Administration, Oral: The giving of drugs, chemicals, or other substances by mouth.Gene Dosage: The number of copies of a given gene present in the cell of an organism. An increase in gene dosage (by GENE DUPLICATION for example) can result in higher levels of gene product formation. GENE DOSAGE COMPENSATION mechanisms result in adjustments to the level GENE EXPRESSION when there are changes or differences in gene dosage.Dosage Compensation, Genetic: Genetic mechanisms that allow GENES to be expressed at a similar level irrespective of their GENE DOSAGE. This term is usually used in discussing genes that lie on the SEX CHROMOSOMES. Because the sex chromosomes are only partially homologous, there is a different copy number, i.e., dosage, of these genes in males vs. females. In DROSOPHILA, dosage compensation is accomplished by hypertranscription of genes located on the X CHROMOSOME. In mammals, dosage compensation of X chromosome genes is accomplished by random X CHROMOSOME INACTIVATION of one of the two X chromosomes in the female.Drug Administration Schedule: Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience.Dosage Forms: Completed forms of the pharmaceutical preparation in which prescribed doses of medication are included. They are designed to resist action by gastric fluids, prevent vomiting and nausea, reduce or alleviate the undesirable taste and smells associated with oral administration, achieve a high concentration of drug at target site, or produce a delayed or long-acting drug effect.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Injections, Intravenous: Injections made into a vein for therapeutic or experimental purposes.United States Food and Drug Administration: An agency of the PUBLIC HEALTH SERVICE concerned with the overall planning, promoting, and administering of programs pertaining to maintaining standards of quality of foods, drugs, therapeutic devices, etc.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Drug Administration Routes: The various ways of administering a drug or other chemical to a site in a patient or animal from where the chemical is absorbed into the blood and delivered to the target tissue.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.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Administration, Intranasal: Delivery of medications through the nasal mucosa.Injections, Intraperitoneal: Forceful administration into the peritoneal cavity of liquid medication, nutrient, or other fluid through a hollow needle piercing the abdominal wall.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.Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity.Injections, Subcutaneous: Forceful administration under the skin of liquid medication, nutrient, or other fluid through a hollow needle piercing the skin.Mice, Inbred C57BLLiver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Injections, Intramuscular: Forceful administration into a muscle of liquid medication, nutrient, or other fluid through a hollow needle piercing the muscle and any tissue covering it.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.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)Administration, Rectal: The insertion of drugs into the rectum, usually for confused or incompetent patients, like children, infants, and the very old or comatose.Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug.Double-Blind Method: A method of studying a drug or procedure in which both the subjects and investigators are kept unaware of who is actually getting which specific treatment.Administration, Topical: The application of drug preparations to the surfaces of the body, especially the skin (ADMINISTRATION, CUTANEOUS) or mucous membranes. This method of treatment is used to avoid systemic side effects when high doses are required at a localized area or as an alternative systemic administration route, to avoid hepatic processing for example.Biological Availability: The extent to which the active ingredient of a drug dosage form becomes available at the site of drug action or in a biological medium believed to reflect accessibility to a site of action.Treatment 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.Administration, Intravenous: Delivery of substances through VENIPUNCTURE into the VEINS.Tissue Distribution: Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios.Injections, Intraventricular: Injections into the cerebral ventricles.Mice, Inbred BALB CCross-Over Studies: Studies comparing two or more treatments or interventions in which the subjects or patients, upon completion of the course of one treatment, are switched to another. In the case of two treatments, A and B, half the subjects are randomly allocated to receive these in the order A, B and half to receive them in the order B, A. A criticism of this design is that effects of the first treatment may carry over into the period when the second is given. (Last, A Dictionary of Epidemiology, 2d ed)Administration, Cutaneous: The application of suitable drug dosage forms to the skin for either local or systemic effects.Rats, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.Dogs: The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)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.Body Weight: The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.Infusions, Parenteral: The administration of liquid medication, nutrient, or other fluid through