Drug Combinations: Single preparations containing two or more active agents, for the purpose of their concurrent administration as a fixed dose mixture.Drug Synergism: The action of a drug in promoting or enhancing the effectiveness of another drug.Drug Therapy, Combination: Therapy with two or more separate preparations given for a combined effect.Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug.Antineoplastic Combined Chemotherapy Protocols: 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.Proguanil: A biguanide compound which metabolizes in the body to form cycloguanil, an anti-malaria agent.Methenamine: An anti-infective agent most commonly used in the treatment of urinary tract infections. Its anti-infective action derives from the slow release of formaldehyde by hydrolysis at acidic pH. (From Martindale, The Extra Pharmacopoeia, 30th ed, p173)Antimalarials: Agents used in the treatment of malaria. They are usually classified on the basis of their action against plasmodia at different stages in their life cycle in the human. (From AMA, Drug Evaluations Annual, 1992, p1585)Dapsone: A sulfone active against a wide range of bacteria but mainly employed for its actions against MYCOBACTERIUM LEPRAE. Its mechanism of action is probably similar to that of the SULFONAMIDES which involves inhibition of folic acid synthesis in susceptible organisms. It is also used with PYRIMETHAMINE in the treatment of malaria. (From Martindale, The Extra Pharmacopoeia, 30th ed, p157-8)Artemisinins: A group of SESQUITERPENES and their analogs that contain a peroxide group (PEROXIDES) within an oxepin ring (OXEPINS).Drug Therapy: The use of DRUGS to treat a DISEASE or its symptoms. One example is the use of ANTINEOPLASTIC AGENTS to treat CANCER.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.Atovaquone: A hydroxynaphthoquinone that has antimicrobial activity and is being used in antimalarial protocols.Cell Line, Tumor: A cell line derived from cultured tumor cells.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Drug Screening Assays, Antitumor: Methods of investigating the effectiveness of anticancer cytotoxic drugs and biologic inhibitors. These include in vitro cell-kill models and cytostatic dye exclusion tests as well as in vivo measurement of tumor growth parameters in laboratory animals.Methylthioinosine: 6-(Methylthio)-9-beta-D-ribofuranosylpurine. An analog of inosine with a methylthio group replacing the hydroxyl group in the 6-position.Cyclopentolate: A parasympatholytic anticholinergic used solely to obtain mydriasis or cycloplegia.Drug Antagonism: 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.Tropicamide: One of the MUSCARINIC ANTAGONISTS with pharmacologic action similar to ATROPINE and used mainly as an ophthalmic parasympatholytic or mydriatic.Cellophane: A generic name for film produced from wood pulp by the viscose process. It is a thin, transparent sheeting of regenerated cellulose, moisture-proof and sometimes dyed, and used chiefly as food wrapping or as bags for dialysis. (Grant & Hackh's Chemical Dictionary, 5th ed & McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Sulfamethoxazole: 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)Pyrimethamine: One of the FOLIC ACID ANTAGONISTS that is used as an antimalarial or with a sulfonamide to treat toxoplasmosis.Mefloquine: A phospholipid-interacting antimalarial drug (ANTIMALARIALS). It is very effective against PLASMODIUM FALCIPARUM with very few side effects.Drug Resistance: Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration.Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form.Inhibitory Concentration 50: The concentration of a compound needed to reduce population growth of organisms, including eukaryotic cells, by 50% in vitro. Though often expressed to denote in vitro antibacterial activity, it is also used as a benchmark for cytotoxicity to eukaryotic cells in culture.Drug Evaluation, Preclinical: Preclinical testing of drugs in experimental animals or in vitro for their biological and toxic effects and potential clinical applications.Floxuridine: An antineoplastic antimetabolite that is metabolized to fluorouracil when administered by rapid injection; when administered by slow, continuous, intra-arterial infusion, it is converted to floxuridine monophosphate. It has been used to treat hepatic metastases of gastrointestinal adenocarcinomas and for palliation in malignant neoplasms of the liver and gastrointestinal tract.Sulfadoxine: A long acting sulfonamide that is used, usually in combination with other drugs, for respiratory, urinary tract, and malarial infections.Cisplatin: 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.PyrazinesMolecular Targeted Therapy: Treatments with drugs which interact with or block synthesis of specific cellular components characteristic of the individual's disease in order to stop or interrupt the specific biochemical dysfunction involved in progression of the disease.Rifampin: A semisynthetic antibiotic produced from Streptomyces mediterranei. It has a broad antibacterial spectrum, including activity against several forms of Mycobacterium. In susceptible organisms it inhibits DNA-dependent RNA polymerase activity by forming a stable complex with the enzyme. It thus suppresses the initiation of RNA synthesis. Rifampin is bactericidal, and acts on both intracellular and extracellular organisms. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p1160)Nanoconjugates: Tailored macromolecules harboring covalently-bound biologically active modules that target specific tissues and cells. The active modules or functional groups can include drugs, prodrugs, antibodies, and oligonucleotides, which can act synergistically and be multitargeting.Microbial Sensitivity Tests: Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses).Amodiaquine: A 4-aminoquinoline compound with anti-inflammatory properties.Xenograft Model Antitumor Assays: In vivo methods of screening investigative anticancer drugs, biologic response modifiers or radiotherapies. Human tumor tissue or cells are transplanted into mice or rats followed by tumor treatment regimens. A variety of outcomes are monitored to assess antitumor effectiveness.Cell Survival: 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.Amikacin: A broad-spectrum antibiotic derived from KANAMYCIN. It is reno- and oto-toxic like the other aminoglycoside antibiotics.Chloroquine: The prototypical antimalarial agent with a mechanism that is not well understood. It has also been used to treat rheumatoid arthritis, systemic lupus erythematosus, and in the systemic therapy of amebic liver abscesses.Phentermine: A central nervous system stimulant and sympathomimetic with actions and uses similar to those of DEXTROAMPHETAMINE. It has been used most frequently in the treatment of obesity.Fluorouracil: A pyrimidine analog that is an antineoplastic antimetabolite. It interferes with DNA synthesis by blocking the THYMIDYLATE SYNTHETASE conversion of deoxyuridylic acid to thymidylic acid.SesquiterpenesBoronic Acids: Inorganic or organic compounds that contain the basic structure RB(OH)2.Doxorubicin: Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.Naphthoquinones: Naphthalene rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups.Antifungal Agents: 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.Apoptosis: 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.Fluorenes: A family of diphenylenemethane derivatives.Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.DeoxycytidinePiperazinesTreatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series.Drug-Related Side Effects and Adverse Reactions: Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.Niacinamide: An important compound functioning as a component of the coenzyme NAD. Its primary significance is in the prevention and/or cure of blacktongue and PELLAGRA. Most animals cannot manufacture this compound in amounts sufficient to prevent nutritional deficiency and it therefore must be supplemented through dietary intake.Drug Resistance, Neoplasm: Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.Antitubercular Agents: Drugs used in the treatment of tuberculosis. They are divided into two main classes: "first-line" agents, those with the greatest efficacy and acceptable degrees of toxicity used successfully in the great majority of cases; and "second-line" drugs used in drug-resistant cases or those in which some other patient-related condition has compromised the effectiveness of primary therapy.Plasmodium falciparum: A species of protozoa that is the causal agent of falciparum malaria (MALARIA, FALCIPARUM). It is most prevalent in the tropics and subtropics.Pharmacology: The study of the origin, nature, properties, and actions of drugs and their effects on living organisms.Drug Administration Schedule: Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience.Trimethoprim: A pyrimidine inhibitor of dihydrofolate reductase, it is an antibacterial related to PYRIMETHAMINE. It is potentiated by SULFONAMIDES and the TRIMETHOPRIM, SULFAMETHOXAZOLE DRUG COMBINATION is the form most often used. It is sometimes used alone as an antimalarial. TRIMETHOPRIM RESISTANCE has been reported.Drug Design: The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis.Systems Biology: Comprehensive, methodical analysis of complex biological systems by monitoring responses to perturbations of biological processes. Large scale, computerized collection and analysis of the data are used to develop and test models of biological systems.Neoplasms: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.Amphotericin B: Macrolide antifungal antibiotic produced by Streptomyces nodosus obtained from soil of the Orinoco river region of Venezuela.Anti-HIV Agents: Agents used to treat AIDS and/or stop the spread of the HIV infection. These do not include drugs used to treat symptoms or opportunistic infections associated with AIDS.Parasitic Sensitivity Tests: Tests that demonstrate the relative effectiveness of chemotherapeutic agents against specific parasites.Vincristine: An antitumor alkaloid isolated from VINCA ROSEA. (Merck, 11th ed.)Phenylurea Compounds: Compounds that include the amino-N-phenylamide structure.Cytarabine: A pyrimidine nucleoside analog that is used mainly in the treatment of leukemia, especially acute non-lymphoblastic leukemia. Cytarabine is an antimetabolite antineoplastic agent that inhibits the synthesis of DNA. Its actions are specific for the S phase of the cell cycle. It also has antiviral and immunosuppressant properties. (From Martindale, The Extra Pharmacopoeia, 30th ed, p472)QuinolinesMalaria, Falciparum: Malaria caused by PLASMODIUM FALCIPARUM. This is the severest form of malaria and is associated with the highest levels of parasites in the blood. This disease is characterized by irregularly recurring febrile paroxysms that in extreme cases occur with acute cerebral, renal, or gastrointestinal manifestations.Anti-Bacterial Agents: Substances that reduce the growth or reproduction of BACTERIA.Medetomidine: An agonist of RECEPTORS, ADRENERGIC ALPHA-2 that is used in veterinary medicine for its analgesic and sedative properties. It is the racemate of DEXMEDETOMIDINE.QuinazolinesDrug Resistance, Multiple: Simultaneous resistance to several structurally and functionally distinct drugs.Paclitaxel: A cyclodecane isolated from the bark of the Pacific yew tree, TAXUS BREVIFOLIA. It stabilizes MICROTUBULES in their polymerized form leading to cell death.Clinical Trials, Phase I as Topic: Works about studies performed to evaluate the safety of diagnostic, therapeutic, or prophylactic drugs, devices, or techniques in healthy subjects and to determine the safe dosage range (if appropriate). These tests also are used to determine pharmacologic and pharmacokinetic properties (toxicity, metabolism, absorption, elimination, and preferred route of administration). They involve a small number of persons and usually last about 1 year. This concept includes phase I studies conducted both in the U.S. and in other countries.NitroimidazolesAntiprotozoal Agents: Substances that are destructive to protozoans.Drug Discovery: The process of finding chemicals for potential therapeutic use.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Benzenesulfonates: Organic salts and esters of benzenesulfonic acid.Antihypertensive Agents: Drugs used in the treatment of acute or chronic vascular HYPERTENSION regardless of pharmacological mechanism. Among the antihypertensive agents are DIURETICS; (especially DIURETICS, THIAZIDE); ADRENERGIC BETA-ANTAGONISTS; ADRENERGIC ALPHA-ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; CALCIUM CHANNEL BLOCKERS; GANGLIONIC BLOCKERS; and VASODILATOR AGENTS.Clinical Trials as Topic: Works about pre-planned studies of the safety, efficacy, or optimum dosage schedule (if appropriate) of one or more diagnostic, therapeutic, or prophylactic drugs, devices, or techniques selected according to predetermined criteria of eligibility and observed for predefined evidence of favorable and unfavorable effects. This concept includes clinical trials conducted both in the U.S. and in other countries.Pyrazinamide: A pyrazine that is used therapeutically as an antitubercular agent.Mice, SCID: Mice homozygous for the mutant autosomal recessive gene "scid" which is located on the centromeric end of chromosome 16. These mice lack mature, functional lymphocytes and are thus highly susceptible to lethal opportunistic infections if not chronically treated with antibiotics. The lack of B- and T-cell immunity resembles severe combined immunodeficiency (SCID) syndrome in human infants. SCID mice are useful as animal models since they are receptive to implantation of a human immune system producing SCID-human (SCID-hu) hematochimeric mice.Hydroxamic Acids: A class of weak acids with the general formula R-CONHOH.Antimetabolites, Antineoplastic: Antimetabolites that are useful in cancer chemotherapy.Itraconazole: A triazole antifungal agent that inhibits cytochrome P-450-dependent enzymes required for ERGOSTEROL synthesis.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Triazines: Heterocyclic rings containing three nitrogen atoms, commonly in 1,2,4 or 1,3,5 or 2,4,6 formats. Some are used as HERBICIDES.Mice, Nude: Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses.Taxoids: A group of diterpenoid CYCLODECANES named for the taxanes that were discovered in the TAXUS tree. The action on MICROTUBULES has made some of them useful as ANTINEOPLASTIC AGENTS.Methotrexate: An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of TETRAHYDROFOLATE DEHYDROGENASE and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA.Etoposide: A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle.Sirolimus: A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to IMMUNOPHILINS. