport. • acetate ester transport. • cation transport. • ion ... Tomilin A, Reményi A, Lins K, Bak H, Leidel S, Vriend G, Wilmanns M, Schöler HR (December 2000). "Synergism with the ... Rosilio, C; Ben-Sahra, I; Bost, F; Peyron, JF (1 May 2014). "Metformin: a metabolic disruptor and anti-diabetic drug to target ... and other organs are critical for elimination of many endogenous small organic cations as well as a wide array of drugs and ...
1196-. ISBN 978-0-7817-1750-2. Sarah H. Wakelin; Howard I. Maibach; Clive B. Archer (21 May 2015). Handbook of Systemic Drug ... the authors of the study attributed the breast development to a synergism of her high, supraphysiological IGF-1 levels with the ... Jeffrey K. Aronson (2 March 2009). Meyler's Side Effects of Cardiovascular Drugs. Elsevier. pp. 255-. ISBN 978-0-08-093289-7. ... 256-. ISBN 978-0-7637-3075-8. Bowman JD, Kim H, Bustamante JJ (2012). "Drug-induced gynecomastia". Pharmacotherapy. 32 (12): ...
Milnacipran's lack of drug-drug interactions via cytochrome P450 enzymes is thought to be an attractive feature because many of ... which give the impression that synergism is an efficient property in mediating antidepressant activity. ... Symptoms of SNRI overdose, whether it be a mixed drug interaction or the drug alone, vary in intensity and incidence based on ... Serotonin syndrome can be caused by taking multiple serotonergic drugs, such as SSRIs or SNRIs. Other drugs that contribute to ...
Can structures lead to better drugs? Lessons from ribosome research // From molecules to medicines / J. L. Sussman, and P. ... Antibiotics targeting ribosomes: resistance, selectivity, synergism, and cellular regulation (англ.) // Annual Review of ...
Also, when chemotherapy is given after birth, many of the drugs appear in breast milk, which could harm the baby.[227] ... "Disruption of Brca2 increases the spontaneous mutation rate in vivo: synergism with ionizing radiation". EMBO Reports. 3 (3): ... Chemotherapy is the treatment of cancer with one or more cytotoxic anti-neoplastic drugs (chemotherapeutic agents) as part of a ... The term encompasses a variety of drugs, which are divided into broad categories such as alkylating agents and antimetabolites. ...
It functions as a major molecular target for the immunosuppressive drugs such as ciclosporin. Five transcript variants encoding ... "Human immunodeficiency virus type-1 tat enhances interleukin-2 promoter activity through synergism with phorbol ester and ...
Drug Topics, 18 Februari 2008. Iliwekwa mnamo 2008-10-23. Top 200 brand drugs by units in 2007.. Drug Topics, 18 Februari 2008 ... Evidence for synergism between serotonergic and noradrenergic reuptake inhibition". Neuropharmacology (Elsevier) 51 (7-8): 1172 ... 14.0 14.1 14.2 14.3 López-Muñoz F, Alamo C, Juckel G, Assion HJ (2007). "Half a century of antidepressant drugs: on the ... Yuferov V, Butelman E, Kreek M (2005). "Biological clock: biological clocks may modulate drug addiction". Eur J Hum Genet 13 ( ...
By the late Middle Ages, the term "sodomy" had come to cover copulation between males, bestiality, non-vaginal heterosexual intercourse,[7] coitus interruptus, masturbation, fellatio and anal sex (whether heterosexual or homosexual);[33] and it increasingly began to be identified as the most heinous of sins by authorities of the Catholic Church. In Italy, Dominican friars would encourage the pious to "hunt out" sodomites and hand them to the Inquisition to be dealt with accordingly: "These clerical discourses provided a language for secular authorities to condemn sodomy, ...By persecuting sodomites as well as heretics, the Church strengthened its authority and credibility as a moral arbiter".[34] Pope Leo IX labeled homosexuality in the 11th century as "filthy," an "execrable vice," and "obscene."[35] Likewise around 1051, Peter Damian penned the Liber Gomorrhianus in which he argued for stricter ecclesiastical punishment for clerics guilty of "sins against nature".[35][36] Klaits writes: "From ...
It is managed by life prolonging drugs known as Antiretroviral drugs (ARVs). TB was discovered by Robert Koch in 1882. It is ... Scrimshaw NS, SanGiovanni JP (August 1997). "Synergism of nutrition, infection, and immunity: an overview". Am. J. Clin. Nutr. ... Of 1393 new drugs brought into use over a period of 25 years (1975-1999), only a total of thirteen, less than 1%, related to ... Of 20 MNC drug companies surveyed for research on PRDs, only two had projects targeted towards these neglected PRDs. However, ...
... new mechanisms for old drugs". N. Engl. J. Med. 353 (16): 1711-23. doi:10.1056/NEJMra050541. PMID 16236742. Hollenberg SM, ... "Selective binding of steroid hormone receptors to octamer transcription factors determines transcriptional synergism at the ...
It was found that providing combined cytotoxic drugs is better than a single drug; a process called the combination therapy; ... synergism with ionizing radiation". EMBO Reports. 3 (3): 255-60. doi:10.1093/embo-reports/kvf037. PMC 1084010. PMID 11850397. ... Also, when chemotherapy is given after birth, many of the drugs appear in breast milk, which could harm the baby. Veterinary ... Chemotherapy is the treatment of cancer with one or more cytotoxic anti-neoplastic drugs (chemotherapeutic agents) as part of a ...
... drugs is the poly(ADP-ribose) polymerase 1 (PARP1) inhibitor olaparib, which was approved by the Food and Drug Administration ... synergism with ionizing radiation". EMBO Reports. 3 (3): 255-60. doi:10.1093/embo-reports/kvf037. PMC 1084010. PMID 11850397. ... Many other drugs for use against other residual DNA repair mechanisms commonly found in cancer are currently under ...
It was used mainly in the treatment of stomach ulcers, although it has now been largely replaced by newer drugs for this ... synergism with pharmacological levels of melatonin". Journal of Pineal Research. 39 (3): 243-50. doi:10.1111/j.1600-079X. ... This can make it a useful adjuvant treatment to use alongside opioid drugs in the treatment of chronic pain conditions such as ... An interesting side effect of proglumide is that it enhances the analgesia produced by opioid drugs, and can prevent or even ...
After the GUSTO studies, rt-PA became the thrombolytic drug of choice for most of the cardiologists in the Western world and ... Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma ... Genentech immediately started to market the drug in the US under the brand name Activase®, while Boehringer Ingelheim would ... from a laboratory concept to the first life saving biotech drug. Recombinant t-PA has been primarily used for dissolving blood ...
From 1985 to 1987, Wilkinson worked for Wellcome Research Laboratories and Beecham in the area of drug discovery. He was one of ... synergism in nature; New exotic fruits and their unique nutritional properties. Dr Wilkinson obtained the first novel food ... and synergism in botanical medicines, botanical foods and ecological biochemistry, and who led the first European degree course ... The only comprehensive guide to more than 6,000 prescription and over the counter drugs, herbs and supplements and their ...
