Administration, Oral: The giving of drugs, chemicals, or other substances by mouth.Drug Administration Schedule: Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience.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.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.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.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.Time Factors: Elements of limited time intervals, contributing to particular results or situations.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.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.Injections, Subcutaneous: Forceful administration under the skin of liquid medication, nutrient, or other fluid through a hollow needle piercing the skin.Administration, Rectal: The insertion of drugs into the rectum, usually for confused or incompetent patients, like children, infants, and the very old or comatose.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Mice, Inbred C57BLBiological 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.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.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.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.Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity.Administration, Intravenous: Delivery of substances through VENIPUNCTURE into the VEINS.Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug.Injections, Intraventricular: Injections into the cerebral ventricles.Mice, Inbred BALB CRats, 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.Administration, Cutaneous: The application of suitable drug dosage forms to the skin for either local or systemic effects.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.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)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.Cross-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)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.Blood Pressure: PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS.Administration, Sublingual: Administration of a soluble dosage form by placement under the tongue.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.Administration, Inhalation: The administration of drugs by the respiratory route. It includes insufflation into the respiratory tract.Kidney: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.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.Body Weight: The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.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.Behavior, Animal: The observable response an animal makes to any situation.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.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.Recombinant Proteins: Proteins prepared by recombinant DNA technology.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.Injections: Introduction of substances into the body using a needle and syringe.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, Spinal: Introduction of therapeutic agents into the spinal region using a needle and syringe.Organ Size: The measurement of an organ in volume, mass, or heaviness.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.Chromatography, High Pressure Liquid: Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.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.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.Mice, Inbred ICRLung: Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.Rats, Inbred F344Analgesics, Opioid: Compounds with activity like OPIATE ALKALOIDS, acting at OPIOID RECEPTORS. Properties include induction of ANALGESIA or NARCOSIS.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.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.Heart Rate: The number of times the HEART VENTRICLES contract per unit of time, usually per minute.Pregnancy: The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.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.Motor Activity: The physical activity of a human or an animal as a behavioral phenomenon.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.Drug Combinations: Single preparations containing two or more active agents, for the purpose of their concurrent administration as a fixed dose mixture.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.Hemodynamics: The movement and the forces involved in the movement of the blood through the CARDIOVASCULAR SYSTEM.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.Drug Evaluation, Preclinical: Preclinical testing of drugs in experimental animals or in vitro for their biological and toxic effects and potential clinical applications.Analgesics: Compounds capable of relieving pain without the loss of CONSCIOUSNESS.Drug Therapy, Combination: Therapy with two or more separate preparations given for a combined effect.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.Injections, Intra-Arterial: Delivery of drugs into an artery.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.Spleen: An encapsulated lymphatic organ through which venous blood filters.Piperidines: A family of hexahydropyridines.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.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Intestinal Absorption: Uptake of substances through the lining of the INTESTINES.Blood Glucose: Glucose in blood.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.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.Drug Synergism: The action of a drug in promoting or enhancing the effectiveness of another drug.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.Naloxone: A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors.Eating: The consumption of edible substances.United StatesDopamine: 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.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.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.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.Absorption: The physical or physiological processes by which substances, tissue, cells, etc. take up or take in other substances or energy.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.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)Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Delayed-Action Preparations: Dosage forms of a drug that act over a period of time by controlled-release processes or technology.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).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.Pain: An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.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.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.Anti-Inflammatory Agents: Substances that reduce or suppress INFLAMMATION.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.Dexamethasone: An anti-inflammatory 9-fluoro-glucocorticoid.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.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.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.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.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.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.Animals, Newborn: Refers to animals in the period of time just after birth.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.Body Temperature: The measure of the level of heat of a human or animal.Models, Animal: Non-human animals, selected because of specific characteristics, for use in experimental research, teaching, or testing.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.Narcotic Antagonists: Agents inhibiting the effect of narcotics on the central nervous system.Kinetics: The rate dynamics in chemical or physical systems.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.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.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.Phytotherapy: Use of plants or herbs to treat diseases or to alleviate pain.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.Vasodilator Agents: Drugs used to cause dilation of the blood vessels.Pyridines: Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.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.Diabetes Mellitus, Experimental: Diabetes mellitus induced experimentally by administration of various diabetogenic agents or by PANCREATECTOMY.PiperazinesNeoplasms, Experimental: Experimentally induced new abnormal growth of TISSUES in animals to provide models for studying human neoplasms.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.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.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.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Neoplasm Transplantation: Experimental transplantation of neoplasms in laboratory animals for research purposes.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.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.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.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.Regional Blood Flow: The flow of BLOOD through or around an organ or region of the body.Methamphetamine: A central nervous system stimulant and sympathomimetic with actions and uses similar to DEXTROAMPHETAMINE. The smokable form is a drug of abuse and is referred to as crank, crystal, crystal meth, ice, and speed.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.Norepinephrine: 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.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.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.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.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)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).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.Chemistry, Pharmaceutical: Chemistry dealing with the composition and preparation of agents having PHARMACOLOGIC ACTIONS or diagnostic use.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).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.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.Ovariectomy: The surgical removal of one or both ovaries.Hyperalgesia: An increased sensation of pain or discomfort produced by mimimally noxious stimuli due to damage to soft tissue containing NOCICEPTORS or injury to a peripheral nerve.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.Mice, Inbred C3HLeukocyte 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.Hypnotics and Sedatives: Drugs used to induce drowsiness or sleep or to reduce psychological excitement or anxiety.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Analgesics, 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.Intestines: The section of the alimentary canal from the STOMACH to the ANAL CANAL. It includes the LARGE INTESTINE and SMALL INTESTINE.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)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.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).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.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.Brain Chemistry: Changes in the amounts of various chemicals (neurotransmitters, receptors, enzymes, and other metabolites) specific to the area of the central nervous system contained within the head. These are monitored over time, during sensory stimulation, or under different disease states.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.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.Hypothalamus: Ventral part of the DIENCEPHALON extending from the region of the OPTIC CHIASM to the caudal border of the MAMMILLARY BODIES and forming the inferior and lateral walls of the THIRD VENTRICLE.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.Substance Withdrawal Syndrome: Physiological and psychological symptoms associated with withdrawal from the use of a drug after prolonged administration or habituation. The concept includes withdrawal from smoking or drinking, as well as withdrawal from an administered drug.Adenoviridae: A family of non-enveloped viruses infecting mammals (MASTADENOVIRUS) and birds (AVIADENOVIRUS) or both (ATADENOVIRUS). Infections may be asymptomatic or result in a variety of diseases.Iodine Radioisotopes: Unstable isotopes of iodine that decay or disintegrate emitting radiation. I atoms with atomic weights 117-139, except I 127, are radioactive iodine isotopes.Edema: Abnormal fluid accumulation in TISSUES or body cavities. Most cases of edema are present under the SKIN in SUBCUTANEOUS TISSUE.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.Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.Nitric Oxide Synthase: An NADPH-dependent enzyme that catalyzes the conversion of L-ARGININE and OXYGEN to produce CITRULLINE and NITRIC OXIDE.Infusion Pumps, Implantable: Implanted fluid propulsion systems with self-contained power source for providing long-term controlled-rate delivery of drugs such as chemotherapeutic agents or analgesics. Delivery rate may be externally controlled or osmotically or peristatically controlled with the aid of transcutaneous monitoring.Chorionic Gonadotropin: A gonadotropic glycoprotein hormone produced primarily by the PLACENTA. Similar to the pituitary LUTEINIZING HORMONE in structure and function, chorionic gonadotropin is involved in maintaining the CORPUS LUTEUM during pregnancy. CG consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is virtually identical to the alpha subunits of the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity (CHORIONIC GONADOTROPIN, BETA SUBUNIT, HUMAN).Feces: Excrement from the INTESTINES, containing unabsorbed solids, waste products, secretions, and BACTERIA of the DIGESTIVE SYSTEM.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.Narcotics: Agents that induce NARCOSIS. Narcotics include agents that cause somnolence or induced sleep (STUPOR); natural or synthetic derivatives of OPIUM or MORPHINE or any substance that has such effects. They are potent inducers of ANALGESIA and OPIOID-RELATED DISORDERS.Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).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.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.Acute Disease: Disease having a short and relatively severe course.Hypoglycemic Agents: Substances which lower blood glucose levels.Rats, Inbred LewEndotoxins: Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells.Sheep: Any of the ruminant mammals with curved horns in the genus Ovis, family Bovidae. They possess lachrymal grooves and interdigital glands, which are absent in GOATS.Immunoglobulin G: The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.Myocardium: The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.Nicotine: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke.Sulfonamides: A group of compounds that contain the structure SO2NH2.Amphetamine: A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is DEXTROAMPHETAMINE.Injections, Intradermal: The forcing into the skin of liquid medication, nutrient, or other fluid through a hollow needle, piercing the top skin layer.Corpus Striatum: Striped GRAY MATTER and WHITE MATTER consisting of the NEOSTRIATUM and paleostriatum (GLOBUS PALLIDUS). It is located in front of and lateral to the THALAMUS in each cerebral hemisphere. The gray substance is made up of the CAUDATE NUCLEUS and the lentiform nucleus (the latter consisting of the GLOBUS PALLIDUS and PUTAMEN). The WHITE MATTER is the INTERNAL CAPSULE.Intestinal Mucosa: Lining of the INTESTINES, consisting of an inner EPITHELIUM, a middle LAMINA PROPRIA, and an outer MUSCULARIS MUCOSAE. In the SMALL INTESTINE, the mucosa is characterized by a series of folds and abundance of absorptive cells (ENTEROCYTES) with MICROVILLI.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.Intubation, Gastrointestinal: The insertion of a tube into the stomach, intestines, or other portion of the gastrointestinal tract to allow for the passage of food products, etc.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.
(1/1580) Transcutaneous immunization with bacterial ADP-ribosylating exotoxins as antigens and adjuvants.