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Ethambutol: An antitubercular agent that inhibits the transfer of mycolic acids into the cell wall of the tubercle bacillus. It may also inhibit the synthesis of spermidine in mycobacteria. The action is usually bactericidal, and the drug can penetrate human cell membranes to exert its lethal effect. (From Smith and Reynard, Textbook of Pharmacology, 1992, p863)Leukemia L1210Tumor Cells, Cultured: 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.Malaria: A protozoan disease caused in humans by four species of the PLASMODIUM genus: PLASMODIUM FALCIPARUM; PLASMODIUM VIVAX; PLASMODIUM OVALE; and PLASMODIUM MALARIAE; and transmitted by the bite of an infected female mosquito of the genus ANOPHELES. Malaria is endemic in parts of Asia, Africa, Central and South America, Oceania, and certain Caribbean islands. It is characterized by extreme exhaustion associated with paroxysms of high FEVER; SWEATING; shaking CHILLS; and ANEMIA. Malaria in ANIMALS is caused by other species of plasmodia.Pyridines: Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.Cell Cycle: The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.Drug Evaluation: Any process by which toxicity, metabolism, absorption, elimination, preferred route of administration, safe dosage range, etc., for a drug or group of drugs is determined through clinical assessment in humans or veterinary animals.Piperidines: A family of hexahydropyridines.Echinocandins: Cyclic hexapeptides of proline-ornithine-threonine-proline-threonine-serine. The cyclization with a single non-peptide bond can lead them to be incorrectly called DEPSIPEPTIDES, but the echinocandins lack ester links. Antifungal activity is via inhibition of 1,3-beta-glucan synthase production of BETA-GLUCANS.Benzoquinones: Benzene rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups.Cyclophosphamide: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the LIVER to form the active aldophosphamide. It has been used in the treatment of LYMPHOMA and LEUKEMIA. Its side effect, ALOPECIA, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer.Ketamine: A cyclohexanone derivative used for induction of anesthesia. Its mechanism of action is not well understood, but ketamine can block NMDA receptors (RECEPTORS, N-METHYL-D-ASPARTATE) and may interact with sigma receptors.Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task.Signal Transduction: 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.Antineoplastic Agents, Alkylating: A class of drugs that differs from other alkylating agents used clinically in that they are monofunctional and thus unable to cross-link cellular macromolecules. Among their common properties are a requirement for metabolic activation to intermediates with antitumor efficacy and the presence in their chemical structures of N-methyl groups, that after metabolism, can covalently modify cellular DNA. The precise mechanisms by which each of these drugs acts to kill tumor cells are not completely understood. (From AMA, Drug Evaluations Annual, 1994, p2026)Reverse Transcriptase Inhibitors: Inhibitors of reverse transcriptase (RNA-DIRECTED DNA POLYMERASE), an enzyme that synthesizes DNA on an RNA template.Protein Kinase Inhibitors: Agents that inhibit PROTEIN KINASES.TriazolesDacarbazine: An antineoplastic agent. It has significant activity against melanomas. (from Martindale, The Extra Pharmacopoeia, 31st ed, p564)Carboplatin: An organoplatinum compound that possesses antineoplastic activity.Models, Statistical: Statistical formulations or analyses which, when applied to data and found to fit the data, are then used to verify the assumptions and parameters used in the analysis. Examples of statistical models are the linear model, binomial model, polynomial model, two-parameter model, etc.Sulfonamides: A group of compounds that contain the structure SO2NH2.ThiazolesTacrolimus: A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro.Multiple Myeloma: A malignancy of mature PLASMA CELLS engaging in monoclonal immunoglobulin production. It is characterized by hyperglobulinemia, excess Bence-Jones proteins (free monoclonal IMMUNOGLOBULIN LIGHT CHAINS) in the urine, skeletal destruction, bone pain, and fractures. Other features include ANEMIA; HYPERCALCEMIA; and RENAL INSUFFICIENCY.HIV Infections: Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS).Drug Delivery Systems: Systems for the delivery of drugs to target sites of pharmacological actions. Technologies employed include those concerning drug preparation, route of administration, site targeting, metabolism, and toxicity.Antiviral Agents: Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Benzamides: BENZOIC ACID amides.Drug Resistance, Microbial: The ability of microorganisms, especially bacteria, to resist or to become tolerant to chemotherapeutic agents, antimicrobial agents, or antibiotics. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS).Drug Resistance, Viral: The ability of viruses to resist or to become tolerant to chemotherapeutic agents or antiviral agents. This resistance is acquired through gene mutation.Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories for solving biological problems including manipulation of models and datasets.Ethanolamines: AMINO ALCOHOLS containing the ETHANOLAMINE; (-NH2CH2CHOH) group and its derivatives.Benzimidazoles: Compounds with a BENZENE fused to IMIDAZOLES.Pyrroles: Azoles of one NITROGEN and two double bonds that have aromatic chemical properties.Fluconazole: Triazole antifungal agent that is used to treat oropharyngeal CANDIDIASIS and cryptococcal MENINGITIS in AIDS.Parasitemia: The presence of parasites (especially malarial parasites) in the blood. (Dorland, 27th ed)Adenine: A purine base and a fundamental unit of ADENINE NUCLEOTIDES.Histone Deacetylase Inhibitors: Compounds that inhibit HISTONE DEACETYLASES. This class of drugs may influence gene expression by increasing the level of acetylated HISTONES in specific CHROMATIN domains.Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.Breast Neoplasms: Tumors or cancer of the human BREAST.Camptothecin: An alkaloid isolated from the stem wood of the Chinese tree, Camptotheca acuminata. This compound selectively inhibits the nuclear enzyme DNA TOPOISOMERASES, TYPE I. Several semisynthetic analogs of camptothecin have demonstrated antitumor activity.GuanineCombined Modality Therapy: The treatment of a disease or condition by several different means simultaneously or sequentially. Chemoimmunotherapy, RADIOIMMUNOTHERAPY, chemoradiotherapy, cryochemotherapy, and SALVAGE THERAPY are seen most frequently, but their combinations with each other and surgery are also used.Indoles: Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.Models, Theoretical: Theoretical representations that simulate the behavior or activity of systems, processes, or phenomena. They include the use of mathematical equations, computers, and other electronic equipment.Treatment Failure: A measure of the quality of health care by assessment of unsuccessful results of management and procedures used in combating disease, in individual cases or series.Lung Neoplasms: Tumors or cancer of the LUNG.Analgesics: Compounds capable of relieving pain without the loss of CONSCIOUSNESS.Zidovudine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIV-induced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia.Proto-Oncogene Proteins c-bcl-2: Membrane proteins encoded by the BCL-2 GENES and serving as potent inhibitors of cell death by APOPTOSIS. The proteins are found on mitochondrial, microsomal, and NUCLEAR MEMBRANE sites within many cell types. Overexpression of bcl-2 proteins, due to a translocation of the gene, is associated with follicular lymphoma.Antineoplastic Agents, Phytogenic: Agents obtained from higher plants that have demonstrable cytostatic or antineoplastic activity.TOR Serine-Threonine Kinases: A serine threonine kinase that controls a wide range of growth-related cellular processes. The protein is referred to as the target of RAPAMYCIN due to the discovery that SIROLIMUS (commonly known as rapamycin) forms an inhibitory complex with TACROLIMUS BINDING PROTEIN 1A that blocks the action of its enzymatic activity.Ovarian Neoplasms: Tumors or cancer of the OVARY. These neoplasms can be benign or malignant. They are classified according to the tissue of origin, such as the surface EPITHELIUM, the stromal endocrine cells, and the totipotent GERM CELLS.Leukemia, Myeloid, Acute: Clonal expansion of myeloid blasts in bone marrow, blood, and other tissue. Myeloid leukemias develop from changes in cells that normally produce NEUTROPHILS; BASOPHILS; EOSINOPHILS; and MONOCYTES.HIV-1: The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte.Random Allocation: A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects.Vinblastine: Antitumor alkaloid isolated from Vinca rosea. (Merck, 11th ed.)Administration, Oral: The giving of drugs, chemicals, or other substances by mouth.Area Under Curve: A statistical means of summarizing information from a series of measurements on one individual. It is frequently used in clinical pharmacology where the AUC from serum levels can be interpreted as the total uptake of whatever has been administered. As a plot of the concentration of a drug against time, after a single dose of medicine, producing a standard shape curve, it is a means of comparing the bioavailability of the same drug made by different companies. (From Winslade, Dictionary of Clinical Research, 1992)Mice, Inbred BALB CGlioblastoma: A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures.Brain Neoplasms: Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain.Neoplasm Transplantation: Experimental transplantation of neoplasms in laboratory animals for research purposes.Receptor, Epidermal Growth Factor: A cell surface receptor involved in regulation of cell growth and differentiation. It is specific for EPIDERMAL GROWTH FACTOR and EGF-related peptides including TRANSFORMING GROWTH FACTOR ALPHA; AMPHIREGULIN; and HEPARIN-BINDING EGF-LIKE GROWTH FACTOR. The binding of ligand to the receptor causes activation of its intrinsic tyrosine kinase activity and rapid internalization of the receptor-ligand complex into the cell.Pancreatic Neoplasms: Tumors or cancer of the PANCREAS. Depending on the types of ISLET CELLS present in the tumors, various hormones can be secreted: GLUCAGON from PANCREATIC ALPHA CELLS; INSULIN from PANCREATIC BETA CELLS; and SOMATOSTATIN from the SOMATOSTATIN-SECRETING CELLS. Most are malignant except the insulin-producing tumors (INSULINOMA).Imidazoles: Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).Adrenergic beta-Antagonists: Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Antibodies, Monoclonal, Humanized: Antibodies from non-human species whose protein sequences have been modified to make them nearly identical with human antibodies. If the constant region and part of the variable region are replaced, they are called humanized. If only the constant region is modified they are called chimeric. INN names for humanized antibodies end in -zumab.Aspirin: The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. (From Martindale, The Extra Pharmacopoeia, 30th ed, p5)Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in ALCOHOLIC BEVERAGES.Angiotensin-Converting Enzyme Inhibitors: A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility.Immunosuppressive Agents: Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging.Survival Analysis: A class of statistical procedures for estimating the survival function (function of time, starting with a population 100% well at a given time and providing the percentage of the population still well at later times). The survival analysis is then used for making inferences about the effects of treatments, prognostic factors, exposures, and other covariates on the function.Dexamethasone: An anti-inflammatory 9-fluoro-glucocorticoid.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.DNA Damage: Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.Caspases: A family of intracellular CYSTEINE ENDOPEPTIDASES that play a role in regulating INFLAMMATION and APOPTOSIS. They specifically cleave peptides at a CYSTEINE amino acid that follows an ASPARTIC ACID residue. Caspases are activated by proteolytic cleavage of a precursor form to yield large and small subunits that form the enzyme. Since the cleavage site within precursors matches the specificity of caspases, sequential activation of precursors by activated caspases can occur.Receptor, erbB-2: A cell surface protein-tyrosine kinase receptor that is overexpressed in a variety of ADENOCARCINOMAS. It has extensive homology to and heterodimerizes with the EGF RECEPTOR, the ERBB-3 RECEPTOR, and the ERBB-4 RECEPTOR. Activation of the erbB-2 receptor occurs through heterodimer formation with a ligand-bound erbB receptor family member.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Infusions, Intravenous: The long-term (minutes to hours) administration of a fluid into the vein through venipuncture, either by letting the fluid flow by gravity or by pumping it.Hypertension: Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.Chromatography, High Pressure Liquid: Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.Behavior, Animal: The observable response an animal makes to any situation.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Recurrence: The return of a sign, symptom, or disease after a remission.Mutation: 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.Adenocarcinoma: A malignant epithelial tumor with a glandular organization.Proto-Oncogene Proteins c-akt: A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.Blood Pressure: PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS.Disease-Free Survival: Period after successful treatment in which there is no appearance of the symptoms or effects of the disease.Kidney: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.Cells, Cultured: 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.Kinetics: The rate dynamics in chemical or physical systems.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Survival Rate: The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods.Enzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.