Under 2003 U.S. Food and Drug Administration regulations, when monosodium glutamate is added to a food, it must be identified ... While research has shown that this synergism occurs in some animal species with other amino acids, studies of human taste ... In 1959, the Food and Drug Administration classified MSG as a "generally recognized as safe" (GRAS) food ingredient under the ... U.S. Food and Drug Administration. November 19, 2012. Tarasoff L.; Kelly M.F. (1993). "Monosodium L-glutamate: a double-blind ...
The interaction index: a measure of drug synergism.. Tallarida RJ1.. Author information. 1. Department of Pharmacology and ... Two drugs used in combination may produce enhanced or reduced effects. The degree of enhancement or reduction is measured from ... In some cases, the relative potency of the constituent drugs is the same at all effect levels. When this is so, it is shown ... The index is therefore a quantitative marker for the drug combination and effect metric used. Methodology for measuring the ...
proportion of total that is drug A. pB proportion of total that is drug B. fA fraction of potency of drug A. fB fraction of ... Each showed significant synergism for this drug pair and also showed that the degree of synergism, measured as the interaction ... If drug B is the reference drug, then the combination is equivalent to a/R + b, and that quantity is used in drug Bs dose- ... dose (or concentration) of drug A. α. interaction index. B. dose (or concentration) of drug B. R. relative potency. (a. b), ...
Coencapsulation of two drugs into liposomes can "synchronize" the distribution of the drugs if the drugs can be stably ... liposomal drug by breaking down the liposomes. Given the inherent differences between drugs, coencapsulated drug may be ... Liposomal delivery as a mechanism to enhance synergism between anticancer drugs Message Subject (Your Name) has forwarded a ... Liposomal delivery as a mechanism to enhance synergism between anticancer drugs. Robert J. Lee ...
Synergism of Curcumin and Cytarabine in the Down Regulation of Multi-Drug Resistance Genes in Acute Myeloid Leukemia. Author(s ... Title:Synergism of Curcumin and Cytarabine in the Down Regulation of Multi-Drug Resistance Genes in Acute Myeloid Leukemia ... "Synergism of Curcumin and Cytarabine in the Down Regulation of Multi-Drug Resistance Genes in Acute Myeloid Leukemia", Anti- ... Letters in Drug Design & Discovery. *Molecular Targets of Omega-3 Fatty Acids for Cancer Therapy. Anti-Cancer Agents in ...
Laser Synergism with Drug Eluting Balloon for Treatment of In-Stent Restenosis in the Lower Extremities. ... van den Berg J.C. (2015) Laser Synergism with Drug Eluting Balloon for Treatment of In-Stent Restenosis in the Lower ... Drug eluting balloons. Tech Vasc Interv Radiol. 2010;13(1):59-63.CrossRefPubMedGoogle Scholar ... Drug-eluting balloon: very short-term exposure and overlapping. Thromb Haemost. 2009;101(1):201-6.PubMedGoogle Scholar ...
First, we describe a cell-based assay to assess the synergism between anticancer mAb and cytotoxic drugs, that uses the ... CI values of ,1 indicate synergism between tested mAbs and cytotoxic agents 1. To corroborate the in vitro findings in vivo, we ... This protocol allows the effective evaluation of anticancer drug combinations in preclinical models and the identification of ... combination index equation of Chou and Talalay 1. This includes the measurement of tumor cell drug-and antibody-sensitivity ...
The drug combination effects were analyzed by the Chou-Talalay method.. Results: Six compounds were successfully identified ... The drug combination effects were analyzed by the Chou-Talalay method.. Results: Six compounds were successfully identified ... Methods: A Sensitivity Index (SI)-based drug combination screening method was established to evaluate the interactions between ... Methods: A Sensitivity Index (SI)-based drug combination screening method was established to evaluate the interactions between ...
antiatherosclerotic drugs, antihypertensive drugs, medicines for Alzheimers disease treatment and for multiple sclerosis, ... Our research one of most perspective way to create such medicines based on the synergy already registered and studied drugs in ... Developed by our team directions already given concrete results: produced veterinary dynamic antiviral drug with wide action ... Research continues dynamic anti-cancer drug, synergistic kvasi-living antibiotics,. ...
Drug synergism analysis. The raw data for drug synergism analysis were generated by the MTT assay. The cells were evenly plated ... Right: Drug synergism analysis showing synergism index on different FA with the dosage ratio of 4:1 (LAP:ABE). g Western blots ... b Drug synergism analysis showing synergism index on different FA (fraction affected) in TNBC cell lines. Dosage ratio: LAP:ABE ... Chou, T.-C. Drug combination studies and their synergy quantification using the Chou-Talalay method. Cancer Res. 70, 440-446 ( ...
"Drug Synergism" by people in this website by year, and whether "Drug Synergism" was a major or minor topic of these ... "Drug Synergism" is a descriptor in the National Library of Medicines controlled vocabulary thesaurus, MeSH (Medical Subject ... Below are the most recent publications written about "Drug Synergism" by people in Profiles. ... Below are MeSH descriptors whose meaning is more general than "Drug Synergism". ...
The MRSA test strains were found to be multi-drug resistant and also exhibited high level of resistance to common beta-lactam ...
WebMD In the 15p read drug synergism and, it is substantial value as it applies a joint agenda in the elementary device of the ... State of Illinois; The read drug synergism will use 65 topics. L: lower Value of the existing chart i: time of the other ... Cook County An read drug synergism and dose in & provided him to a standard with the Asymmetry of Spinoza, one future of which ... Firm Practice Areas A exterior read drug synergism and dose effect data to this algorithm has to honour a language case for ...
The substrate range of drug efflux pumps is not limited to antibiotics, but it also includes toxins, dyes, detergents, lipids, ... The substrate range of drug efflux pumps is not limited to antibiotics, but it also includes toxins, dyes, detergents, lipids ... on the structure determination and functional analysis of the AcrB and MexB components of the AcrAB-TolC and MexAB-OprM drug ... on the structure determination and functional analysis of the AcrB and MexB components of the AcrAB-TolC and MexAB-OprM drug ...
Drug Des. Discov. 2006, 3, 443-451. [Google Scholar] [CrossRef]. *Hussain, S.F.; Yang, D.; Suki, D.; Aldape, K.; Grimm, E.; ... Goldie, J.H. Drug resistance in cancer: A perspective. Cancer Metastasis Rev. 2001, 20, 63-68. [Google Scholar] [PubMed] ... Pak, B.J.; Chu, W.; Lu, S.J.; Kerbel, R.S.; Ben-David, Y. Lineage-specific mechanism of drug and radiation resistance in ... Those who have MGMT positive tumors can also benefit from the synergism of TMZ and radiotherapy when O6-benzylguanine is added ...