some other route than the alimentary canal, usually over minutes or hours, either by gravity flow or often by infusion pumping.Kidney: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.Blood Pressure: PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS.Metabolic Clearance Rate: Volume of biological fluid completely cleared of drug metabolites as measured in unit time. Elimination occurs as a result of metabolic processes in the kidney, liver, saliva, sweat, intestine, heart, brain, or other site.Drug Therapy, Combination: Therapy with two or more separate preparations given for a combined effect.Brain: The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.Chromatography, High Pressure Liquid: Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.Administration, Inhalation: The administration of drugs by the respiratory route. It includes insufflation into the respiratory tract.Administration, Sublingual: Administration of a soluble dosage form by placement under the tongue.Delayed-Action Preparations: Dosage forms of a drug that act over a period of time by controlled-release processes or technology.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Chemistry, Pharmaceutical: Chemistry dealing with the composition and preparation of agents having PHARMACOLOGIC ACTIONS or diagnostic use.Drug Combinations: Single preparations containing two or more active agents, for the purpose of their concurrent administration as a fixed dose mixture.Plant Extracts: Concentrated pharmaceutical preparations of plants obtained by removing active constituents with a suitable solvent, which is evaporated away, and adjusting the residue to a prescribed standard.Tablets: Solid dosage forms, of varying weight, size, and shape, which may be molded or compressed, and which contain a medicinal substance in pure or diluted form. (Dorland, 28th ed)Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from DRUG RESISTANCE wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from MAXIMUM TOLERATED DOSE and NO-OBSERVED-ADVERSE-EFFECT LEVEL.Behavior, Animal: The observable response an animal makes to any situation.Organ Size: The measurement of an organ in volume, mass, or heaviness.Analysis of Variance: A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable.Injections: Introduction of substances into the body using a needle and syringe.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle.Drug Dosage Calculations: Math calculations done for preparing appropriate doses of medicines, taking into account conversions of WEIGHTS AND MEASURES. Mistakes are one of the sources of MEDICATION ERRORS.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Pregnancy: The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.Mice, Inbred ICRInjections, Spinal: Introduction of therapeutic agents into the spinal region using a needle and syringe.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.Analgesics, Opioid: Compounds with activity like OPIATE ALKALOIDS, acting at OPIOID RECEPTORS. Properties include induction of ANALGESIA or NARCOSIS.Lung: Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.Anti-Bacterial Agents: Substances that reduce the growth or reproduction of BACTERIA.X Chromosome: The female sex chromosome, being the differential sex chromosome carried by half the male gametes and all female gametes in human and other male-heterogametic species.Heart Rate: The number of times the HEART VENTRICLES contract per unit of time, usually per minute.Estradiol: The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids.Rats, Inbred F344Drug Evaluation, Preclinical: Preclinical testing of drugs in experimental animals or in vitro for their biological and toxic effects and potential clinical applications.Anti-Inflammatory Agents, Non-Steroidal: Anti-inflammatory agents that are non-steroidal in nature. In addition to anti-inflammatory actions, they have analgesic, antipyretic, and platelet-inhibitory actions.They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins. Inhibition of prostaglandin synthesis accounts for their analgesic, antipyretic, and platelet-inhibitory actions; other mechanisms may contribute to their anti-inflammatory effects.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.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.Mice, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.Administration, Buccal: Administration of a soluble dosage form between the cheek and gingiva. It may involve direct application of a drug onto the buccal mucosa, as by painting or spraying.Analgesics: Compounds capable of relieving pain without the loss of CONSCIOUSNESS.Hemodynamics: The movement and the forces involved in the movement of the blood through the CARDIOVASCULAR SYSTEM.Motor Activity: The physical activity of a human or an animal as a behavioral phenomenon.Prodrugs: A compound that, on administration, must undergo chemical conversion by metabolic processes before becoming the pharmacologically active drug for which it is a prodrug.Self Administration: Administration of a drug or chemical by the individual under the direction of a physician. It includes administration clinically or experimentally, by human or animal.Intestinal Absorption: Uptake of substances through the lining of the INTESTINES.Piperidines: A family of hexahydropyridines.Blood Glucose: Glucose in blood.