Persistent damage to Enterocytozoon bieneusi, with persistent symptomatic relief, after combined furazolidone and albendazole in AIDS patients. (1/7446)

AIM: To investigate morphological changes in Enterocytozoon bieneusi and the duration of symptomatic relief after combination treatment with furazolidone and albendazole in AIDS patients. METHODS: Four severely immunocompromised AIDS patients with symptomatic E bieneusi infection of the gut received an 18 day course of combined furazolidone and albendazole (500 + 800 mg daily). All patients were monitored for parasite shedding in stool by light microscopy at the end of treatment and monthly during follow up. At the end of treatment, duodenal biopsy specimens obtained from three patients were studied by transmission electron microscopy by two pathologists blind to the patients' treatment or clinical outcome. Duodenal biopsy specimens obtained from one of the patients two months after completion of treatment were also studied electronmicroscopically. RESULTS: All patients had long lasting symptomatic relief, with a major decrease--or transient absence--of spore shedding in stools from completion of treatment. After treatment, changes in faecal spores were persistently found by light microscopy in all cases, and there was evidence of both a substantial decrease in the parasite load and ultrastructural damage in the parasite in all biopsy specimens. The treatment was well tolerated, and no patient had clinical or parasitological relapse during follow up (up to 15 months). CONCLUSIONS: The long lasting symptomatic relief observed in all four treated patients correlated with the persistent decrease in parasite load both in tissue and in stool, and with the morphological changes observed in the life cycle of the protozoan. These data suggest that combined treatment with furazolidone and albendazole is active against E bieneusi and may result in lasting remission even in severely immunocompromised patients.  (+info)