Drug: Pectin Patients allocated to experiment group will receive 12 g pectin each day for 12 weeks. ... Evaluating the Synergism of Soluble Dietary Fiber With Fecal Microbiota Transplantation in Slow Transit Constipation. The ... The purpose of this study is to evaluate the synergism of Soluble Dietary Fiber with Fecal Microbiota Transplantation in Adult ... A Randomized, Controlled Study of Synergism of Soluble Dietary Fiber With Fecal Microbiota Transplantation in Adult Patients ...
Drug Synergism Evaluation. To determine potential synergistic drug effects on growth of CSCs GBM1, GBM2, and GBM3, cells were ... As compared to single drug treatments, the drug combination increased the percentage of apoptotic cells (GBM2: 41.27% of early+ ... Anticancer Drug Discov. 10, 145-162. doi: 10.2174/1574892810666150317144511. PubMed Abstract , CrossRef Full Text , Google ... Isobolograms of drug combination on GBM1, GBM2, and GBM3 CSC viability after treatment for 48 and 72 h, are represented. ...
Kidney transplant drug halves the early risk of organ rejection * Meta-analysis shows that alteplase given promptly after ... New research highlights potential cardiovascular risk of novel anti-osteoporotic drug * Work begins on UK system for estimating ... New heart disease drug to be made available to NHS patients through ground-breaking collaboration ... Richard Doll Seminar: Insights into stroke genetics - Balancing quantity with quality to inform discovery & drug targets ...
The resurgent idea that multi-component drug therapy might be better than monotherapy is illustrated by the recent resolution ... Flavonoids from Artemisia annua L. as antioxidants and their potential synergism with artemisinin against malaria and cancer ...
... and a possible synergism with other risk factors such as NSAIDs intake, have never been investigated. In this case-control ... and bleeding from these lesions is frequently related to intake of non-steroidal anti-inflammatory drugs (NSAIDs) [2]. In ... 2011) Synergism between Prior Anisakis simplex Infections and Intake of NSAIDs, on the Risk of Upper Digestive Bleeding: A Case ... In the present study, the observed synergism between NSAID consumption and prior Anisakis infections on the risk of UGIB were ...
Synergism. Drugs can also interact when they have the same intended effect or complementary effects. For instance, this can ... Specific drug interactions. This table[6] lists common drugs used to treat diabetes as well as other drugs commonly used by ... Bring a list of all of the drugs you take (or simply bring the drugs themselves), including prescription drugs, over-the- ... The most common form of drug interaction occurs when one drug interferes with another drugs elimination from the body. ...
Synergism; Drug-interaction; Comparative-toxicology ...
Drug synergism assay and analysis. HT55 and SW948 cells were seeded at concentration of 105 cells per ml in a 96-well plate. ... A) Schematic of the drug screen protocol using YFP-1322 mice. (B) Column graphs of the effect of candidate drugs on organoid ... Drug screen compounds and other reagents. HGF (R&D), Dkk1 (R&D), Wif1 (R&D), Draxin (R&D), sFRP1 (R&D), sFRP5 (R&D), BMP4 (R&D ... From the drug screen, as a result of the limited numbers of cells present in wells treated with high dose (2.5 µM) itraconazole ...
Synergism was observed when drug combinations were tested in vitro, notably with fumagillin and terramycin and with fumagillin ... Drug Effects on the Metabolism of Endamoeba Histolytica; in Vitro and in Vivo Tests of Synergism * Authors: Mitsuru Nakamura, ... Synergism was observed when drug combinations were tested in vitro, notably with fumagillin and terramycin and with fumagillin ...
Numerous natural products have also exhibited potent synergism against the drug-resistant bacteria when used in combination ... Recently, several antibacterials derived from microbes have been developed and approved by Food and Drug Administration (FDA) ... making the target bacteria susceptible to these drugs again. ... Drug resistance developed in human pathogenic bacteria is ... have demonstrated multiple biological activities in biomedical areas including their antibacterial actions against various drug ...
synergism, synergy the joint action of agents, as drugs, that, taken together, produce a greater effect than the sum of their ... 2 . the place where drugs are prepared, dispensed, or sold. Also called apothecary . 3 . a drug therapy. - pharmacist , n . ... 2 . a pharmacists stock of drugs. pharmacopolist an apothecary or pharmacist. pharmacy 1 . the art of preparing drugs and ... 1 . the narcosis or narcoma induced by drugs. 2 . an addiction to drugs. opiomania an addiction to opium. opiophagism, ...
... additive responses anticipated from drug combos or a unmarried drugs interplay with endogenous chemicals.In Drug Synergism and ... Download Drug Synergism and Dose-Effect Data Analysis by Ronald J. Tallarida PDF. September 29, 2017. by admin ... briefly, Drug Synergism and Dose-Effect information research has every thing you want to practice, with self belief, the ... Read Online or Download Drug Synergism and Dose-Effect Data Analysis PDF ...
... it is called synergism. Sulfa drugs and trimethoprim are a great example of drug synergism. ... Sulfa Drugs. Sulfa drugs are a class of synthetic drugs that all have a sulfonamide chemical group. These drugs have many ... Synergism With Trimethoprim. Thats why sulfa drugs are often administered in combination with trimethoprim, which is another ... Sulfa drugs like Sulfamethoxazole inhibit the enzyme that catalyzes the first step of this pathway. Sulfa drugs are competitive ...
The drug release mechanism was related with the surfactant/cosurfactant synergism, thus the lower efficiency of the tensides ... Microemulsions / Surfactant/cosurfactant synergism / Drug solubilization capacity / In vitro release testing (IVRT) / Ibuprofen ... The drug molecules were predominantly solubilized within the interface film. The amount of drug released from the formulations ... Investigation of surfactant/cosurfactant synergism impact on ibuprofen solubilization capacity and drug release characteristics ...
Nitazoxanide, a Novel Potential Anti-Influenza Drug, Acting in Synergism with Neuraminidase Inhibitors ... Resistance to current antiviral drugs underscore the need for additional therapies. Nitazoxanide (NTZ) and its active ...
Diuretic drugs usually improve edema when used judiciously. Some patients, however, become resistant to their effects. Diuretic ... When diuretic resistance is present, using a second diuretic drug that acts in a different nephron segment is often effective. ... Recent experimental results suggest that a second class of drug may act synergistically with the first by blocking the adaptive ... The Physiologic Basis of Diuretic Synergism: Its Role in Treating Diuretic Resistance. Ann Intern Med. 1991;114:886-894. doi: ...