Transcutaneous immunization (TCI) is a new technique that uses the application of vaccine antigens in a solution on the skin to induce potent antibody responses without systemic or local toxicity. We have previously shown that cholera toxin (CT), a potent adjuvant for oral and nasal immunization, can induce both serum and mucosal immunoglobulin G (IgG) and IgA and protect against toxin-mediated mucosal disease when administered by the transcutaneous route. Additionally, CT acts as an adjuvant for coadministered antigens such as tetanus and diphtheria toxoids when applied to the skin. CT, a member of the bacterial ADP-ribosylating exotoxin (bARE) family, is most potent as an adjuvant when the A-B subunits are present and functional. We now show that TCI induces secondary antibody responses to coadministered antigens as well as to CT in response to boosting immunizations. IgG antibodies to coadministered antigens were also found in the stools and lung washes of immunized mice, suggesting that TCI may target mucosal pathogens. Mice immunized by the transcutaneous route with tetanus fragment C and CT developed anti-tetanus toxoid antibodies and were protected against systemic tetanus toxin challenge. We also show that bAREs, similarly organized as A-B subunits, as well as the B subunit of CT alone, induced antibody responses to themselves when given via TCI. Thus, TCI appears to induce potent, protective immune responses to both systemic and mucosal challenge and offers significant potential practical advantages for vaccine delivery.  (+info)

(2/1580) A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation.