Emergent immunoregulatory properties of combined glucocorticoid and anti-glucocorticoid steroids in a model of tuberculosis. (2/7446)

In Balb/c mice with pulmonary tuberculosis, there is a switch from a protective Th1-dominated cytokine profile to a non-protective profile with a Th2 component. This switch occurs while the adrenals are undergoing marked hyperplasia. Treatment with the anti-glucocorticoid hormones dehydroepiandrosterone or 3 beta, 17 beta-androstenediol, during the period of adrenal hyperplasia, maintains Th1 dominance and is protective. We investigated the effects of these hormones as therapeutic agents by administering them from day 60, when the switch to the non-protective cytokine profile was already well established. Given at this time (day 60), doses that were protective when given early (from day 0) were rapidly fatal. A physiological dose of the glucocorticoid corticosterone was also rapidly fatal. However when the corticosterone and the anti-glucocorticoid (AED or DHEA) were co-administered, there was protection, with restoration of a Th1-dominated cytokine profile, enhanced DTH responses, and enhanced expression of IL-1 alpha and TNF alpha. Therefore this combination of steroids has an emergent property that is quite unlike that of either type of steroid given alone. It may be possible to exploit the ant-inflammatory properties of glucocorticoids while preserving a Th1 bias, by combining glucocorticoids with DHEA or suitable metabolites.  (+info)

Precocious estrus and reproductive ability induced by PG 600 in prepuberal gilts. (3/7446)

A total of 29 SPF Large White prepuberal gilts (mean age 152 days at treatment) were examined for estrous and ovulatory responses after PG 600 treatment. After treatment, 85.2% of the gilts showed standing estrus within 6 days. Whereas the treatment-to-estrus interval and duration were 3.7 and 1.9 days respectively. As ovulation occurred on Day 5 to 6, appropriate timing of artificial insemination would be about 4 days after treatment. Fertility of gilts revealed to be excellent, giving rise to a high percentage of normal embryos, 85.3%. Meanwhile, development and growth of fetuses were mostly normal. Other reproductive performances recorded were: mean litter size 6.8; mean birth weight 1.26 kg; weaning-to-return estrus interval 5 to 8 days. In conclusion, PG 600 was found to be useful in inducing fertile estrus in prepuberal gilts, a result which will be of interest for commercial pig farms.  (+info)

Granulocyte/macrophage colony-stimulating factor and interleukin-3 correct osteopetrosis in mice with osteopetrosis mutation. (4/7446)

Although young mice homozygous for the osteopetrosis (op) mutation usually developed prominent osteopetrosis, its severity was markedly reduced in aged op/op mice. This age-associated reversal of osteopetrosis was accompanied by the expansion of bone marrow cavities and increased numbers of tartrate-resistant acid phosphatase (TRAP)-positive cells and of macrophages in the bone marrow. The TRAP-positive cells were mononuclear and developed ruffled borders and numerous vesicles, vacuoles, and granules. Enzyme-linked immunosorbent assay demonstrated a significant elevation of serum granulocyte/ macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-3 levels in the aged op/op mice. To examine whether GM-CSF and/or IL-3 could correct osteopetrosis in young op/op mice, 5 ng of recombinant murine (rm)GM-CSF and/or 100 ng of rmIL-3 were injected daily into young op/op mice. In these treated young op/op mice, the bone marrow cavities were expanded significantly at 2 weeks after administration, associated with significantly increased numbers of TRAP-positive cells and bone marrow macrophages. TRAP-positive cells increased in number with days after injection. These results suggest that GM-CSF and IL-3 induce the development of osteoclasts to correct osteopetrosis in the op/op mice with aging.  (+info)

Transforming growth factor-alpha acting at the epidermal growth factor receptor reduces infarct volume after permanent middle cerebral artery occlusion in rats. (5/7446)

Transforming growth factor-alpha (TGF-alpha) is a ligand for the epidermal growth factor (EGF) receptor (EGFR), and is more abundant than EGF in the brain. The authors studied whether administration of exogenous TGF-alpha into the brain can protect neurons against ischemia in a model of permanent middle cerebral artery (MCA) occlusion in the rat, and whether any effect of TGF-alpha was mediated by EGFR by administering 4,5-dianilinophthalimide (DAPH), a protein-tyrosine kinase inhibitor with high selectivity for EGFR. Rats received either TGF-alpha (10 or 25 ng), DAPH (100 ng), DAPH plus TGF-alpha (25 ng), or vehicle in the ipsilateral first ventricle. Drugs were administered twice: 30 minutes before and 30 minutes after MCA occlusion, and infarct volume was evaluated 24 hours later. Transforming growth factor-alpha at the dose of 25 ng caused a statistically significant reduction of infarct volume (60%) in relation to ischemic rats administered vehicle. This reduction was no longer seen when TGF-alpha was administered in combination with DAPH. The present results show that TGF-alpha can protect neurons from ischemic damage, and that this effect is mediated by EGFR. It is suggested that activation of EGFR-mediated intracellular signalling pathways contributes to the survival of neural cells susceptible to ischemic injury.  (+info)

Spinal antinociceptive synergism between morphine and clonidine persists in mice made acutely or chronically tolerant to morphine. (6/7446)

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)

Persistent induction of apoptosis and suppression of mitosis as the basis for curative therapy with S-1, an oral 5-fluorouracil prodrug in a colorectal tumor model. (7/7446)

In an effort to improve the therapeutic selectivity of 5-fluorouracil (FUra) against colorectal cancer, S-1, a combination agent including a prodrug of FUra with two modulators, was recently developed by Taiho Pharmaceuticals Co. S-1 is a combination of tegafur (FT), 5-chloro-2,4-hydroxypyridine, and potassium oxonate in the molar ratio of 1.0:0.4:1.0, with the latter two components as inhibitors of dihydropyrimidine dehydrogenase and phosphoribosylpyrophosphate transferase, respectively. In this study, the therapeutic selectivity and efficacy of S-1 (oral) was compared with FT (oral) and FUra (i.v. infusion) in rats bearing advanced colorectal cancer by using clinically relevant schedules. The maximum tolerated doses (MTDs) of S-1, FT, and FUra were 31.5, 200, and 25 mg/kg/d for 7 days and 22.5, 150, and 12.5 mg/kg/d for 28 days, respectively. The therapeutic index of S-1 was 4- to 5-fold higher than that of either FT or FUra. S-1 achieved 100% complete tumor regression (CR) at its MTD in both 7-day and 28-day schedules. Furthermore, the high incidences of stomatitis, alopecia, and diarrhea observed with FUra and FT, were not observed with S-1. In an attempt to understand the basis for the observed superior therapeutic selectivity with S-1, we studied pharmacokinetic analysis of FUra, drug-induced apoptosis, suppression of mitosis, and inhibition of thymidylate synthase (TS) after S-1, FUra, or FT administration. The peak plasma FUra concentrations derived from FUra or S-1 (FT) at comparable MTDs were similar, but the plasma level of FUra was higher with S-1 than with FUra. Induction of high and sustained apoptosis was achieved with S-1. Although the initial level of apoptosis induced by FUra was comparable to S-1, it was not sustained. The sustained level of apoptosis appears to correlate with tumor growth inhibition. Mitotic figures were more greatly suppressed with S-1 treatment than with FUra. Studies on TS inhibition indicated that, although both S-1 and FUra caused a 4- to 6-fold induction of total TS protein, single oral administration of S-1 was superior to 24-h infusion of FUra in suppressing free TS. The data are consistent with the observation that the therapeutic efficacy of S-1 (100% cure) over FUra is associated with high and sustained levels of drug-induced apoptosis, greater suppression of mitosis, and inhibition of free TS in tumor tissues.  (+info)