  • Hence, a quantitative knowledge of drug combination pharmacology is important-in clinical settings and in all experiments aimed at studying mechanism. (
  • For comparison, in modern pharmacology rare to find drugs that contain more than five different active substances. (
  • the division of pharmacology concerned with the action and breakdown of drugs in the body. (
  • the branch of pharmacology that studies the composition, use, and history of drugs. (
  • Marginal notes on the quantitative pharmacology of combined drugs]. (
  • Much of the classic literature dealing with drug combinations is restricted to analyses in which the individual log dose-effect data are legitimately constrained by regression procedures that yield parallel lines ( Finney, 1942 , 1971 ). (
  • 9 ) have investigated the application of liposomes as a delivery vehicle for drug combinations. (
  • The use of drug combinations is a widely adopted strategy in clinical cancer therapy. (
  • This is very valuable because current drug combinations are evaluated empirically in the context of clinical trials. (
  • Liposomes carrying drug combinations exhibit pharmacokinetic properties of the carrier, such as long circulation, reticuloendothelial pathway of clearance, and enhanced permeability and retention-mediated tumor accumulation, which may enhance therapeutic efficacy and reduce toxicity of these drugs. (
  • A potential confounding factor in the liposomal codelivery of drug combinations, therefore, is that drug release from the liposomes may follow a different mechanism in vitro and in vivo . (
  • Nevertheless, stable coencapsulation synchronizes drug distribution at least to the point of extravasation from the vasculature, provides delivery of combinations of drugs at a specific ratio, and may provide unique therapeutic advantages through therapeutic synergism. (
  • It is conceivable such studies will yield many promising drug combinations with clinical potential. (
  • The ability of liposomal drug carrier to determine drug pharmacokinetics in vivo greatly enhanced the translational potential of drug combinations identified in vitro and thus provides a valuable tool for preclinical screening of drug combinations for clinical development. (
  • Conclusions: The screening method developed in this study demonstrated its usefulness in the rapid identification of synergistic drug combinations of PI3K inhibitors and targeted agents. (
  • But some drugs are not supposed to be taken simultaneously, and doctors and pharmacists don't always notice when a person is taking dangerous or risky drug combinations. (
  • Synergism was observed when drug combinations were tested in vitro , notably with fumagillin and terramycin and with fumagillin and thiocarbarsone (C.C. 914). (
  • We measured the phosphorylation of multiple proteins and cell viability in response to systematic drug combinations and derived computational models of the signaling network. (
  • The purpose of the chapter is to review those studies dealing with the empirical data describing the pharmacologic and behavorial effects of alcohol and drug combinations and also those studies which may illuminate the mechanisms of those interactions. (
  • Cell-based assays centered on these differences and using uncorrelated drug effects reveals novel synergistic combinations for the treatment of breast cancer dependent on PI3K-mTOR signaling. (
  • Fundamental cancer processes, pathways, and drivers contribute to this feature, which can also be exploited to predict precise synergistic drug combinations. (
  • Problems on the practice of the quantitative evaluation of drug combinations]. (
  • Let us briefly see the scientific rationale of such selected few drug combinations and their particular examples. (
  • All other drug-combinations are irrational and should not be allowed. (
  • 1) in drug combinations. (
  • It is important that preclinical studies of drug combinations present in full detail the interaction analytic approach ( 3 ). (
  • Background: The aim of the study was to find a role of Curcumin from natural source to overcome drug resistance as well as to reduce cytotoxicity profile of the drug in Acute Myeloid Leukemia patients. (
  • Krupa Shah, Sheefa Mirza, Urja Desai, Nayan Jain and Rakesh Rawal, "Synergism of Curcumin and Cytarabine in the Down Regulation of Multi-Drug Resistance Genes in Acute Myeloid Leukemia", Anti-Cancer Agents in Medicinal Chemistry (2016) 16: 128. (
  • The MRSA test strains were found to be multi-drug resistant and also exhibited high level of resistance to common beta-lactam antibiotics. (
  • Bad bugs in the XXIst century: resistance mediated by multi-drug efflux pumps in Gram-negative bacteria. (
  • Drug efflux protein complexes confer multidrug resistance on bacteria by transporting a wide spectrum of structurally diverse antibiotics. (
  • In this review we will explore how the available biochemical and structural information can be translated into the discovery and development of new compounds that could reverse drug resistance in Gram-negative pathogens. (
  • However, infections caused by Gram-negative pathogens proved much harder to treat due to the very high intrinsic drug resistance displayed by Gram-negative organisms. (
  • This intrinsic drug resistance is due to presence of an outer membrane which acts as a permeability barrier and by the expression of drug efflux pumps. (
  • Drug resistance developed in human pathogenic bacteria is emerging and has become a global problem. (
  • More promisingly, some natural products could reverse the resistance of bacteria to the antibiotics, making the target bacteria susceptible to these drugs again. (
  • Diuretic resistance may result from dietary indiscretion, poor compliance, impaired bioavailability, impaired diuretic secretion into the lumen of the renal tubule, or because other drugs interfere with diuretic activity. (
  • When diuretic resistance is present, using a second diuretic drug that acts in a different nephron segment is often effective. (
  • Resistance to current antiviral drugs underscore the need for additional therapies. (
  • Microbial Drug Resistance, 19 (4), 256-265. (
  • The main aims are to achieve synergistic therapeutic effect, dose and toxicity reduction, and to minimize or delay the induction of drug resistance ( 1 ). (
  • Toxicity reduction and resistance minimization benefits could also be the outcomes of synergism. (
  • The high activation of protein kinase B (AKT)/nuclear factor‑κB (NF‑κB) signaling has often been associated with the induction of non‑small cell lung cancer (NSCLC) cell survival and resistance to cisplatin, which is one of the most widely used chemotherapeutic drugs in the treatment of NSCLC. (
  • step by step functional how you can practice and interpret assays for drug metabolism and toxicity review are supplied, in addition to a comparability of other strategies on hand. (
  • Drug metabolism in ethanol induced fatty liver, Life Sci . (
  • One drug interfers with the metabolism of a second drug. (
  • What are the factors that affect drug metabolism? (
  • The process of drug movement to achieve drug action: Absorption, Distribution, Metabolism, and Excretion. (
  • Drugs are carried by blood and tissue fluids to: Action sites, metabolism sites, excretion sites. (
  • Various diseases, especially those that cause renal or hepatic insufficiency, may alter drug metabolism. (
  • Abnormal drug metabolism may be due to inherited factors of either Phase I oxidation or Phase II conjugation. (
  • Inheriting abnormal alleles of cytochrome P450 can alter drug metabolism. (
  • Inheriting abnormal N -acetyltransferase which conjugated some drugs to facilitate excretion may affect the metabolism of drugs such as isoniazid , hydralazine , and procainamide . (
  • Inheriting abnormal thiopurine S -methyltransferase may affect the metabolism of the thiopurine drugs mercaptopurine and azathioprine . (
  • [14] [15] These are mainly for drugs without much first-pass liver metabolism. (
  • Discovery of Drugs through Metabolism Studies 1.2.5. (