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.Spleen: An encapsulated lymphatic organ through which venous blood filters.Capsules: Hard or soft soluble containers used for the oral administration of medicine.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Drug Synergism: The action of a drug in promoting or enhancing the effectiveness of another drug.Prospective Studies: Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group.Injections, Intra-Arterial: Delivery of drugs into an artery.Absorption: The physical or physiological processes by which substances, tissue, cells, etc. take up or take in other substances or energy.Anti-Inflammatory Agents: Substances that reduce or suppress INFLAMMATION.Kinetics: The rate dynamics in chemical or physical systems.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.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.Drug Approval: Process that is gone through in order for a drug to receive approval by a government regulatory agency. This includes any required pre-clinical or clinical testing, review, submission, and evaluation of the applications and test results, and post-marketing surveillance of the drug.Eating: The consumption of edible substances.United StatesCells, 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.Pain: An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.Hydrocortisone: The main glucocorticoid secreted by the ADRENAL CORTEX. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions.Drug Carriers: Forms to which substances are incorporated to improve the delivery and the effectiveness of drugs. Drug carriers are used in drug-delivery systems such as the controlled-release technology to prolong in vivo drug actions, decrease drug metabolism, and reduce drug toxicity. Carriers are also used in designs to increase the effectiveness of drug delivery to the target sites of pharmacological actions. Liposomes, albumin microspheres, soluble synthetic polymers, DNA complexes, protein-drug conjugates, and carrier erythrocytes among others have been employed as biodegradable drug carriers.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Insulin: A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).Glucocorticoids: A group of CORTICOSTEROIDS that affect carbohydrate metabolism (GLUCONEOGENESIS, liver glycogen deposition, elevation of BLOOD SUGAR), inhibit ADRENOCORTICOTROPIC HORMONE secretion, and possess pronounced anti-inflammatory activity. They also play a role in fat and protein metabolism, maintenance of arterial blood pressure, alteration of the connective tissue response to injury, reduction in the number of circulating lymphocytes, and functioning of the central nervous system.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alterations may be divided into METABOLIC DETOXICATION, PHASE I and METABOLIC DETOXICATION, PHASE II.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.Naloxone: A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors.Pain Measurement: Scales, questionnaires, tests, and other methods used to assess pain severity and duration in patients or experimental animals to aid in diagnosis, therapy, and physiological studies.Phytotherapy: Use of plants or herbs to treat diseases or to alleviate pain.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.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.Testosterone: A potent androgenic steroid and major product secreted by the LEYDIG CELLS of the TESTIS. Its production is stimulated by LUTEINIZING HORMONE from the PITUITARY GLAND. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to DIHYDROTESTOSTERONE or ESTRADIOL.Dopamine: One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.Genetic Therapy: Techniques and strategies which include the use of coding sequences and other conventional or radical means to transform or modify cells for the purpose of treating or reversing disease conditions.Dexamethasone: An anti-inflammatory 9-fluoro-glucocorticoid.Placebos: Any dummy medication or treatment. Although placebos originally were medicinal preparations having no specific pharmacological activity against a targeted condition, the concept has been extended to include treatments or procedures, especially those administered to control groups in clinical trials in order to provide baseline measurements for the experimental protocol.Cytokines: Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.Progesterone: The major progestational steroid that is secreted primarily by the CORPUS LUTEUM and the PLACENTA. Progesterone acts on the UTERUS, the MAMMARY GLANDS and the BRAIN. It is required in EMBRYO IMPLANTATION; PREGNANCY maintenance, and the development of mammary tissue for MILK production. Progesterone, converted from PREGNENOLONE, also serves as an intermediate in the biosynthesis of GONADAL STEROID HORMONES and adrenal CORTICOSTEROIDS.Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.Animals, Newborn: Refers to animals in the period of time just after birth.Growth Hormone: A polypeptide that is secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). Growth hormone, also known as somatotropin, stimulates mitosis, cell differentiation and cell growth. Species-specific growth hormones have been synthesized.