Growth hormone-releasing peptide-2 infusion synchronizes growth hormone, thyrotrophin and prolactin release in prolonged critical illness. (8/7446)

OBJECTIVE: During prolonged critical illness, nocturnal pulsatile secretion of GH, TSH and prolactin (PRL) is uniformly reduced but remains responsive to the continuous infusion of GH secretagogues and TRH. Whether such (pertinent) secretagogues would synchronize pituitary secretion of GH, TSH and/or PRL is not known. DESIGN AND METHODS: We explored temporal coupling among GH, TSH and PRL release by calculating cross-correlation among GH, TSH and PRL serum concentration profiles in 86 time series obtained from prolonged critically ill patients by nocturnal blood sampling every 20 min for 9 h during 21-h infusions of either placebo (n=22), GHRH (1 microg/kg/h; n=10), GH-releasing peptide-2 (GHRP-2; 1 microg/kg/h; n=28), TRH (1 microg/kg/h; n=8) or combinations of these agonists (n=8). RESULTS: The normal synchrony among GH, TSH and PRL was absent during placebo delivery. Infusion of GHRP-2, but not GHRH or TRH, markedly synchronized serum profiles of GH, TSH and PRL (all P< or =0.007). After addition of GHRH and TRH to the infusion of GHRP-2, only the synchrony between GH and PRL was maintained (P=0.003 for GHRH + GHRP-2 and P=0.006 for TRH + GHRH + GHRP-2), and was more marked than with GHRP-2 infusion alone (P=0.0006 by ANOVA). CONCLUSIONS: The nocturnal GH, TSH and PRL secretory patterns during prolonged critical illness are herewith further characterized to include loss of synchrony among GH, TSH and PRL release. The synchronizing effect of an exogenous GHRP-2 drive, but not of GHRH or TRH, suggests that the presumed endogenous GHRP-like ligand may participate in the orchestration of coordinated anterior pituitary hormone release.  (+info)