  • Methods: A Sensitivity Index (SI)-based drug combination screening method was established to evaluate the interactions between BKM120, a pan-PI3K inhibitor, and compounds from a library of 606 target-selective inhibitors. (
  • Many issues are due to drug-drug interactions, and despite the use of computerized prescription checking, they still are a major cause of hospitalization and death. (
  • In one study, the authors identified 133 potentially serious possible drug interactions for Type 2 diabetes, of which 25 (19 percent) involved one of the four drugs recommended as first-line treatments for all or nearly all patients. (
  • Not all potential drug interactions result in a bad outcome, but drug interactions contribute to an increased risk of an adverse event occurring. (
  • With all of the drugs on the market today, how many drug interactions are possible? (
  • Fortunately, while there are a lot of potential drug interactions, not all of them result in adverse drug reactions. (
  • These interactions run the gamut from antagonistic effects with mutual neutralization to simple addition of similar effects to actual potentiating interactions where the total effect of the two drugs is greater than the sum of the effects of the two drugs alone. (
  • The mechanisms of these interactions are even less well understood than those for the individual drugs. (
  • One might think the risk of drug interactions would be lower in the hospital, where patients are under close medical supervision, but the opposite is true: The problem is even greater for people admitted to a hospital. (
  • On average, a person who enters the hospital is treated with 10 drugs and has about a 20% probability of having a reaction caused by drug interactions. (
  • Tables are available to check for drug interactions due to P450 interactions. (
  • The risk of drug interactions is increased with polypharmacy . (
  • Topics include complicating problems involved in determining the effects of impulse noise , the potentiating effects of impulse noise plus continuous noise , the potentiating effect of noise plus vibration, and noise and drug interactions. (
  • To obtain an appropriate evaluation of two-drug interactions, a graph with all fractions is always preferred. (
  • Although drug interaction at different drug ratios can be systematically studied in vitro , these ratios cannot be easily translated in vivo due to differential pharmacokinetic characteristics of different drugs. (
  • The current study investigates the performances of the multicomponent mixtures of nonionic surfactants regarding the microemulsion stabilisation, drug solubilization and in vitro drug release kinetic. (
  • We demonstrated that time kill assay must be considered the gold standard method to detect synergism in vitro, as it allows greater dynamic assessment and higher sensitivity, when compared to the other methods. (
  • Combined use of the drugs inhibited tumor cell growth and proliferation in vitro in H1_DL2 cells, compared to single drug treatment. (
  • 2. the joint action of agents, as drugs, that when taken together increase each other's effectiveness (contrasted with antagonism ). (
  • The problem of synergism and antagonism of combined drugs. (
  • This theory also provides algorithms for automated computer simulation for synergism and/or antagonism at any effect and dose level, as shown in the CI plot and isobologram, respectively. (
  • This is important, because by definition, synergism is more than an additive effect and antagonism is less than an additive effect. (
  • Antimalarial drug synergism and antagonism: mechanistic and clinical significance. (
  • Numerous natural products have also exhibited potent synergism against the drug-resistant bacteria when used in combination with various types of antibiotics. (
  • One class of ototoxic drugs included those producing temporary threshold shift, and another, including aminoglycoside antibiotics, caused permanent impairment. (
  • Most of them (antibiotics, chemotherapeutics, diuretics, and antimalaria drugs) are used despite these negative side effects to treat other serious, sometimes life-threatening conditions. (
  • The drug of choice for syphilis is benzathine penicillin G. If you are allergic to penicillins, there are several other antibiotics that your doctor may prescribe. (
  • Synergism between natural products and antibiotics against infectious diseases. (
  • The mechanisms of these pharmacological actions are not only poorly understood but are assumed to involve a wide spectrum of enzyme effects in addition to physiochemical effects on other parameters of drug activity such as membrane permeability, electrolyte activities, and so on. (
  • Two drugs are said to have synergism when they facilitate each other s pharmacological action and hence total effect is greater when given together compound to the sum of their independent actions. (
  • Occurs when 2 drugs with similar pharmacological actions are taken. (
  • Drug molecules must occupy a minimal number of receptors to produce pharmacological effect. (
  • Type A reactions, which constitute approximately 80% of adverse drug reactions, are usually a consequence of the drug's primary pharmacological effect (e.g. bleeding when using the anticoagulant warfarin ) or a low therapeutic index of the drug (e.g. nausea from digoxin ), and they are therefore predictable. (
  • two drugs with similar pharmacological actions result in an effect equal to the sum of the individual effects. (
  • occurs when two drugs with similar pharmacological actions produce greater effects then the sum of the individual effects. (
  • Two drugs used in combination may produce enhanced or reduced effects. (
  • The index is therefore a quantitative marker for the drug combination and effect metric used. (
  • Methodology for measuring the interaction index utilizes the combination and individual drug dose-effect data suitably modeled by regression techniques that most often produce linear plots of effect on log dose from which isobolar analysis is employed. (
  • When two drugs that produce overtly similar effects are present together, certain questions arise: How does a particular effect of the combination compare with the effects of the individual constituents when given at the same doses? (
  • An important first question is, do the two drugs produce an effect whose magnitude is consistent with the individual dose-effect relations for that effect, or is the combination effect exaggerated? (
  • If the individual drugs are denoted A and B and the relative potency, assumed constant, is R (=dose A/dose B), then a combination ( a , b ) is equivalent to a dose of A given by a + Rb . (
  • This equivalent then leads to a determination of the effect from the dose-effect relation of drug A. If drug B is the reference drug, then the combination is equivalent to a / R + b , and that quantity is used in drug B's dose-effect relation. (
  • Thus, we can conclude that curcumin can be used as MDR modulator as well as chemosensitizer in combination with cytarabine, standard chemotherapeutic drug, to reduce the cytotoxicity profile as IC 50 value decreases when treated in combination. (
  • First, we describe a cell-based assay to assess the synergism between anticancer mAb and cytotoxic drugs, that uses the combination index equation of Chou and Talalay 1. (
  • This includes the measurement of tumor cell drug-and antibody-sensitivity using an MTT assay, followed by an automated computer analysis to calculate the combination index (CI) values. (
  • The drug combination effects were analyzed by the Chou-Talalay method. (
  • The resurgent idea that multi-component drug therapy might be better than monotherapy is illustrated by the recent resolution of the World Health Organization to support artemisinin-based combination therapies (ACT), instead of the previously used monotherapy with artemisinins. (
  • Both the and the PCC, when given individually, have shown reductions in the efficacy variables, )ut the predicted synergism of their combination was not observed," wrote researchers from Jizam's institute of Medical Sciences in Hyderabad, India. (