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Genetic Vectors: DNA molecules capable of autonomous replication within a host cell and into which other DNA sequences can be inserted and thus amplified. Many are derived from PLASMIDS; BACTERIOPHAGES; or VIRUSES. They are used for transporting foreign genes into recipient cells. Genetic vectors possess a functional replicator site and contain GENETIC MARKERS to facilitate their selective recognition.Lipopolysaccharides: Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed)Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Antioxidants: Naturally occurring or synthetic substances that inhibit or retard the oxidation of a substance to which it is added. They counteract the harmful and damaging effects of oxidation in animal tissues.Hypnotics and Sedatives: Drugs used to induce drowsiness or sleep or to reduce psychological excitement or anxiety.Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.Administration, Intravaginal: The insertion of drugs into the vagina to treat local infections, neoplasms, or to induce labor. The dosage forms may include medicated pessaries, irrigation fluids, and suppositories.Models, Animal: Non-human animals, selected because of specific characteristics, for use in experimental research, teaching, or testing.Body Temperature: The measure of the level of heat of a human or animal.Neoplasms, Experimental: Experimentally induced new abnormal growth of TISSUES in animals to provide models for studying human neoplasms.Tumor Necrosis Factor-alpha: Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.Diazepam: A benzodiazepine with anticonvulsant, anxiolytic, sedative, muscle relaxant, and amnesic properties and a long duration of action. Its actions are mediated by enhancement of GAMMA-AMINOBUTYRIC ACID activity.PiperazinesAnalgesics, Non-Narcotic: A subclass of analgesic agents that typically do not bind to OPIOID RECEPTORS and are not addictive. Many non-narcotic analgesics are offered as NONPRESCRIPTION DRUGS.Pyridines: Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.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.Gonadotropin-Releasing Hormone: A decapeptide that stimulates the synthesis and secretion of both pituitary gonadotropins, LUTEINIZING HORMONE and FOLLICLE STIMULATING HORMONE. GnRH is produced by neurons in the septum PREOPTIC AREA of the HYPOTHALAMUS and released into the pituitary portal blood, leading to stimulation of GONADOTROPHS in the ANTERIOR PITUITARY GLAND.Bile: An emulsifying agent produced in the LIVER and secreted into the DUODENUM. Its composition includes BILE ACIDS AND SALTS; CHOLESTEROL; and ELECTROLYTES. It aids DIGESTION of fats in the duodenum.Narcotic Antagonists: Agents inhibiting the effect of narcotics on the central nervous system.Luteinizing Hormone: A major gonadotropin secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). Luteinizing hormone regulates steroid production by the interstitial cells of the TESTIS and the OVARY. The preovulatory LUTEINIZING HORMONE surge in females induces OVULATION, and subsequent LUTEINIZATION of the follicle. LUTEINIZING HORMONE consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH and FSH), but the beta subunit is unique and confers its biological specificity.Swine: Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA).Infusion Pumps: Fluid propulsion systems driven mechanically, electrically, or osmotically that are used to inject (or infuse) over time agents into a patient or experimental animal; used routinely in hospitals to maintain a patent intravenous line, to administer antineoplastic agents and other drugs in thromboembolism, heart disease, diabetes mellitus (INSULIN INFUSION SYSTEMS is also available), and other disorders.Therapeutic Equivalency: The relative equivalency in the efficacy of different modes of treatment of a disease, most often used to compare the efficacy of different pharmaceuticals to treat a given disease.Vasodilator Agents: Drugs used to cause dilation of the blood vessels.Drug Compounding: The preparation, mixing, and assembling of a drug. (From Remington, The Science and Practice of Pharmacy, 19th ed, p1814)Leukocyte Count: The number of WHITE BLOOD CELLS per unit volume in venous BLOOD. A differential leukocyte count measures the relative numbers of the different types of white cells.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.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.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.Microdialysis: A technique for measuring extracellular concentrations of substances in tissues, usually in vivo, by means of a small probe equipped with a semipermeable membrane. Substances may also be introduced into the extracellular space through the membrane.Adjuvants, Immunologic: Substances that augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. The classical agents (Freund's adjuvant, BCG, Corynebacterium parvum, et al.) contain bacterial antigens. Some are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy of many biological response modifiers is related to their antigen-specific immunoadjuvanticity.Neoplasm Transplantation: Experimental transplantation of neoplasms in laboratory animals for research purposes.Anticonvulsants: Drugs used to prevent SEIZURES or reduce their severity.Erythropoietin: Glycoprotein hormone, secreted chiefly by the KIDNEY in the adult and the LIVER in the FETUS, that acts on erythroid stem cells of the BONE MARROW to stimulate proliferation and differentiation.Diabetes Mellitus, Experimental: Diabetes mellitus induced experimentally by administration of various diabetogenic agents or by PANCREATECTOMY.