  • The minimum inhibitory concentrations (MICs) and fractional inhibitory concentration (FIC) index was performed to assess the efficacy of the antibiotics alone and in combination. (news-medical.net)
  • They studied commercially available CAV (a duo of ceftazidime and avibactam) and compared its effectiveness to other first-line regimens using a screening tool endorsed by the FDA (called the hollow fiber system model, which allows for a quick examination of drug efficacy based on human lung pharmacokinetics). (eurekalert.org)
  • The efficacy and tolerability of Artesunate-Mefloquine fixed-dose combination (ASMQ FDC) was tested in children under 5 years of age with uncomplicated falciparum malaria. (medindia.net)
  • Nasdaq: CPXX), a biopharmaceutical company that is transforming the science of combination therapy and developing products to improve patient outcomes in cancer, announced their successful R&D efforts to apply the CombiPlex technology platform to optimize the efficacy of anticancer drug combinations incorporating molecularly targeted agents (MTAs). (thefreedictionary.com)
  • an agent patented by the company for its efficacy against cold viruses, and Xylometazoline - a well-known drug that targets inflamed nasal mucous membranes. (prlog.org)
  • We have observed excellent efficacy, the best reported to date, and very good tolerability, including limited peripheral neuropathy that has been problematic with other drug combinations. (uchospitals.edu)
  • The FDA generally requires only simple bioequivalence tests to ensure that drug dosing is consistent with the individual medicines, and, at most, a small human trial to prove similar efficacy. (nature.com)
  • In this study, we used image-based proliferation and apoptosis assays in colorectal cancer cell lines to systematically investigate the efficacy of combinations of two to six drugs that target critical oncogenic pathways. (aacrjournals.org)
  • Using the NCI ALMANAC, we identified several different drug combinations that have never before been tested together in humans but that nevertheless had powerful cell-killing effects in a number of the NCI-60 cell lines. (cancer.gov)
  • The inkjet technology dispenses uniform bacterial samples into each of the 96 wells in a standard lab testing plate to allow for rapid and consistent testing of different drug combinations. (bidmc.org)
  • The Radiotherapy-Drug Combinations Consortium (RaDCom) was established by CTRad and the Cancer Research UK (CRUK) Centre for Drug Development (CDD) in 2013. (ncri.org.uk)
  • ZURICH (Reuters) - An experimental drug from Roche helped people with an advanced form of skin cancer live longer without their disease worsening when used in combination with another treatment, the Swiss drugmaker said on Monday. (reuters.com)
  • Pharmaceutical companies are looking to combination therapy to yield better results and drug cocktails are expected to be crucial as oncologists seek to block cancer on multiple fronts. (reuters.com)
  • Roche is also investigating cobimetinib in combination with other experimental medicines, including an immunotherapy for the treatment of non-small cell lung cancer and colorectal cancer. (reuters.com)
  • A new drug combination may be effective in treating men with metastatic prostate cancer. (eurekalert.org)
  • The approach combines several drugs and attacks the cancer on several fronts," said Dr. Fred Saad, researcher at the University of Montreal Hospital Research Centre (CRCHUM) and principal investigator of the study. (eurekalert.org)
  • Dr. Fred Saad is principal investigator of the trial entitled "A Phase 3 Randomized, Placebo-controlled Double-blind Study of JNJ-56021927 in Combination with Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone in Subjects with Chemotherapy-naive Metastatic Castration-resistant Prostate Cancer (mCRPC) who did not Receive any Chemotherapy. (eurekalert.org)
  • Noncytotoxic biological agents act on specific molecular pathways to target cancer cells while sparing normal tissues, and therefore do not generally cause alopecia, vomiting, and myelosuppression that are characteristic of cytotoxic drugs. (hindawi.com)
  • NCI ALMANAC provides data showing how well pairs of FDA-approved cancer drugs kill tumor cells from the NCI-60 Human Tumor Cell Lines. (cancer.gov)
  • This resource, called the NCI ALMANAC , provides data showing how well pairs of Food and Drug Administration-approved cancer drugs performed in killing tumor cells from the NCI-60 Human Tumor Cell Lines , a library of cancer cell lines maintained by NCI. (cancer.gov)
  • So, when a novel compound is tested against cell lines in the NCI-60, it's possible to determine not just whether it kills the cells, but how it affects the molecular machinery of a cancer cell-information that is critical for understanding how a drug works. (cancer.gov)
  • The report from our NCI group in Cancer Research provides an ideal case report of what the NCI ALMANAC results might mean for advancing new drug combinations into human trials. (cancer.gov)
  • Data in the NCI ALMANAC showed that the combination of nilotinib and paclitaxel had robust cell-killing effects in blood cancer and triple-negative breast cancer cell lines. (cancer.gov)
  • A new study, led by Anthony Faber, Ph.D., member of the Developmental Therapeutics research program at VCU Massey Cancer Center, found that a novel epigenetic drug known as a H3K27me demethylase inhibitor can be used in combination with an existing drug called venetoclax to more effectively kill high-risk neuroblastoma cells. (medindia.net)
  • A new drug combination, which is effective against the skin cancer, could save millions of lives each year. (digitaljournal.com)
  • We discovered that this ribonuclease drug could be paired favorably with other cancer chemotherapeutic agents, and not only that, the pairing made logical sense in terms of the underlying biochemistry. (digitaljournal.com)
  • The study , conducted by professor Des Richardson of the Sydney Medical School, illustrate that drugs can control the spread and growth of cancer cells. (asbestos.com)
  • Chemotherapy is the use of drugs to kill cancer cells and shrink tumors. (lymphomainfo.net)
  • Many advances have been made (and are still underway) in chemotherapy over the years, and more and more drugs are becoming available to target specific kinds of cancer cells and to minimize side effects. (lymphomainfo.net)
  • The scientists agreed to emulate a combination trial model pioneered by the cancer field and use existing infrastructure for an initial trial of two amyloid-lowering agents. (alzforum.org)
  • The growth of the Global Drug-device Combination Products Market is driven by rise in incidence of chronic diseases such as diabetes, cancer, and respiratory problems, increase in casualties owing to accidents and trauma, rise in geriatric population, growth in home-based healthcare market, and technological advancements such as development of prefilled syringes. (openpr.com)
  • The drug combination delivers a double whammy to the way the KRAS gene makes cancer cells grow. (cancerresearchuk.org)
  • Lead author, Dr Udai Banerji, Cancer Research UK Reader at the Institute of Cancer Research, said: "There aren't yet any drugs to treat cancers with the KRAS mutation, so our study has given us a direction to focus future research on. (cancerresearchuk.org)
  • The drug AZD2014 is experimental and still in clinical trials to treat solid tumours (all cancer types except leukaemia, lymphoma or myeloma). (cancerresearchuk.org)
  • This study will test the safety and effectiveness of hydroxyurea, an anti-cancer drug, given together with the anti-HIV drugs didanosine, stavudine and efavirenz for treating children infected with human immunodeficiency virus (HIV). (clinicaltrials.gov)
  • The two drugs are frequently used alone to treat breast cancer. (orlandosentinel.com)
  • This new approval covers the use of gemcitabine (Gemzar) in combination with carboplatin to treat women who've suffered an ovarian cancer relapse at least 6 months after initial treatment. (cancernetwork.com)
  • With our platform, you can profile your compounds as single agents or combinations across hundreds of well-annotated cancer cell lines, and gain actionable insights in a short period of time. (horizondiscovery.com)
  • It's our belief that by combining conventional chemotherapy with MI-773, a drug that kills more cancer stem cells, we can have a more effective surgery or ablation. (eurekalert.org)
  • Vorinostat also sensitized PARPis insensitive cancer cell lines to 6-thioguanine (6-TG)-a drug that targets PARPis sensitive cells. (plos.org)
  • The challenge is to select which of the many drug combination possibilities and administration schedules are most suitable for clinical development across distinct cancer patient populations. (frontiersin.org)
  • Progression-free survival, the length of time that a patient doesn't experience any cancer growth, was significantly improved in the women who received the new drug combination compared to those who received a standard treatment. (mskcc.org)
  • To minimize the non-specific toxicity of drug combination during cancer therapy, we prepared a new system synthesized from bacteria to deliver the anticancer drugs cytosine arabinoside (Ara-C) and daunorubicin (DNR). (mdpi.com)
  • Scientists discovered that when breast cancer drug palbociclib was combined with lung cancer drug crizotinib, the two-drug combination was significantly more effective against cancer cells in the laboratory than either drug used on its own. (lancashiretelegraph.co.uk)
  • We still need to do more work to understand the full potential of combination treatment to increase the effectiveness of these drugs, but the approach looks highly promising and has the potential to be effective against several cancer types. (lancashiretelegraph.co.uk)
  • Our results illustrate how high-order drug combinations are needed to kill drug-resistant cancer cells, and they also show how systematic drug combination screening together with a molecular understanding of drug responses may help define optimal cocktails to overcome aggressive cancers. (aacrjournals.org)
  • During the acute and subacute phases of shoulder impingement syndrome, it is appropriate to use a short course of nonsteroidal anti-inflammatory drugs (NSAIDs) for analgesic and anti-inflammatory effects as an adjunct to the therapy program and other treatment modalities. (medscape.com)
  • NSAIDs are the most widely used drugs in the world, exhibiting anti-inflammatory, antipyretic, and analgesic activities. (medscape.com)
  • A combination drug is a fixed-dose combination (FDC) that includes two or more active pharmaceutical ingredients (APIs) combined in a single dosage form, which is manufactured and distributed in fixed doses. (wikipedia.org)
  • The synergy score S = ln f X ln f Y Σ doses max(0, Z data ) ( Z data − Z model ) sums up the excess inhibition over the HSA model with weights to account for drug dilution factors f X , f Y , and favor synergy at high inhibition levels. (nih.gov)
  • And each drug in each pair was tested at different doses, producing nearly 3 million data points. (cancer.gov)
  • 2) In a factorial study comparing A+B to A and to B, at the highest doses planned for the fixed combination, showing that each component contributes to the blood pressure effect, provided that other evidence supports dissimilar mechanisms of action and the doses in the combination are reasonably high on their dose-response curves. (lexology.com)
  • Upon completing either of the above factorial studies, a sponsor would not need to study combinations of lower approved doses to satisfy the combination rule, because the drugs' independent effects at lower doses can be assumed. (lexology.com)
  • Most drugs were effective in combinations when used in standard doses. (bidmc.org)
  • Therapy with the low to moderate doses of the two drugs in a combination agent more effectively lowers blood pressure than monotherapy with a higher dosage of either drug alone-and with fewer side effects. (aafp.org)
  • For one anti-inflammatory example, we show how such selectivity is achieved through differential expression of the drugs' targets in cell types associated with therapeutic, but not toxic, effects and validate its therapeutic relevance in a rat model of asthma. (nih.gov)