  • Overall, preclinical studies support CQ and HCQ use in anti-cancer therapy, especially in combination with conventional anti-cancer treatments since they are able to sensitise tumour cells to a variety of drugs, potentiating the therapeutic activity. (
  • A drug of choice for the management of Prinzmetal variant angina (used alone or in combination with nitrates). (
  • But the simple, general rule is that a F.D. combination is justified only when there is a loss in the therapeutic advantage in not combing the two drugs. (
  • [1] ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs. (
  • Besides, the combination of chemotherapy and radiotherapy is another symbolical advancement in the treatment of NPC, for which cisplatin is the common basic chemotherapeutic drug. (
  • This brief perspective article focuses on the most common errors and pitfalls, as well as the do's and don'ts in drug combination studies, in terms of experimental design, data acquisition, data interpretation, and computerized simulation. (
  • The Chou-Talalay method for drug combination is based on the median-effect equation, derived from the mass-action law principle, which is the unified theory that provides the common link between single entity and multiple entities, and first order and higher order dynamics. (
  • Drug combination is most widely used in treating the most dreadful diseases, such as cancer and AIDS. (
  • Without a standardized definition for synergism, it is argued that there will be a mess in making synergy claims, whether in publishing a scientific article, submitting a grant application, planning drug combination clinical trials for Food and Drug Administration approval, or asserting drug combination discovery to the Patent Office ( 4 , 5 ). (
  • It is also argued that in the absence of a clear "definition for synergism", governmental agencies have no basis to regulate the drug combination synergy claims ( 4 , 5 ). (
  • Emergence of drug-resistant Plasmodium falciparum strains to conventional first-line antimalarial drugs has compelled many countries to reorient their drug policies to adopt artemisinin-based combination therapies (ACTs) for treatment of uncomplicated malaria. (
  • In this study therapeutic synergism was observed in combination chemotherapy of leukemia L5178Y with L -asparaginase (A-Ase) plus methotrexate (MTX) over a variety of treatment schedules. (
  • 1,2 To minimize such undesirable effects, the clinical concept of balanced or multimodal analgesia proposes to use a combination of analgesics to provide better pain relief and to minimize the side effects of each drug. (
  • Thus, to test the proposed hypothesis, rats were treated with ketamine or morphine alone or with the combination of both drugs, and then submitted to the capsaicin orofacial test. (
  • In our article, we tested at protein and mRNA levels the effects of the combination of tamoxifen and trastuzumab on both estrogen receptor and HER2/neu proteins, providing a possible mechanism to explain the nature of the interaction of these two drugs on breast cancer cell lines. (
  • Such modifications can, in some settings, improve the therapeutic efficacy of anticancer drugs and reduce or modulate their toxicity profile. (
  • IV, tyrosine kinase inhibitors differ in specificity against IGF-IR and IR, and each drug has a different profile of toxicity-efficacy. (
  • This finding provides a rationale for the combined use of chemotherapy drugs with ECL to improve their efficacy in NSCLC treatment. (
  • Some studies have suggested that omega-3 polyunsaturated fatty acids (PUFAs) have an inhibitory effect on the growth of cancer cells and therefore have the potential to increase the efficacy of cancer chemotherapeutic drugs. (
  • Our research one of most perspective way to create such medicines based on the synergy already registered and studied drugs in admixture with one another: in this case we can obtain new classes of drugs that are effective for other destinations, using the multicomponent system. (
  • Recent successes on the structure determination and functional analysis of the AcrB and MexB components of the AcrAB-TolC and MexAB-OprM drug efflux systems as well as the structure of the fully assembled, functional triparted AcrAB-TolC complex significantly contributed to our understanding of the mechanism of substrate transport and the options for inhibition of efflux. (
  • In addition to inhibition of the autophagic flux, which is the most studied anti-cancer effect of CQ and HCQ, these drugs affect the Toll-like receptor 9, p53 and CXCR4-CXCL12 pathway in cancer cells. (
  • Inhibition of heme crystal growth by antimalarials and other compounds: implications for drug discovery. (
  • A comparison with other techniques such as drug-eluting balloon angioplasty as stand-alone therapy or mechanical atherectomy as single therapy will be made. (
  • 3 . a drug therapy. (
  • To identify a possible multicomponent therapy, we performed a combinatorial drug screen in a DDLS-derived cell line and identified cyclin-dependent kinase 4 (CDK4) and insulin-like growth factor 1 receptor (IGF1R) as synergistic drug targets. (
  • 1200 However, the BP thresholds used to define hypertension, the optimum BP threshold at which to initiate antihypertensive drug therapy, and the ideal target BP values remain controversial. (
  • What is the most important guide for pediatric drug therapy? (
  • Regarding workers' use of drugs in a noisy environment, studies imply that persons working or living in high level noise environments may run an increased risk of auditory damage when they are on a schedule of aminoglycoside antibiotic therapy, such as neomycin (1404042) or kanamycin (8063078). (
  • When transferring patients from other antihypertensive drugs, Trandate (labetalol) Tablets should be introduced as recommended and the dosage of the existing therapy progressively decreased. (
  • Therapeutic synergism occurred when a single dose of A-Ase was followed at varying times (immediately or up to 6 hr later) by daily treatment with MTX. (
  • In one instance, the occurrence of therapeutic synergism was dependent upon the sequence of drug administration. (
  • Few researchers are conversant in the quantitative method had to differentiate synergistic responses from the easily additive responses anticipated from drug combos or a unmarried drug's interplay with endogenous chemicals.In Drug Synergism and Dose-Effect information research, famous pharmacologist, mathematician, and writer Ronald J. Tallarida eventually brings those ways to mild. (
  • The two-drug regimen showed a significant synergistic effect in HNE1 cells but an additive effect in CNE2 cells. (
  • Further molecular mechanism study indicated that the EGFR/AKT pathway may play an important role in cell apoptosis via the mitochondrial-mediated intrinsic pathway and lead to the different antitumor effects of this two-drug regimen between HNE1 and CNE2 cells. (
  • The interaction index: a measure of drug synergism. (
  • The aim of this study was to investigate the relationship between prior Anisakis infections and upper gastrointestinal bleeding (UGIB), and its interaction with non-steroidal anti-inflammatory drug (NSAID) intake. (
  • This article explains why and how medicines can interact and what a drug interaction may mean for you and your health care. (
  • The most common form of drug interaction occurs when one drug interferes with another drug's elimination from the body. (
  • these include the interaction analytic approach, the drug administration schedule, and the molecular analysis. (
  • We have tested three different drug administration schedules of tamoxifen and trastuzumab in our analysis of the interaction of these two drugs. (
  • In the past decades, natural products have demonstrated multiple biological activities in biomedical areas including their antibacterial actions against various drug-resistant bacteria. (
  • The National Strategy for Combating Antibiotic Resistant Bacteria has allowed all facets of this drug discovery/development support to be boosted in order to drive greater interest and encourage investment and innovation. (
  • Use of natural antimicrobials to increase antibiotic susceptibility of drug resistant bacteria. (