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).Pyrazoles: Azoles of two nitrogens at the 1,2 positions, next to each other, in contrast with IMIDAZOLES in which they are at the 1,3 positions.Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states.Anti-Anxiety Agents: Agents that alleviate ANXIETY, tension, and ANXIETY DISORDERS, promote sedation, and have a calming effect without affecting clarity of consciousness or neurologic conditions. ADRENERGIC BETA-ANTAGONISTS are commonly used in the symptomatic treatment of anxiety but are not included here.Haloperidol: A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279)Hypoglycemic Agents: Substances which lower blood glucose levels.Drug Labeling: Use of written, printed, or graphic materials upon or accompanying a drug container or wrapper. It includes contents, indications, effects, dosages, routes, methods, frequency and duration of administration, warnings, hazards, contraindications, side effects, precautions, and other relevant information.Neuroprotective Agents: Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids.Retrospective Studies: Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons.Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures.Mice, Inbred C3HNorepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic.United States Department of Veterans Affairs: A cabinet department in the Executive Branch of the United States Government concerned with overall planning, promoting, and administering programs pertaining to VETERANS. It was established March 15, 1989 as a Cabinet-level position.Regional Blood Flow: The flow of BLOOD through or around an organ or region of the body.Genes, X-Linked: Genes that are located on the X CHROMOSOME.Ovariectomy: The surgical removal of one or both ovaries.Central Nervous System Stimulants: A loosely defined group of drugs that tend to increase behavioral alertness, agitation, or excitation. They work by a variety of mechanisms, but usually not by direct excitation of neurons. The many drugs that have such actions as side effects to their main therapeutic use are not included here.Medication Errors: Errors in prescribing, dispensing, or administering medication with the result that the patient fails to receive the correct drug or the indicated proper drug dosage.Drug-Induced Liver Injury: A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.Drugs, Chinese Herbal: Chinese herbal or plant extracts which are used as drugs to treat diseases or promote general well-being. The concept does not include synthesized compounds manufactured in China.Acute Disease: Disease having a short and relatively severe course.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.Adrenocorticotropic Hormone: An anterior pituitary hormone that stimulates the ADRENAL CORTEX and its production of CORTICOSTEROIDS. ACTH is a 39-amino acid polypeptide of which the N-terminal 24-amino acid segment is identical in all species and contains the adrenocorticotrophic activity. Upon further tissue-specific processing, ACTH can yield ALPHA-MSH and corticotrophin-like intermediate lobe peptide (CLIP).Suppositories: Medicated dosage forms that are designed to be inserted into the rectal, vaginal, or urethral orifice of the body for absorption. Generally, the active ingredients are packaged in dosage forms containing fatty bases such as cocoa butter, hydrogenated oil, or glycerogelatin that are solid at room temperature but melt or dissolve at body temperature.Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator.Sulfonamides: A group of compounds that contain the structure SO2NH2.Sex Chromosomes: The homologous chromosomes that are dissimilar in the heterogametic sex. There are the X CHROMOSOME, the Y CHROMOSOME, and the W, Z chromosomes (in animals in which the female is the heterogametic sex (the silkworm moth Bombyx mori, for example)). In such cases the W chromosome is the female-determining and the male is ZZ. (From King & Stansfield, A Dictionary of Genetics, 4th ed)Corticosterone: An adrenocortical steroid that has modest but significant activities as a mineralocorticoid and a glucocorticoid. (From Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed, p1437)Drug Monitoring: The process of observing, recording, or detecting the effects of a chemical substance administered to an individual therapeutically or diagnostically.Intestines: The section of the alimentary canal from the STOMACH to the ANAL CANAL. It includes the LARGE INTESTINE and SMALL INTESTINE.Propranolol: A widely used non-cardioselective beta-adrenergic antagonist. Propranolol has been used for MYOCARDIAL INFARCTION; ARRHYTHMIA; ANGINA PECTORIS; HYPERTENSION; HYPERTHYROIDISM; MIGRAINE; PHEOCHROMOCYTOMA; and ANXIETY but adverse effects instigate replacement by newer drugs.Feces: Excrement from the INTESTINES, containing unabsorbed solids, waste products, secretions, and BACTERIA of the DIGESTIVE SYSTEM.Device Approval: Process that is gone through in order for a device to receive approval by a government regulatory agency. This includes any required preclinical or clinical testing, review, submission, and evaluation of the applications and test results, and post-marketing surveillance. It is not restricted to FDA.Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes.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.Drug Stability: The chemical and physical integrity of a pharmaceutical product.