  • Kalinina OV, Wichmann O, Apic G, Russell RB (2011) Combinations of Protein-Chemical Complex Structures Reveal New Targets for Established Drugs. (plos.org)
  • The findings in laboratory animals "" both improved memory in our tests and evidence that the drug targets the biology for making memories in the brain "" places this drug on solid footing as a candidate therapeutic agent," said the study's lead author, Michela Gallagher. (redorbit.com)
  • Advances in target-based drug discovery strategies have enabled drug discovery groups in academia and industry to become very effective at generating molecules that are potent and selective against single targets. (frontiersin.org)
  • This drug combination targets a different pathway in the brain so could offer hope for those for whom the SSRIs don't work. (healthcanal.com)
  • Tell your doctor if you or anyone in your family drinks or has ever drunk large amounts of alcohol, uses or has ever used street drugs, or has overused prescription medications, or has had an overdose, or if you have or have ever had depression or another mental illness. (medlineplus.gov)
  • Taking certain medications with a hydrocodone combination product may increase the risk of serious or life-threatening breathing problems, sedation, or coma. (medlineplus.gov)
  • If you take a hydrocodone combination product with any of these medications and you develop any of the following symptoms, call your doctor immediately or seek emergency medical care: unusual dizziness, lightheadedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness. (medlineplus.gov)
  • Specifically, a report in the journal Hypertension finds that quarter-dose combinations of blood pressure-lowering medications appear to work better. (uspharmacist.com)
  • Results indicate that two medications in combination, each at a quarter dose, was just as effective as one blood pressure-lowering medication at a standard dose. (uspharmacist.com)
  • The study also determined that four medications in combination, each at a quarter dose, was nearly twice as effective as taking one blood pressure-lowering medication at the standard dose. (uspharmacist.com)
  • Data presented at a medical meeting in Philadelphia today showed the Ardea drug was no better at controlling gout than existing medications, including allopurinol, a cheap generic. (xconomy.com)
  • Our findings suggest that the combination of proteaseinhibitors and other anti-HIV medications can restore the immunesystem to a point where it can fight the CMV retinitis infection onits own," said Dr. Scott Whitcup, clinical director of NEI andfirst author of the JAMA letter. (nih.gov)
  • For decades, scientists have wrestled with the problem that trusted prescription medications can combine in dangerous ways, often placing Americans at risk when they take more than one drug. (expressnews.com)
  • The drugs include several widely prescribed medications, none of them linked to the cardiac condition on its own. (expressnews.com)
  • The prescriptions in question involve a combination of two medications, hydroxychloroquine sulfate (brand name Plaquenil) and azithromycin (brand name Zithromax). (thespec.com)
  • it seeks to work with UK-based investigators to develop and deliver high quality preclinical projects evaluating specific radiotherapy-drug combinations, to provide the necessary evidence base for early phase clinical trials. (ncri.org.uk)
  • Given these encouraging results, the U.S. Food and Drug Administration and Health Canada authorized the start of a Phase 3 clinical study. (eurekalert.org)
  • This antibacterial drug combination - already in clinical use for Gram-negative bacterial infections - could aid in stemming the growing global drug-resistant tuberculosis crisis. (eurekalert.org)
  • The results from this work were convincing enough that we launched phase I clinical trials of both drug combinations at the NIH Clinical Center. (cancer.gov)
  • The first pediatric study of a combination drug to treat the hepatitis C virus (HCV) infection in children and adolescents demonstrated 100 percent effectiveness in adolescents who completed the 12-week, phase II clinical trial. (cincinnatichildrens.org)
  • Looking forward, Faber said that he and his research team will continue to collaborate with AbbVie Inc., the pharmaceutical company responsible for manufacturing venetoclax, to transition the combination of venetoclax and epigenetic drugs into clinical trials for neuroblastoma. (medindia.net)
  • For clinical trial design, the guidance provides that a single phase 3, double-blind, randomized trial would generally be sufficient to demonstrate effectiveness of a combination of previously approved antihypertensive drugs. (lexology.com)
  • Sponsors of products that combine two or more previously marketed drugs or biologics may be able to rely on existing clinical and nonclinical safety data before proceeding with clinical trials of the proposed combination therapy, according to a new FDA guidance. (fdanews.com)
  • The experiment began with thousands of patient files, millions of prescription orders, billions of clinical measurements and a single question: Could big data be used to discover deadly drug combinations? (expressnews.com)
  • We further describe how the incorporation of high-throughput reverse phase protein microarrays with phenotypic screening can provide rational drug combination hypotheses but also confirm the mechanism-of-action of novel drug combinations, to facilitate future preclinical and clinical development strategies. (frontiersin.org)
  • Given the widespread use and strong track record of clinical success of combination therapy across complex diseases, it is surprising that most typical drug discovery strategies only consider drug combinations during late-stage development or as a risk mitigation strategy. (frontiersin.org)
  • RIVUR was a two-year clinical trial that randomized 607 children to receive the TMP/SMP drug combination or placebo. (infectioncontroltoday.com)
  • The team carried out many experiments in the laboratory and designed a mathematical framework - called mathematical analysis for general interactions of components (MAGIC) - that enabled them to study multiple drug combinations and anticipate their results. (medicalnewstoday.com)
  • Lead author of the study Krisztina M. Papp-Wallace, assistant professor of medicine at the School of Medicine and a research scientist at the Cleveland VA Medical Center explained, "By successfully combining these two drugs against this widespread form of bacteria, we hope to lay a foundation for eventually eradicating the infection. (news-medical.net)
  • They also will study whether the combination of drugs can prevent the development of osteoarthritis before symptoms develop. (news-medical.net)
  • The new study suggests that combining venetoclax with the new epigenetic drug may be even more effective. (medindia.net)
  • The purpose of this study is to compare the safety and effectiveness of taking lamivudine (3TC) plus zidovudine (ZDV) plus a protease inhibitor (PI) with taking the 3TC/ZDV combination tablet (Combivir) plus a PI. (clinicaltrials.gov)
  • In a recent study done in six European countries, investigators reviewed the medicines taken by about 1600 people and found that 46% were taking at least one pair of drugs that could interact. (diabetesselfmanagement.com)
  • India needs to ban the sale and manufacturing of fixed-dose drug combinations not approved by the CDSCO beginning with those which include drugs banned or unapproved internationally and, therefore, most likely to be harmful," explained Patricia McGettigan who led the study at Queen Mary University of London. (medindia.net)
  • Our research wholly supports the need for a complete overhaul of the new Drugs Bill and we urge the government of India to make this a priority," noted professor Allyson Pollock, global health expert and study co-author. (medindia.net)
  • This study was conducted to evaluate and compare two drug combinations of TIVA using propofol-ketamine and propofol-fentanyl and to study the induction, maintenance and recovery characteristics following anesthesia with these techniques. (nih.gov)
  • The study provides an in-depth analysis of the global drug-device combination products market with the current trends and future estimations from 2017 to 2025 to elucidate the imminent investment pockets. (openpr.com)
  • This is reflected in the findings of an in vitro study which will form the basis for developing a single drug that combats viral infections as well as freeing up blocked airways. (prlog.org)
  • A National Institutes of Health network study has confirmed that a combination of two drugs taken daily to reduce the chances of HIV infection among high-risk adults also works well and appears safe in males ages 15 to 17 years. (scienceblog.com)
  • The study published in JAMA Pediatrics, was funded by NIH's Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institute on Drug Abuse, and National Institute of Mental Health. (scienceblog.com)
  • Youth with poor kidney function and a history of bone fractures were excluded from the study because the drug combination may sometimes stress the kidneys and cause bone loss. (scienceblog.com)
  • In general, study participants tolerated the drug well, and there were no reports of effects on the kidneys or bones. (scienceblog.com)
  • The authors concluded that the lack of significant adverse health events during the study indicates that the drug is safe for males under age 18. (scienceblog.com)
  • In this study, we employ a computational approach, SynGeNet (Synergy from Gene expression and Network mining), which integrates transcriptomics-based connectivity mapping and network centrality analysis to analyze disease networks and predict drug combinations. (nature.com)
  • We validated synergistic drug combinations predicted by our method across all genomic subtypes using results from a high-throughput drug screening study across. (nature.com)
  • One systems-based approach employed in this study is the widely used connectivity mapping method to facilitate systematic comparison of gene expression profiles characterizing responses to drugs and biological states of interest using pattern-matching algorithms. (nature.com)
  • an early-stage study is being conducted in 54 healthy volunteers to look at the safety of the drug combination. (xconomy.com)
  • The purpose of this study is to compare the effectiveness of various combinations of anti-HIV drugs in HIV-positive men and women. (bioportfolio.com)
  • The purpose of this study is to see if it is safe and effective to give an anti-HIV drug combination of indinavir (IDV) plus stavudine (d4T) plus lamivudine (3TC) to HIV-infected children. (bioportfolio.com)
  • This study will also see how a combination of st. (bioportfolio.com)
  • In this study, we evaluated the relative activity of three commonly used sulfa drugs, sulfamethoxazole (Smx), dapsone (Dps), sulfachlorpyridazine (Scp), and also trimethoprim (Tmp), and assessed their combinations with the commonly prescribed Lyme antibiotics for activities against B. burgdorferi stationary phase cells. (prohealth.com)
  • The addition of etanercept was safe and had no impact on the concentration of the chemotherapy drugs in the body, the study found. (fdanews.com)
  • The Columbia scientists cautioned that the study, published earlier this month in the journal Drug Safety, does not prove cause and effect and that the results are preliminary. (expressnews.com)
  • Dr Bailey added: "Our study shows that using a combination of naltrexone and buprenorphine gives an antidepressant effect in mice, but without the problems of addiction that could be caused by using buprenorphine alone. (healthcanal.com)
  • New research led by scientists at the University of California, Los Angeles (UCLA) reveals that combining four or five antibiotics can prove surprisingly effective in killing off or slowing down the progression of drug-resistant bacteria. (medicalnewstoday.com)
  • They expected some of these combinations to perform well against bacteria - but surprisingly, they also found 1,676 four-drug combinations and 6,443 five-drug combinations to be equally effective. (medicalnewstoday.com)