BACKGROUND AND METHODS: Use of nicotine-replacement therapies and the antidepressant bupropion helps people stop smoking. We conducted a double-blind, placebo-controlled comparison of sustained-release bupropion (244 subjects), a nicotine patch (244 subjects), bupropion and a nicotine patch (245 subjects), and placebo (160 subjects) for smoking cessation. Smokers with clinical depression were excluded. Treatment consisted of nine weeks of bupropion (150 mg a day for the first three days, and then 150 mg twice daily) or placebo, as well as eight weeks of nicotine-patch therapy (21 mg per day during weeks 2 through 7, 14 mg per day during week 8, and 7 mg per day during week 9) or placebo. The target day for quitting smoking was usually day 8. RESULTS: The abstinence rates at 12 months were 15.6 percent in the placebo group, as compared with 16.4 percent in the nicotine-patch group, 30.3 percent in the bupropion group (P<0.001), and 35.5 percent in the group given bupropion and the nicotine patch (P<0.001). By week 7, subjects in the placebo group had gained an average of 2.1 kg, as compared with a gain of 1.6 kg in the nicotine-patch group, a gain of 1.7 kg in the bupropion group, and a gain of 1.1 kg in the combined-treatment group (P<0.05). Weight gain at seven weeks was significantly less in the combined-treatment group than in the bupropion group and the placebo group (P<0.05 for both comparisons). A total of 311 subjects (34.8 percent) discontinued one or both medications. Seventy-nine subjects stopped treatment because of adverse events: 6 in the placebo group (3.8 percent), 16 in the nicotine-patch group (6.6 percent), 29 in the bupropion group (11.9 percent), and 28 in the combined-treatment group (11.4 percent). The most common adverse events were insomnia and headache. CONCLUSIONS: Treatment with sustained-release bupropion alone or in combination with a nicotine patch resulted in significantly higher long-term rates of smoking cessation than use of either the nicotine patch alone or placebo. Abstinence rates were higher with combination therapy than with bupropion alone, but the difference was not statistically significant.  (+info)

(3/1580) Extraction and analysis of cosmetic active ingredients from an anti-cellulitis transdermal delivery system by high-performance liquid chromatography.

A new transdermal delivery system that controls cellulitis is evaluated using reversed-phase high-performance liquid chromatography coupled with photodiode array detection. An extraction procedure and the validation of the analytical method to assay the active excipients from the Centella asiatica plant (asiaticoside, madacessic acid, and asiatic acid) are described. Excellent results ae obtained in terms of linearity, accuracy, and specificity of the analytical method.  (+info)

(4/1580) Higher dosage nicotine patches increase one-year smoking cessation rates: results from the European CEASE trial. Collaborative European Anti-Smoking Evaluation. European Respiratory Society.

The Collaborative European Anti-Smoking Evaluation (CEASE) was a European multicentre, randomized, double-blind placebo controlled smoking cessation study. The objectives were to determine whether higher dosage and longer duration of nicotine patch therapy would increase the success rate. Thirty-six chest clinics enrolled a total of 3,575 smokers. Subjects were allocated to one of five treatment arms: placebo and either standard or higher dose nicotine patches (15 mg and 25 mg daily) each given for 8 or 22 weeks with adjunctive moderately intensive support. The 12 month sustained success rates were: 25 mg patch for 22 weeks (L-25), 15.4%; 25 mg patch for 8 weeks (S-25), 15.9%; 15 mg patch for 22 weeks (L-15), 13.7%; 15 mg patch for 8 weeks (S-15), 11.7%; and placebo (P-0) 9.9% (placebo versus 15 mg, p<0.05; 25 mg versus 15 mg, p<0.03; 25 mg versus placebo, p<0.001, Chi-squared test). There was no significant difference in success rate between the two active treatment durations. Of the first week abstainers (n=1,698), 25.1% achieved success at 12 months as opposed to first week smokers, 2.7% of 1,877 subjects (p< 0.001). In summary, a higher than standard dose of nicotine patch was associated with an increase in the long-term success in smoking cessation but continuation of treatment beyond 8-12 weeks did not increase the success rates.  (+info)

(5/1580) Topical psoriasis therapy.

Psoriasis is a common dermatosis, affecting from 1 to 3 percent of the population. Until recently, the mainstays of topical therapy have been corticosteroids, tars, anthralins and keratolytics. Recently, however, vitamin D analogs, a new anthralin preparation and topical retinoids have expanded physicians' therapeutic armamentarium. These new topical therapies offer increased hope and convenience to the large patient population with psoriasis.  (+info)

(6/1580) A successful tobacco cessation program led by primary care nurses in a managed care setting.