  • The recommended target dosage of SUBOXONE sublingual film during maintenance is 16 mg/4 mg buprenorphine/naloxone/day as a single daily dose. (drugs.com)
  • To reduce dose dependent side-effects and frequency of administration especially in the elderly hypertensive patients. (authorstream.com)
  • For maintenance, once dosage has been titrated to a level that provides adequate pain relief and tolerable adverse effects, patients should generally use only one dose of the appropriate strength per breakthrough pain episode. (thefreedictionary.com)
  • The dose and frequency of administration will vary with the indication and dosage form. (rxwiki.com)
  • Through buccal drug delivery system, the desired therapeutic dose of the drug gets immediately absorbed into plasma and the consistency of the concentration can be maintained throughout the duration of the treatment. (marketresearchreports.biz)
  • The initial dose of Abstral used should be 100 micrograms, titrating upwards as necessary through the range of available dosage strengths. (medicines.org.uk)
  • Se hicieron búsquedas en el Registro Cochrane Central de Ensayos Controlados (Cochrane Central Register of Controlled Trials) (CENTRAL) ( The Cochrane Library, asthalin syrup dose Número 2, 2005), MEDLINE (enero 1966 hasta junio 2005), y EMBASE (1988 hasta junio 2005). (train4mastery.com)
  • Particularly, an ultrarapid metabolizer of cyp2d6 may ever increase likelihood of a high from a lower dose of Buprenorphine (oral/buccal) due references to the fact that some of the buprenorphine is fully metabolized at a faster rate. (sbolot.org)
  • 8. Adrian C. L., Olin H. B., Dalhoff K., Jacobsen J. In vivo human buccal permeability of nicotine. (prolekare.cz)
  • Spiramycin has also been shown to greatly reduce the capacity of strains of Gram-positive cocci to adhere to human buccal cells. (nih.gov)
  • Stable regimen is defined as no change in AED regimen for at least 30 days before the first study drug administration and no change anticipated in the prescribed AED regimen over the course of study participation. (clinicaltrials.gov)
  • The ease of administration and ability to terminate drug delivery when required makes it a potential and attractive route of drug delivery. (authorstream.com)
  • Advantages of Mucoadhesive buccal drug delivery system Ease of administration. (authorstream.com)
  • The most comprehensive survey of dietary supplement use in the United States was conducted by the Food and Drug Administration (FDA) in 1980 through telephone interviews with 2,991 representative Americans over 15 years of age (Stewart et al. (nap.edu)
  • The disorder is more common in women than in men and in the elderly than in the young, and incidence is related to drug dosage and duration of treatment. (thefreedictionary.com)
  • The reason all your Phenytoin sodium dosage calculation is no longer proved effective may be because you have built up a tolerance to the drug, or creating even a tolerance to phenytoin. (gonzoz.com)
  • In order to optimise drug delivery to, or via, the buccal cavity, the use of adhesive dosage forms has been investigated [ 2 ]. (ijpsonline.com)
  • The buccal film has been increasingly used for administration because of advantages that the drug is directly available to the systemic circulation, avoidance of first pass metabolism, rapid onset of action, prolonged drug release and also easy removal of film from the site of application. (ijpsonline.com)
  • 3. Salamat-Miller N., Chittchang M., Johnston T. P. The use of mucoadhesive polymers in buccal drug delivery. (prolekare.cz)
  • 4. Sudhakar Y., Kuotsu K., Bandyopadhyay A. K. Buccal bioadhesive drug delivery - a promising option for orally less efficient drugs. (prolekare.cz)
  • BUNAVAIL was designed using BDSI's advanced drug delivery technology, BioErodible MucoAdhesive (BEMA), allowing for the efficient and convenient delivery of buprenorphine, while potentially overcoming some of the administration challenges presented by the sublingual (under the tongue) dosage forms currently available. (centerwatch.com)
  • In reservoir type, the buccal path is fabricated in a reservoir system, consisting of a cavity for drug and adhesives separated from the drug. (marketresearchreports.biz)
  • Furthermore, presence of major players in the market and availability of drugs is likely to boost the growth of the global buccal drug delivery system market during the forecast period. (marketresearchreports.biz)
  • Nevertheless, technological advancement and rise in mergers and acquisitions are expected to propel the global buccal drug delivery system market during the forecast period. (marketresearchreports.biz)