  • This combination was tried on mice models with Pseudomonas infections and the results showed that the combination was more effective in killing the bacteria compared to either antibiotic alone. (news-medical.net)
  • Scientists at MIT report that by delivering a combination of antibiotic drugs and probiotics, they could eradicate two strains of drug-resistant bacteria that often infect wounds. (genengnews.com)
  • When MRSA and Pseudomonas aeruginosa growing in a lab dish were exposed to the combination of encapsulated Bio-K+ and tobramycin, all of the pathogenic bacteria were wiped out. (genengnews.com)
  • Because bacteria - especially Gram-negative strains - are becoming increasingly resistant to current antibiotics, investigators are studying the potential of combining two or more drugs to work together to combat resistant bacterial pathogens. (bidmc.org)
  • Drug combinations are a promising strategy to overcome the compensatory mechanisms and unwanted off-target effects that limit the utility of many potential drugs. (nih.gov)
  • These combinations were tested for their antitumor activity in several mouse models of human tumors, and additional experiments were performed to investigate the mechanisms by which these combinations kill tumor cells. (cancer.gov)
  • Computational methods are needed to efficiently model complex interactions of drug target pathways and identify mechanisms underlying drug combination synergy. (nature.com)
  • Finally, we prospectively validated the drug combination for BRAF -mutant melanoma that was top ranked by our approach, vemurafenib (BRAF inhibitor) + tretinoin (retinoic acid receptor agonist), using both in vitro and in vivo models of BRAF -mutant melanoma and RNA-sequencing analysis of drug-treated melanoma cells to validate the predicted mechanisms. (nature.com)
  • Widely studied drug delivery systems such as liposomes, dendrimers, polymeric nanoparticles, and water-soluble polymers can concurrently carry multiple anticancer drugs in one platform. (hindawi.com)
  • In the search for medication against Alzheimer's disease, scientists have focused - among other factors - on drugs that can break down Amyloid beta (A-beta). (medindia.net)
  • Terms like "combination drug" or "combination drug product" can be common shorthand for a FDC product (since most combination drug products are currently FDCs), although the latter is more precise if in fact referring to a mass-produced product having a predetermined combination of drugs and respective dosages (as opposed to customized polypharmacy via compounding). (wikipedia.org)
  • Initially, fixed-dose combination drug products were developed to target a single disease (such as with antiretroviral FDCs used against AIDS). (wikipedia.org)
  • Since FDCs are reviewed by regulating agencies (such as the Food and Drug Administration in the United States), the active ingredients used in the FDCs are unlikely to exhibit adverse drug interactions with each other. (wikipedia.org)
  • However, FDCs may interact with other drugs that a patient is taking, so the usual medical and pharmaceutical precautions against drug-drug interactions or DDIs remain warranted. (wikipedia.org)
  • In 2012, the Parliamentary Standing Committee on Health & Family Welfare reported that a very large number of FDCs had been licensed by state drug authorities without approval by the Central Drugs Standard Control Organization (CDSCO). (medindia.net)
  • Drug companies create FDCs as a way to extend their proprietary rights, increase prices, and improve marketability. (sciencebasedmedicine.org)
  • If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online ( http://www.fda.gov/Safety/MedWatch ) or by phone (1-800-332-1088). (medlineplus.gov)
  • The investigation is believed to be the first time anyone has discovered a potential drug interaction by searching for signals in the Food and Drug Administration's complaint archive, then confirming the findings through patient records and cellular testing. (expressnews.com)
  • The global drug-device combination products market was valued at $81,374 million in 2017 and is projected to reach $139,193 million by 2025 at a CAGR of 6.9% from 2018 to 2025. (openpr.com)
  • With his colleague, Dan Malone, RPh, PhD, Dr. Horn advised the Chicago Tribune which drug pairs represented either a serious problem or a potentially deadly combination. (peoplespharmacy.com)
  • 3 , 4 Discovering novel uses for existing drugs through drug repurposing or drug repositioning has also been an important goal in efforts to advance understanding of systems-level effects of large repertoires of chemical and pharmacological agents, and in doing so, potentially reduce the financial and labor costs associated with the drug discovery process. (nature.com)
  • Two years later, the results are in: The team has identified four drug combinations associated with a heart condition that can lead to a potentially fatal arrhythmia. (expressnews.com)
  • To find the potentially risky combinations, the Tribune enlisted the help of scientists at Columbia, who used sophisticated algorithms to analyze a massive government database of drug complaints for signs of the heart condition. (expressnews.com)
  • Systems medicine approaches and related computational methods have provided new and powerful means to aid in various aspects of the drug discovery process via modeling complex, multi-dimensional phenotypes that seek to overcome reductionist approaches to discovery science. (nature.com)
  • While lifestyle advice alone was associated with weight loss at six and 12 months, the results were less impressive than those achieved with anti-obesity drugs. (netdoctor.co.uk)
  • The FDA based its latest approval of the drug on results from a Phase III trial referred to as RAINBOW, which compared Cyramza plus paclitaxel to placebo plus paclitaxel. (biospace.com)
  • Dr. Nagourney used the results of the EVA analysis to identify the combination for this patient, resulting in a remission that lasted several years. (cancernetwork.com)
  • If results are good, Ardea will test the drug combination in people with gout. (xconomy.com)
  • However, until we have those results, the use of these drugs appears to provide more benefit than risk in these children. (infectioncontroltoday.com)
  • Herewith, we demonstrated the preparation, characterization and in vitro antitumor effects of Ara-C and DNR loaded GP-PLGA-modified bacterial magnetosomes (BMs) (ADBMs-P). The results show that this new system is stable and exhibits optimal drug-loading properties. (mdpi.com)
  • The selective coating is utilized to ensure that the specific drugs, agents or compounds come into contact with or are delivered to the appropriate tissues and/or fluids for maximum effectiveness. (google.com)
  • The NCI ALMANAC includes data on more than 5,000 pairs of FDA-approved drugs that were tested against the NCI-60-a total of 300,000 experiments. (cancer.gov)
  • We began by conducting follow-up experiments on a subset of drug pairs identified in the database that exhibited potent cell-killing effects. (cancer.gov)
  • In an ideal world, no pharmacy would have dispensed any of these drug pairs, period! (peoplespharmacy.com)
  • The team then used 380,000 electronic hospital patient files to confirm which drug pairs were indeed associated with an increased risk. (expressnews.com)
  • Drug pairs targeting key signaling pathways resulted in synergies across a broad spectrum of genetic backgrounds but often yielded only cytostatic responses. (aacrjournals.org)
  • 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. (diabetesselfmanagement.com)
  • The findings go against the prevalent view that such drug combinations are ineffective, or that mixing different antibiotics leads to the drugs' benefits canceling each other out. (medicalnewstoday.com)
  • We expect several of these combinations, or more, will work much better than existing antibiotics. (medicalnewstoday.com)
  • Using these tools, Tekin and colleagues examined how every possible combination of four and five antibiotics affected a strain of Escherichia coli . (medicalnewstoday.com)
  • A Reuters investigation revealed in December that a unit of Abbott in India was selling a combination of the antibiotics cefixime and azithromycin without approval from the central government. (reuters.com)
  • Investigators at Beth Israel Deaconess Medical Center (BIDMC) have now demonstrated that existing antibiotics, some of which have been in use for decades, may have potent activity against such strains when used in combination. (bidmc.org)
  • We found that sulfa drugs combined with other antibiotics were more active than their respective single drugs and that four-drug combinations were more active than three-drug combinations. (prohealth.com)
  • The development of combination products leads to better management of chronic disorders, reduces the levels of pain, minimizes hospital stays, and provides better healthcare cost efficiency. (openpr.com)
  • If you are taking these drugs together, your healthcare provider may need to adjust your dose of propranolol. (emedtv.com)
  • If you are taking these drugs together, your healthcare provider should monitor the level of theophylline in your blood, especially when you are starting or stopping Luvox. (emedtv.com)
  • Consequently, reductionist target directed drug-discovery approaches are not appropriately tailored toward identifying and optimizing multi-targeted therapeutics or rational drug combinations for complex disease. (frontiersin.org)
  • Reuters also found chemists who were selling the drug to prevent post-operative infection and for respiratory problems. (reuters.com)
  • The drug works by forming a protective layer on the nasal mucosa to prevent infection by cold viruses. (prlog.org)
  • The drug is the cornerstone of pre-exposure prophylaxis ( PrEP ), a strategy in which healthy people at risk for HIV infection take one or more anti-HIV drugs to reduce this risk. (scienceblog.com)
  • Levels of the drug sufficient to prevent HIV infection were found in 54 percent of participants by week four, 49 percent by week 12, 28 percent by week 24, and 22 percent by week 48. (scienceblog.com)
  • Long-term use of a drug combination reduces the risk of recurrent urinary tract infection by up to 80 percent in children with the urinary condition vesicoureteral reflux compared to placebo, according to research funded by the National Institutes of Health. (infectioncontroltoday.com)
  • The risk of recurrent infection was cut by 50 percent in children with VUR using the drug combination trimethoprim/sulfamethoxazole (TMP/SMZ). (infectioncontroltoday.com)
  • We shouldn't limit ourselves to just single drugs or two-drug combinations in our medical toolbox. (medicalnewstoday.com)
  • Ability to compose combined profiles of for example pharmacokinetics, effects and adverse effects that may be specific for the relative dosages in a given FDC product, providing a simpler overview compared to when looking at the profiles of each single drug individually. (wikipedia.org)
  • Using large scale simulations of bacterial metabolism and 94,110 multi-dose experiments relevant to diverse diseases, we provide evidence that synergistic drug combinations are generally more specific to particular cellular contexts than are single agent activities. (nih.gov)
  • Single agent (horizontal frames) and fixed dose ratio combination curves (diagonal frames) are extracted from both dose matrices. (nih.gov)
  • Lead author Dr Laura Gray, whose findings are published in the journal Obesity Review, said: 'This is the first review to combine all available evidence for anti-obesity drugs in a single analysis. (netdoctor.co.uk)
  • That meeting focused in particular on running Phase 2 trials on a continuous, adaptive platform that could test both combinations and single drugs against a shared control group. (alzforum.org)
  • Once the effect of each compound as a single agent is removed, an Excess Matrix is generated that provides a simple visual representation of information about combination activity at the multiple concentrations and ratios of the two drugs and where synergies or antagonism can be seen. (horizondiscovery.com)