We conducted a descriptive study of a tobacco cessation program sponsored by a health maintenance organization (HMO) and led by primary care nurses. The tobacco cessation program was conducted at 20 primary care clinics in northeastern and central Pennsylvania. We gauged the successfulness of the program by the patients' self-reported quit rates at 1 year. We also examined the association between quit rates and compliance with scheduled counseling visits, the impact of the availability of an HMO pharmacy benefit that supported the costs of nicotine replacement therapy, and the quit rates among patients with HMO insurance versus those with insurance other than managed care. Of 1,695 patients enrolled in the program from July 1993 to March 1996, 1,140 completed 1 year of follow-up. Of these, 348 (30.5%) reported they had quit using tobacco. Among the 810 HMO enrollees who participated in the program, the quit rate was 280 (34.6%); among the 330 non-HMO participants, the quit rate was 69 (20.9%), a statistically significant difference (P < 0.001). For all patients, keeping more than four visits with the program nurse was associated with a significantly higher likelihood of quitting (317/751 [42.2%] versus 32/389 [8.2%]; P < 0.001). Non-HMO patients were less likely than HMO enrollees to keep four or more visits (165 [50%] versus 586 [72.3%]; P < 0.001). We were unable to detect a difference in quit rates among those with and those without a pharmacy benefit (196/577 [34%] versus 84/233 [36.1%]). These data are limited by their descriptive nature and the lack of information about other factors important in determining the quit rate among program participants. Nevertheless, they suggest that HMOs can successfully sponsor nurse-led tobacco cessation programs in multiple primary care settings and achieve 1-year quit rates significantly higher than the 15% quit rate reported in the medical literature. In addition, successfully quitting tobacco use appeared to be associated with use of counseling visits but not with use of a pharmacy benefit to pay for nicotine replacement therapy. Even though tobacco cessation programs have the best chance of benefitting HMO enrollees, patients not enrolled in managed care plans also appear to benefit significantly. This finding has important implications for developing future strategies--including the role of managed care organizations, the need to defray the costs of nicotine replacement therapy, and the best approach to provide counseling to patients--to meet the Healthy People 2000 goal of reducing tobacco smoking.  (+info)

(7/1580) The effects of vapreotide, a somatostatin analogue, on gastric acidity, gallbladder emptying and hormone release after 1 week of continuous subcutaneous infusion in normal subjects.

AIMS: Somatostatin analogues (e.g. vapreotide) are used for treatment of acromegaly, endocrine tumours and variceal bleeding. The pharmacodynamic effects of vapreotide have, however, not been documented in the gastrointestinal tract. The aim of this study was to investigate the effects of continuous vapreotide administration on gastric acidity, gallbladder contraction and hormone release. METHODS: Ten healthy males participated in this randomised, placebo-controlled, double-blind, crossover trial. A constant vapreotide (or placebo) infusion (1.5 mg day(-1) s.c.) was given for 7 days with a portable pump. Intragastric pH was monitored on days 2 and 7. Gallbladder volume was sonographically assessed and the maximal ejection fraction was calculated. In addition basal and postprandial plasma levels of gastrin and cholecystokinin (CCK) were measured. RESULTS: After an initial increase in the median 24 h intragastric pH to a value of 2.6 on day 2, vapreotide's effect on pH decreased: (day 7: median pH=1.9; respective placebo values were 1.7 and 1.5). On the same days with vapreotide treatment, gallbladder contraction and plasma levels of CCK were reduced; maximal ejection fractions after meal stimulation were 18% and 20% (respective placebo values were 57% and 62%). Plasma gastrin levels were not changed with vapreotide treatment. CONCLUSIONS: The short lasting effect of vapreotide on intragastric acidity suggests a down-regulation of somatostatin receptors during treatment. The lack of effect on gastrin indicates that the effects on gastric pH are not mediated by gastrin. Constant vapreotide infusion (but not placebo) reduced gallbladder contraction suggesting a long-lasting effect on biliary function.  (+info)

(8/1580) Low dose subcutaneous adrenaline to prevent acute adverse reactions to antivenom serum in people bitten by snakes: randomised, placebo controlled trial.

OBJECTIVE: To assess the efficacy and safety of low dose adrenaline injected subcutaneously to prevent acute adverse reactions to polyspecific antivenom serum in patients admitted to hospital after snake bite. DESIGN: Prospective, double blind, randomised, placebo controlled trial. SETTING: District general hospital in Sri Lanka. SUBJECTS: 105 patients with signs of envenomation after snake bite, randomised to receive either adrenaline (cases) or placebo (controls) immediately before infusion of antivenom serum. INTERVENTIONS: Adrenaline 0.25 ml (1:1000). MAIN OUTCOME MEASURES: Development of acute adverse reactions to serum and side effects attributable to adrenaline. RESULTS: 56 patients (cases) received adrenaline and 49 (controls) received placebo as pretreatment. Six (11%) adrenaline patients and 21 (43%) control patients developed acute adverse reactions to antivenom serum (P=0.0002). Significant reductions in acute adverse reactions to serum were also seen in the adrenaline patients for each category of mild, moderate, and severe reactions. There were no significant adverse effects attributable to adrenaline. CONCLUSIONS: Use of 0.25 ml of 1:1000 adrenaline given subcutaneously immediately before administration of antivenom serum to patients with envenomation after snake bite reduces the incidence of acute adverse reactions to serum.  (+info)