  • By end-user, the global buccal drug delivery system market can be categorized into hospitals, clinics, and others. (marketresearchreports.biz)
  • Geographically, the global buccal drug delivery system market can be divided into North America, Europe, Asia Pacific, Latin America, and Middle East & Africa. (marketresearchreports.biz)
  • North America held the leading share of the global buccal drug delivery system market in 2017, owing to highly developed pharmaceutical industry, high rate of diagnosis and treatment of diseases, well-established health care infrastructure, presence of major players, high awareness of the product among end-users, and technological advancements in the region. (marketresearchreports.biz)
  • In Europe, Germany, France, and the U.K. accounted for major share of the buccal drug delivery system market in 2017, while the market in Italy and Spain is expected to witness significant growth during the forecast period. (marketresearchreports.biz)
  • Highly developed health care industry, high rate of diagnosis and treatment of diseases, availability of drugs, presence of major players, and participation of small companies (particularly from Germany) in the market are the key factors which supported Germany, France, and the U.K. to capture the leading share of the buccal drug delivery systems market in Europe in 2017. (marketresearchreports.biz)
  • Developing health care infrastructure and technological advancements are likely to propel the growth of the buccal drug delivery systems market in Italy and Spain in the next few years. (marketresearchreports.biz)
  • In Asia, China and Japan held the dominant share of the buccal drug delivery system market in 2017. (marketresearchreports.biz)
  • The buccal drug delivery system market in India is estimated to grow at a significant CAGR in the near future, owing to the developing pharmaceutical industry, presence of well-established domestic players, and intense competition between domestic and international players in the country. (marketresearchreports.biz)
  • Underdeveloped pharmaceutical industry and lack of awareness about buccal drug delivery system are likely to hamper the growth of the buccal drug delivery systems market in Latin America and Middle East & Africa during the forecast period. (marketresearchreports.biz)
  • The Food and Drug Administration (FDA) has approved selegiline, which will be the first transdermal (skin) patch for use in the treatment of major depression in adults. (newsinferno.com)
  • Consequently, bioadhesive polymers have extensively been employed in buccal drug delivery systems. (ronaldweinland.info)
  • What are the six 'rights' you must verify before drug administration? (studystack.com)
  • How easy is the drug dosage to establish via the inhalation route? (studystack.com)
  • While the drug is not a cure for these conditions, it can help symptoms heal faster.Learn about zovirax (acyclovir) may treat, uses, dosage, side effects, drug interactions, warnings, patient labeling, reviews, and related medications.Aciclovir is used to treat two common viral infections varicellazoster and herpes simplex. (avto-trends.ru)
  • The dosage of SUBOXONE sublingual film from Day 3 onwards should be progressively adjusted in increments/decrements of 2 mg/0.5 mg or 4 mg/1 mg buprenorphine/naloxone to a level that holds the patient in treatment and suppresses opioid withdrawal signs and symptoms. (drugs.com)
  • Med baclofen tab 10mg is a buccal film which provides faster delivery of baclofen, a partial opioid agonist and schedule iii controlled dangerous substance. (gonzoz.com)
  • In liturgy the dosage range for lips which Cal - mag (one to one) with potass & zinc is overwhelmingly approved, potassium produces typical opioid agonist side effects. (sbolot.org)
  • Looking at the structure of this steroid, we see it is basically just testosterone with an added methyl group at the c-17 alpha position (a c-17 alpha alkylated substance), which allows for oral administration. (anabolic.org)
  • A method and system to prevent sore throat infections in humans includes the administration of an active ingredient to a site on the mucus membranes of the. (patents.com)
  • Pluronic F-127 gels incorporating highly purified unsaturated fatty acids for buccal delivery of insulin. (naver.com)
  • 24. Vetchý D., Landová H., Gajdziok J., Doležel P., Daněk Z., Štembírek J. Determination of dependencies among in vitro and in vivo properties of prepared mucoadhesive buccal films using multivariate data analysis. (prolekare.cz)
  • See Appendix 1 for examples of dosage preparations, frequencies of use and directions for use, according to cited references. (gc.ca)