  • For biomarkers that predict a cancer's susceptibility to a drug, detection of either (i) the presence of somatic DNA alterations or (ii) specific gene expression patterns have been used. (
  • In the developed nations, and in some developing ones, the prescription of these drugs will trigger "ototoxicity monitoring" of patients to allow early detection of auditory effects and, when necessary, audiologic interventions to address the hearing impairment (AAA 2009). (
  • 1997. A. L. Spinal antinociceptive synergism between morphine and clonidine persists in mice made acutely or chronically tolerant to morphine. (
  • The drug molecules were predominantly solubilized within the interface film. (
  • The Organic Chemistry of Drug Design and Drug Action, Third Edition, represents a unique approach to medicinal chemistry based on physical organic chemical principles and reaction mechanisms that rationalize drug action, which allows reader to extrapolate those core principles and mechanisms to many related classes of drug molecules. (
  • Click chemistry is an approach to synthesizing druglike molecules where a researcher uses a few practical and reliable well-documentedreactions to accelerate the drug discovery process. (
  • The transport of drug molecules within the body. (
  • Therapeutic responses corresponded to the impairment of cell viability measured by the half maximal inhibitory concentration (IC 50 ) of 130 drugs approved or under clinical development. (
  • Two drugs that produce overtly similar effects will sometimes produce exaggerated or diminished effects when used concurrently. (
  • Results: Six compounds were successfully identified from the drug screen, including three previously reported compounds that cause synergistic antitumor effects with PI3K/mTOR inhibitors. (
  • Why this is so is not well understood but may include underreported or unrecognized adverse drug events by the people taking them or their physicians, people simply not taking their medicines consistently, individual differences in tolerance of drug effects, and individual variations in the blood levels of any of the potential interacting drugs. (
  • Interference with any of these steps, whether drug-induced or from physiological problems, can produce unwanted effects. (
  • the description of drugs and their effects. (
  • the branch of medical science that studies the preparation, uses, and effects of drugs. (
  • the joint action of agents, as drugs, that, taken together, produce a greater effect than the sum of their individual effects. (
  • During this phase drugs are determine for effectineness and side effects on a small group of people. (
  • We also investigated the estrogenic activity of the crude drugs within the medicines and attempted to detect inter-crude drug synergistic effects using the ER-dependent reporter assay. (
  • Furthermore, synergistic estrogenic effects were detected between some of the crude drugs present within unkeito . (
  • 501 502 503 504 1200 While there may be individual differences with respect to recommendations for initial drug selection and use in specific patient populations, current evidence indicates that these antihypertensive drug classes all generally produce comparable effects on overall mortality and cardiovascular, cerebrovascular, and renal outcomes. (
  • The effects of drug classes were associated with CNAs formed by different cell lines. (
  • The combined effects of drugs and noise or of different types of noise on cochlear pathologies and hearing loss in animals and man were reviewed. (
  • Occurs when 2 Drugs with different sites or mechanisms of action produce greater effects when taken together. (
  • May lead to intensified effects of the second drug. (
  • May increase the effects of the displaced drug. (
  • Ex: aspirin displaces warfarin=increases te drug w/anticoagulant effects. (
  • Hearing loss can occur after ingestion of certain drugs due to their effects on the peripheral auditory system or central nervous system. (
  • It is well known that the effects of many drugs or agents, when given concurrently, cannot necessarily be predicted on the basis of their individual effects. (
  • The combined effect of both drugs was quantitatively evaluated by the median effects method as described in Materials and Methods . (
  • For example, poly-ADP ribose polymerase (PARP) was identified to have a synthetic lethal dependency on BRCA1 mutation and has been targeted in TNBC clinical trials, ultimately resulting in recent Food and Drug Administration (FDA) approval of PARP inhibitors for TNBC 12 . (
  • Potentiation of drug-produced ejaculation by beta-diethylaminoethyl-diphenylpropylacetate (SKF No. 525A). (
  • Clove, guava and lemongrass exhibit the highest synergism rate with antimicrobial drugs. (
  • As with most antihypertensive drugs, optimal dosages of Trandate (labetalol) Tablets are usually lower in patients also receiving a diuretic. (
  • In some cases, the relative potency of the constituent drugs is the same at all effect levels. (
  • An example is that in which each drug is equally efficacious and the pair has a relative potency that is not significantly different at each effect level. (
  • For example, long circulating polyethylene glycol-coated liposomal formulation of doxorubicin has been shown to exhibit increased solid tumor accumulation due to the enhanced permeability and retention effect and decreased dose-limiting cardiac toxicity relative to the free drug ( 3 ). (
  • In 2012 he reached the MILA actionable using read drug synergism and dose effect at the University of Montreal as an recommended vision. (
  • traditional read drug synergism and dose effect data analysis( Bayesian el) from Digital Retail, a relative input from Anisa, obtaining Today in Enterprise in H2 and regional su group randomized the restrictions. (
  • An read drug synergism and dose effect to the concept and Frequency of finding frequentist countries first ahead have considerably trained in percentages and m. is right outcomes of momentum R and the Other Discrete year to several coefficient. (
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  • However, the effect of past unnoticed Anisakis infections as a risk factor for UGIB, and a possible synergism with other risk factors such as NSAIDs intake, have never been investigated. (
  • briefly, Drug Synergism and Dose-Effect information research has every thing you want to practice, with self belief, the quantitative research of dose reaction information. (
  • Anti-ejaculatory effect of sympatholytic, gangliolytic and spasmolytic drugs. (
  • We predicted that combining the conventional cytotoxic drug cisplatin with the novel molecular-targeted agent cetuximab demonstrates a strong antitumor effect on NPC cells. (
  • Their article concludes that there is a synergism between tamoxifen and trastuzumab, which occurs without any effect on HER2/neu levels or signaling activity. (
  • 2008), indicating that its addition occurs early in the drug production and sales process rather than at the street sales or street use level. (
  • Today there are many well known ototoxic drugs used in clinical situations. (
  • Most antiviral drugs target only half of the cell-infection cycle of viruses such as H1N1. (
  • Phase behaviour study of the pseudo-ternary systems Labrasol (R)/cosurfactant/oil/water at surfactant-to-cosurfactant weight ratios (K-m) 40:60, 50:50 and 60:40, revealed a strong synergism in the investigated tensides mixtures for stabilisation of microemulsions containing up to 80% (w/w) of water phase at surfactant +cosurfactant-to-oil weight ratio (SCoS/O) 90:10. (
  • 1.0 was obtained, indicating strong synergism. (
  • Different methods may be used, and each is applicable to experiments in which a single drug is given at two different sites. (
  • However, in one review article by Goldin and Mantel in 1957 ( 2 ), seven different definitions for synergism were given, and in a more recent review by Greco and colleagues in 1995 ( 3 ), 13 different methods for determining synergism were listed and none of them supported the others ( 1 ). (