*  Idrocilamide
Tissue and systemic diffusion of idrocilamide after cutaneous administration]". Revue du Rhumatisme (in French). 60 (12): 932-6 ...
*  Nystatin
On occasion, serum levels of the drug can be identified from oral, vaginal, or cutaneous administration, and lead to toxicity. ...
*  Photopheresis
... is currently standard therapy approved by the U.S. Food and Drug Administration (FDA) for cutaneous T-cell ... "Treatment of cutaneous T-cell lymphoma by extracorporeal photochemotherapy. Preliminary results". New England Journal of ...
*  Denileukin diftitox
In 1999 Ontak was approved by the U.S. Food and Drug Administration (FDA) for treatment of Cutaneous T-cell lymphoma (CTCL). ...
*  Interleukin 2
In 1999 Ontak was approved by the U.S. Food and Drug Administration (FDA) for treatment of Cutaneous T-cell Lymphoma (CTCL). IL ... It has been approved by the Food and Drug Administration (FDA) and in several European countries for the treatment of cancers ( ... Shaker MA, Younes HM (July 2009). "Interleukin-2: evaluation of routes of administration and current delivery systems in cancer ... Food and Drug Administration (FDA) refused to approve Cetus' application to market IL-2. The failure led to the collapse of ...
*  Chlormethine
... have been studies demonstrating that topical administration of mechlorethamine has efficacy in mycosis fungoides-type cutaneous ... Bunn Jr, P. A.; Hoffman, S. J.; Norris, D; Golitz, L. E.; Aeling, J. L. (1994). "Systemic therapy of cutaneous T-cell lymphomas ... Topical chemotherapy in cutaneous T-cell lymphoma: positive results of a randomized, controlled, multicenter trial testing the ...
*  Modafinil
... the US Food and Drug Administration received six cases of severe cutaneous adverse reactions associated with modafinil, ... In 1998, modafinil was approved by the U.S. Food and Drug Administration for the treatment of narcolepsy and in 2003 for shift ... "Prescription Drug Marketing Act of 1987 (PDMA), PL 100-293". U.S. Food and Drug Administration. Archived from the original on ... Cmax (peak levels) occurs approximately 2-3 hours after administration. Food slows absorption, but does not affect the total ...
*  Cutaneous leishmaniasis
In October 2006 it received orphan drug status from the US Food and Drug administration. The drug is generally better tolerated ... Cutaneous leishmaniasis has been seen in American and Canadian troops coming back from Afghanistan. The Middle East, in 2016, ... Cutaneous leishmaniasis (also known as oriental sore, tropical sore, chiclero ulcer, chiclero's ulcer or Aleppo boil) is the ... Besides humans, cutaneous leishmaniasis often affects other animals, notably in dogs as canine leishmaniasis. Calvopiña, M; ...
*  Terbinafine
The U.S. Food and Drug Administration has approved the first generic versions of prescription Lamisil (terbinafine ... Callen JP, Hughes AP, Kulp-Shorten C (September 2001). "Subacute cutaneous lupus erythematosus induced or exacerbated by ... Alternatives to by mouth administration have been studied. Terbinafine hydrochloride may induce or exacerbate subacute ... "PI and CMI Trade Names and Active Ingredients containing Terbinafine". Therapeutic Goods Administration. Australian Government ...
*  Exanthematic pustular psoriasis
It usually follows an infection or may occur as a result of administration of specific medications. Psoriasis List of cutaneous ... Exanthematic pustular psoriasis is a cutaneous condition characterized by an acute eruption of small pustules, abruptly ...
*  Melanin
With humans, exposure to sunlight stimulates the skin to produce vitamin D. Because high levels of cutaneous melanin act as a ... December 2012). "Comparison of oral and transdermal administration of rasagiline mesylate on human melanoma tumor growth in ... some to suggest that cutaneous melanin might somehow serve to protect the neuromelanin in substantia nigra from external toxins ... vivo". Cutaneous and Ocular Toxicology. 31 (4): 312-7. doi:10.3109/15569527.2012.676119. PMID 22515841. King G, Yerger VB, ...
*  Atracurium besilate
... the histamine release following administration of these agents is associated with observable cutaneous flushing (facial face ... Ortalli GL, Tiberio I, Mammana G (Mar 1993). "A case of severe bronchospasm and laryngospasm after atracurium administration". ... Uratsuji Y, Konishi M, Ikegaki N, Kitada H (Jan 1991). "Possible bronchospasm after administration of vecuronium". Masui. 40 (1 ... Takki S, Tammisto T (Apr 1971). "Severe bronchospasm and circulatory collapse following the administration of d-tubocurarine". ...
*  Erythema
... cutaneous radiation syndrome, mercury toxicity, blister agents, niacin administration, or waxing and tweezing of the hairs-any ... List of cutaneous conditions Mosby's Medical Dictionary (9th ed.). St. Louis, Missouri: Elsevier. 2013. ISBN 978-0-323-08541-0 ...
*  Ketoconazole
... and in a variety of formulations for topical administration, such as creams (used to treat tinea; cutaneous candidiasis, ... Recently, the administration of systemic ketoconazole to two pregnant women for treatment of Cushing's syndrome was reported to ... On July 2013, the U.S. Food and Drug Administration (FDA) issued a warning that taking ketoconazole orally can cause severe ... Ketoconazole is sold commercially as a tablet for oral administration (although this use has been discontinued in a number of ...
*  Vorinostat
... by Merck for the treatment of cutaneous manifestations in patients with cutaneous T cell lymphoma (CTCL) when the disease ... Vorinostat was the first histone deacetylase inhibitor approved by the U.S. Food and Drug Administration (FDA) for the ... Alam, M. S.; Getz, M.; Haldar, K. (2016). "Chronic administration of an HDAC inhibitor treats both neurological and systemic ... "ZOLINZA, Merck's Investigational Medicine for Advanced Cutaneous T-Cell Lymphoma (CTCL), To Receive Priority Review from U.S. ...
*  Cutaneous T cell lymphoma
Food and Drug Administration granted orphan drug designation for a topical treatment for pruritus in cutaneous T-cell lymphoma ... Cutaneous B-cell lymphoma List of cutaneous conditions "Cutaneous T-Cell Lymphoma: Practice Essentials, Background, ... Cutaneous T cell lymphoma (CTCL) is a class of non-Hodgkin lymphoma, which is a type of cancer of the immune system. Unlike ... Cutaneous T-cell lymphoma may be divided into the several subtypes. Mycosis fungoides is the most common form of CTCL and is ...
*  Chaetomium atrobrunneum
Co-administration of the antifungal drugs fluconazole (delivered topically) and itraconazole (delivered orally) have been ... "Clavispora lusitaniae and Chaetomium atrobrunneum as Rare Agents of Cutaneous Infection". Mycopathologia. 169: 373-380. doi: ... Infections due to this species have typically occurred following invasive procedures such as intravenous drug administration ... effective in the treatment of cutaneous disease. Skin infections are thought to result from direct contact with environmental ...
*  Steroid folliculitis
medicine portal List of cutaneous conditions Steroid acne Freedberg, et al. (2003). Fitzpatrick's Dermatology in General ... Steroid folliculitis occurs following administration of glucocorticoids or corticotropin. Other medications can also mimic ...
*  Interferon beta-1a
Skin reactions with interferon beta are more common with subcutaneous administration and vary greatly in their clinical ... and can cause skin reactions at the injection site that may include cutaneous necrosis. ...
*  Paromomycin
The route of administration is intramuscular injection and capsule. Paromomycin topical cream with or without gentamicin is an ... Paromomycin was demonstrated to be effective against cutaneous leishmaniasis in clinical studies in the USSR in the 1960s, and ... Neal RA, Murphy AG, Olliaro P, Croft SL (1994). "Aminosidine ointments for the treatment of experimental cutaneous ... 2013). "Topical Paromomycin with or without Gentamicin for Cutaneous Leishmaniasis". N. Engl. J. Med. 368 (6): 524-32. doi: ...
*  Indoor tanning
2012). "Cutaneous melanoma attributable to sunbed use: systematic review and meta-analysis". BMJ. 345: e4757. doi:10.1136/bmj. ... "The Risks of Tanning". U.S. Food and Drug Administration. 14 October 2015. Fatiha El Ghissassi, Robert Baan, Kurt Straif, et al ... 1040.20)", U.S. Food and Drug Administration, 1 April 2016. Federal Trade Commission v. Mercola, 1:16-cv-04282 (N.D. Ill. 13 ... According to the Food and Drug Administration in 2010, possibly using the Indoor Tanning Association as its source: "Each year ...
*  Carbamazepine
... is relatively slowly but well absorbed after oral administration. Its plasma half-life is about 30 hours when it ... Kaniwa, N; Saito, Y (June 2013). "Pharmacogenomics of severe cutaneous adverse reactions and drug-induced liver injury". ... such as the DRESS syndrome form of severe cutaneous reactions, to carbamazepine among Japanese, Chinese, Korean, and Europeans ...
*  Exotoxin
A recombinant diphtheria exotoxin has been approved by the FDA for treatment of cutaneous T-cell lymphoma, an immune system ... have entered clinical trials against tumor growth but have yet to be approved by Food and Drug Administration. ...
*  Stevens-Johnson syndrome
SJS and TEN most often begin between 4 and 28 days after culprit drug administration. A published algorithm (ALDEN) to assess ... All three are part of a spectrum of severe cutaneous reactions (SCAR) which affect skin and mucous membranes. The distinction ... Severe Cutaneous Adverse Reactions (2002). "Correlations between clinical patterns and causes of Erythema Multiforme Majus, ... US Food and Drug Administration. 24 October 2007. Archived from the original on 11 December 2013. Raksha MP, Marfatia YS; ...
*  Mycosis fungoides
Cutaneous T-cell lymphoma Pagetoid reticulosis Premycotic phase Sézary's disease Secondary cutaneous CD30+ large cell lymphoma ... In 2010, the U.S. Food and Drug Administration granted orphan drug designation for naloxone lotion, a topical opioid receptor ... DermAtlas 197 The Lymphoma Information Network - Cutaneous T-Cell Lymphomas Cutaneous Lymphoma Foundation (formerly MFF). ... a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European ...
*  Skin and skin structure infection
Food and Drug Administration has changed the terminology to "acute bacterial skin and skin structure infections" (ABSSSI). The ... Infectious Diseases Society of America (IDSA) has retained the term "skin and soft tissue infection". List of cutaneous ... Food and Drug Administration. October 2013. Retrieved 2014-11-23. Xia, Fan Di; Song, Philip; Joyce, Cara; Mostaghimi, Arash ( ...
Administration, Cutaneous | ISHAR Online  Administration, Cutaneous | ISHAR Online
The climacteric is not an illness, but the menopause is an event that troubles a woman's present life and puts her future life at risk. One would like to think that, for the woman of the new millennium, the menopause has simply become what it is: a feminine milestone that marks the transition and path to another period of life. She appears younger than her mother was at her age, she has given birth when she decided to, she has had the number of children she wanted, and her social and professional roles are well defined ...
more infohttp://isharonline.org/tags/administration-cutaneous
Cutaneous Atrophy Secondary to Intra-articular Corticosteroid Administration | Annals of Internal Medicine | American College...  Cutaneous Atrophy Secondary to Intra-articular Corticosteroid Administration | Annals of Internal Medicine | American College...