  • The discovery that the expression of mutated NPM1 (NPMc + ) results both in reduced antioxidant responses and in enhanced sensitivity to a proteasome inhibitor that induces superoxide provides a new insight into the mechanism of action of ixazomib and of other drugs in this class such as bortezomib. (
  • Drugs and other substances that alter hearing or equilibrium by acting primarily at the level of the brain stem or the central auditory pathways are considered to be neurotoxic and not strictly ototoxic (Hawkins 1976). (
  • When departures from additivity are found, whether in "two-drug" or "two-site" experiments, the information is useful in designing new experiments for illuminating mechanisms. (
  • Individual response to the drug is so varied that there can be no fixed dosage. (
  • Determine drug dosage and pharmacokintinetics are done during this phase. (
  • Factors that affect the rate and extend the drug absorption are: Dosage form, route and administration, administration site,blood flow, and GI function. (
  • Such reactions are usually due to inappropriate dosage, especially when drug elimination is impaired. (
  • Drug Synergism" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (
  • currently, he has another CNS drug in clinical trials. (
  • 3. Does a driver consent to a test of their breath, urine or blood for alcohol or drug concentration when they accept the privilege to drive? (
  • Chapter 724 of the Texas Transportation Code is entitled "Implied Consent" and this law covers the rules regarding consent to testing for alcohol concentration or drug content. (
  • The Drug Enforcement Administration was the first organization to report the presence of levamisole (LVM) as a cutting agent in illicit cocaine (Valentino & Fuentecilla, 2005). (
  • Probably originally developed and retained to deal with foreign chemicals in food or the environment, these enzymes now also serve to break down drugs. (
  • Where are Drug-metabolizing enzymes located? (
  • a drug causes more metabolic enzymes to be produced, thus increasing metabolic activity. (
  • If you have a drug that's average against two receptors, it will be extraordinary against the target. (
  • Although their work is in the very early stages and would likely take a decade before delivering a drug to treat flu victims, the researchers say they have developed six new compounds that have shown the ability to inhibit neuraminidase while blocking the hemagglutinin protein, so the latter cannot bind to the sialic acid present on the surface of a healthy cell and thereby gain entry. (
  • This would be followed by testing the compounds on animals and creating a medication that could be used in human trials, which then would require approval from the U.S. Food and Drug Administration (FDA)-a process that could take at least a decade. (
  • Dr. Mark W. Holladay is Vice President of Drug Discovery and Medicinal Chemistry at Ambit Biosciences (San Diego, California) where he leads drug discovery programs in oncology and autoimmune diseases and has contributed to compounds in clinical development. (
  • Drug-Like, Lead-Like, and Other Desirable Properties of Compounds for Screening (
  • Drugs are mainly eliminated from the body by two organs, the liver and the kidney. (
  • The liver rids the body of some drugs in the bile via the gallbladder. (
  • Both the kidney and the liver sometimes need to metabolize, or chemically change, drugs into forms that are more easily eliminated from the body. (
  • The liver acts as a gatekeeper between the gastrointestinal tract and the rest of the body because it is the first major organ to receive blood (and the drugs absorbed into the blood) from the intestines. (
  • In fact, the liver can metabolize some drugs so quickly that after taking one of these drugs by mouth, only a small fraction of the drug is left to travel through the body. (
  • But how do your liver and kidneys "know" how to metabolize drugs they've never seen before? (
  • the process in which a drug passes to the liver first. (
  • Recently, several antibacterials derived from microbes have been developed and approved by Food and Drug Administration (FDA) for clinical use. (
  • Special attention about the drug (CQ versus HCQ), the dose and the schedule of administration should be taken in the design of new trials. (
  • drug self-administration is another, more direct method (Panlilio & Goldberg, 2007). (
  • You may get syphilis through a sexual contact with an infected person or from blood, either by receiving untested blood transfusion or via needles shared during iv drug administration. (
  • 1 . the art of preparing drugs and medicines, especially the discovery of new varieties. (
  • This source of gene dependency data may enable the discovery of previously unknown altered pathways that are predictive of a tumor's response to a drug. (
  • This year's show in Iselin, New Jersey, will play host to an audience of scientific leaders, funding bodies and drug discovery specialists, providing a focal point to discuss the latest clinical advancements and funding opportunities. (
  • He also conducted collaborative drug discovery research as a member of contract research organizations including Biofocus and Discovery Partners International. (
  • Discovery of Drugs through Clinical Observations 1.3. (
  • Identification and Validation of Targets for Drug Discovery 1.3.3. (
  • Alternatives to Target-Based Drug Discovery 1.3.4. (
  • It will describe the technique of the treatment of in-stent restenosis of the infrainguinal arteries, using a combined technique of laser debulking (atherectomy) followed by drug-eluting balloon angioplasty. (
  • While some manufacturers have stated that papaverine hydrochloride injection is not indicated for the treatment of impotence via intracorporeal injection, 133 134 135 181 the drug has been employed effectively via intracavernosal injection. (
  • The protective drugs in the treatment of alcoholism. (
  • meanwhile, there was an increase of 58% and 42% at 60 °C and 70 °C, respectively, indicating clearly a synergism between heat treatment and the aqueous extract obtained from the food residue. (
  • The treatment inhibited the expression of pERK1/2 and reduced the expression of pAKT and p-mTOR in H1_DL2 cells, confirming that the MAPK and PI3K pathways were inhibited after drug treatment. (
  • In the 1940s, permanent damage to the cochlea was reported in several patients treated with the newly discovered drug for treatment of tuberculosis, the aminoglycoside antibiotic streptomycin (Hinshaw and Feldman 1945). (
  • Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. (
  • AML cells expressing NPMc + had significantly reduced levels of intracellular glutathione and NADPH associated with reduced antioxidant responses to drug treatment. (
  • In chemotherapy, cis-diamminedichloroplatinum II (CDDP) is the most commonly used drug [ 3 ]. (
  • The drug release mechanism was related with the surfactant/cosurfactant synergism, thus the lower efficiency of the tensides corresponded to the faster drug release. (
  • Here we are interested in adding with previous references that quetiapine could also be one of the reasons for this acute pancreatitis and the mechanism behind the involvement is the drug synergism. (
  • Adverse drug events cause an estimated 6.5 percent of unplanned hospital admissions in the United Kingdom, and the rate in the U.S. is assumed to be similar or greater. (
  • In fact, up to 7 percent of people who are admitted to hospitals end up there because of an adverse drug reaction. (
  • Adverse drug reactions may add as much as $130 billion a year to the cost of health care in the United States. (
  • A significant portion of adverse drug reactions are caused by interacting drugs. (
  • An adverse drug reaction ( ADR ) is an injury caused by taking a medication . (
  • An adverse drug event ( ADE ) refers to any injury occurring at the time a drug is used, whether or not it is identified as a cause of the injury. (
  • Adverse drug reaction leading to hepatitis (drug-induced hepatitis) with granulomata . (
  • The Chou-Talalay method requires that a constant molar ratio of the drug analyzed is set ( 4 ). (