Cutaneous Atrophy Secondary to Intra-articular Corticosteroid Administration JAMES T. CASSIDY, M.D., F.A.C.P.; GILES G. BOLE, M ... Cutaneous Atrophy Secondary to Intra-articular Corticosteroid Administration. Ann Intern Med. ;65:1008-1018. doi: 10.7326/0003- ... This presentation reports the occurrence of severe cutaneous atrophy of delayed onset at the site of intra-articular injection ...
more infohttps://annals.org/aim/article-abstract/681045/cutaneous-atrophy-secondary-intra-articular-corticosteroid-administration
Topical Administration of Manuka Oil Prevents UV-B Irradiation-Induced Cutaneous Photoaging in Mice  Topical Administration of Manuka Oil Prevents UV-B Irradiation-Induced Cutaneous Photoaging in Mice
... Oh Sook Kwon,1 Seung Hee ... S. R. Pinnell, "Cutaneous photodamage, oxidative stress, and topical antioxidant protection," Journal of the American Academy ... β-carotene in cutaneous photoprotection," Free Radical Biology and Medicine, vol. 25, no. 7, pp. 848-873, 1998. View at ...
more infohttps://www.hindawi.com/journals/ecam/2013/930857/ref/
Publications | AIDS Clinical Trials Group  Publications | AIDS Clinical Trials Group
Administration, Cutaneous. Evans SR, Yeh T-min, Sacktor N, et al. "Selegiline transdermal system (STS) for HIV-associated ... Administration, Oral. Sacktor N, Miyahara S, Evans S, et al. "Impact of minocycline on cerebrospinal fluid markers of oxidative ...
more infohttps://actgnetwork.org/pubmed_publications?page=4&s=keyword&o=asc
Effective Administration of Rituximab in Anti-MDA5 Antibody-Positive Dermatomyositis with Rapidly Progressive Interstitial Lung...  Effective Administration of Rituximab in Anti-MDA5 Antibody-Positive Dermatomyositis with Rapidly Progressive Interstitial Lung...
... his respiratory insufficiency and cutaneous involvement progressively worsened. However, the administration of rituximab (RTX) ... Effective Administration of Rituximab in Anti-MDA5 Antibody-Positive Dermatomyositis with Rapidly Progressive Interstitial Lung ... and refractory cutaneous involvement together with high levels of anti-melanoma differentiation-associated gene 5 antibody ( ... Disease and Refractory Cutaneous Involvement: A Case Report and Literature Review. Yuka Ogawa,1 Dai Kishida,1 Yasuhiro ...
more infohttps://www.hindawi.com/journals/crirh/2017/5386797/abs/
Patent US5511726 - Nebulizer device - Google Patents  Patent US5511726 - Nebulizer device - Google Patents
Cutaneous administration system. US6796303 *. 3 Jun 2002. 28 Sep 2004. Battelle Pulmonary Therapeutics, Inc.. Pulmonary aerosol ... Cutaneous administration system. US20040184999 *. 29 Jan 2004. 23 Sep 2004. Alexza Molecular Delivery Corporation. Delivery of ... Cutaneous administration system. US7550133. 20 Nov 2003. 23 Jun 2009. Alexza Pharmaceuticals, Inc.. Respiratory drug ...
more infohttp://www.google.ca/patents/US5511726
Povidone-iodine Against Sodium Hypochlorite as Skin Antiseptics - Full Text View - ClinicalTrials.gov  Povidone-iodine Against Sodium Hypochlorite as Skin Antiseptics - Full Text View - ClinicalTrials.gov
Administration, cutaneous. Iodophors. Chlorine compounds. Anti-infecting agents, local. Additional relevant MeSH terms: ...
more infohttps://clinicaltrials.gov/show/NCT00738543
A Smoking Cessation Trial in HIV-infected Patients in South Africa - Full Text View - ClinicalTrials.gov  A Smoking Cessation Trial in HIV-infected Patients in South Africa - Full Text View - ClinicalTrials.gov
administration, cutaneous. Additional relevant MeSH terms: Nicotine. Ganglionic Stimulants. Autonomic Agents. Peripheral ...
more infohttps://clinicaltrials.gov/ct2/show/study/NCT01484340?view=results
Novel approach to improve permeation of ondansetron across shed snake skin as a model membrane.  Novel approach to improve permeation of ondansetron across shed snake skin as a model membrane.
Administration, Cutaneous. Animals. Ethanol / pharmacology. Humans. Models, Animal. Molting*. Oleic Acid / pharmacology. ...
more infohttp://www.biomedsearch.com/nih/Novel-approach-to-improve-permeation/11428654.html
Study on dermatoses and their prevalence in groups of confirmed alcoholic individuals in comparison to a non-alcoholic group of...  Study on dermatoses and their prevalence in groups of confirmed alcoholic individuals in comparison to a non-alcoholic group of...
Key words: Administration, cutaneous; Alcoholism; Skin manifestations; Substance withdrawal syndrome. RESUMO. FUNDAMENTOS:. A ... The cutaneous signs that denote alcohol consumption abuse are widely known. They include jaundice, facial flushing, spider ... Cutaneous changes in chronic alcoholics. Indian J Dermatol Venerol Leprol. 2004;70:79-81. [ Links ] ... Thus, the present survey of cutaneous lesions found in a population of confirmed alcoholic patients that have been hospitalized ...
more infohttp://www.scielo.br/scielo.php?script=sci_arttext&pid=S0365-05962013000300368
Upregulation of inducible nitric oxide synthase contributes to attenuated cutaneous vasodilation in essential hypertensive...  Upregulation of inducible nitric oxide synthase contributes to attenuated cutaneous vasodilation in essential hypertensive...
Administration, Cutaneous. Analysis of Variance. Blotting, Western. Case-Control Studies. Dose-Response Relationship, Drug. ... cutaneous vascular conductance; P,0.05) and neuronal NO synthase-inhibited sites (94±4% versus 77±3% cutaneous vascular ... iNOS inhibition augmented the NO-dependent local heating response (93±2% versus 89±10% cutaneous vascular conductance). ... Upregulation of inducible nitric oxide synthase contributes to attenuated cutaneous vasodilation in essential hypertensive ...
more infohttp://www.biomedsearch.com/nih/Upregulation-Inducible-Nitric-Oxide-Synthase/21931069.html
Severe Cutaneous and Neurologic Toxicity in Melanoma Patients during Vemurafenib Administration Following Anti-PD-1 Therapy |...  Severe Cutaneous and Neurologic Toxicity in Melanoma Patients during Vemurafenib Administration Following Anti-PD-1 Therapy |...
Severe Cutaneous and Neurologic Toxicity in Melanoma Patients during Vemurafenib Administration Following Anti-PD-1 Therapy. ... Severe Cutaneous and Neurologic Toxicity in Melanoma Patients during Vemurafenib Administration Following Anti-PD-1 Therapy ... Severe Cutaneous and Neurologic Toxicity in Melanoma Patients during Vemurafenib Administration Following Anti-PD-1 Therapy ... Severe Cutaneous and Neurologic Toxicity in Melanoma Patients during Vemurafenib Administration Following Anti-PD-1 Therapy ...
more infohttp://cancerimmunolres.aacrjournals.org/content/early/2013/10/22/2326-6066.CIR-13-0092
Panobinostat/Bortezomib/Dexamethasone in Relapsed or Relapsed-and-refractory Multiple Myeloma - Full Text View - ClinicalTrials...  Panobinostat/Bortezomib/Dexamethasone in Relapsed or Relapsed-and-refractory Multiple Myeloma - Full Text View - ClinicalTrials...
1.3mg/m2 sub-cutaneous administration; Cycle 1-4: 2 weeks on/1 week off twice a week for patients ,=75 years at time of ... 1.3mg/m2 sub-cutaneous administration; Cycle 1-4: 2 weeks on/1 week off twice a week for patients ,=75 years at time of ... 1.3mg/m2 sub-cutaneous administration; Cycle 1-4: 2 weeks on/1 week off twice a week for patients ,=75 years at time of ... pre and 24h after BTZ administration; patients ,= 75 years at time of screening: 20mg/dose patients , 75 years: 10mg/dose ...
more infohttps://www.clinicaltrials.gov/ct2/show/study/NCT02654990?recrs=a&cond=Multiple+Myeloma&cntry=ES&map_cntry=ES&draw=1&show_locs=Y
EPO - T 1164/11 () of 18.2.2015  EPO - T 1164/11 () of 18.2.2015
Medical apparatus for cutaneous administration of mendicaments. Applicant name:. C.I.R.C.E S.R.L.. ... which gave the energy to penetrate the cutaneous barrier and deliver the active principle to the target area, was rubbed on the ...
more infohttp://www.epo.org/law-practice/case-law-appeals/recent/t111164eu1.html
Advantage 100 Medium 🐶 Dogs 4-10kg  Advantage 100 Medium 🐶 Dogs 4-10kg
The solution is indicated for cutaneous administration. Following topical application, the product is quickly distributed over ... Figure 3: Administration to dogs up to 25kg. For dogs of 25 kg body weight and greater. The dog should be standing for easy ... Figure 4: Administration to dogs over 25kg. For all dogs. Do not apply an excessive amount of solution at any one spot that ... Figure 2: Administration to the cat/rabbit. For dogs of less than 25kg body weight. With the dog in the standing position, part ...
more infohttps://www.viovet.co.uk/Advantage-100-Medium-Dogs-4-10kg/c41750/?sct_t=1544142633&sct_q=advantage&sct_r=4
Advantage 80 Large 🐱 Cats & Pet 🐰 Rabbits  Advantage 80 Large 🐱 Cats & Pet 🐰 Rabbits
The solution is indicated for cutaneous administration. Following topical application, the product is quickly distributed over ... Figure 3: Administration to dogs up to 25kg. For dogs of 25 kg body weight and greater. The dog should be standing for easy ... Figure 4: Administration to dogs over 25kg. For all dogs. Do not apply an excessive amount of solution at any one spot that ... Figure 2: Administration to the cat/rabbit. For dogs of less than 25kg body weight. With the dog in the standing position, part ...
more infohttps://www.viovet.co.uk/Advantage-80-Large-Cats-Pet-Rabbits/c41744/?sct_t=1549967777&sct_q=advantage&sct_r=2
763. Cyfluthrin (Pesticide residues in food: 1987 evaluations Part II Toxicology)  763. Cyfluthrin (Pesticide residues in food: 1987 evaluations Part II Toxicology)
Neurotoxicity study on chickens after cutaneous administration (cumulation tests). Unpublished report no. 10768 from Bayer ... About 5% was retained after i.v. administration, and about 0.5% was retained after intraduodenal administration. The study ... After i.v. administration, the plasma half-life [t(1/2)] of elimination was found to be biphasic, with a t(1/2) for the rapid ... A single oral administration of 0.5 or 10 mg/kg had little effect on elimination. The t(1/2) of absorption was calculated to be ...
more infohttp://www.inchem.org/documents/jmpr/jmpmono/v87pr08.htm
  • We describe the case of a 48-year-old man with dermatomyositis (DM) who demonstrated rapidly progressive interstitial lung disease (RP-ILD) and refractory cutaneous involvement together with high levels of anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5-Ab). (hindawi.com)
  • Mutations in the NF1 tumor suppressor gene cause neurofibromatosis type I (NF1), a disease characterized by the formation of cutaneous neurofibromas infiltrated with a high density of degranulating mast cells. (rupress.org)
  • Outside of positive genetic testing confirming a pathological TSC1 or TSC2 mutation, the clinical diagnosis of TSC relies on a combination of identifiable major and minor characteristics, with cutaneous findings composing a large part of both major (hypomelanotic macules, angiofibromas, ungual fibromas, shagreen patch) and minor ('confetti' skin lesions) features ( table 1 ). (bmj.com)
  • The cutaneous mycoses are superficial fungal infections of the skin, hair or nails. (nps.org.au)
  • Our results indicate that anandamide excited cutaneous C nociceptors and produced nocifensive behaviors via activation of TRPV1 receptors. (umn.edu)
  • Cutaneous fungal infections are usually treated topically, but nail and hair infections, widespread dermatophytosis and chronic non-responsive yeast infections are best treated with oral antifungal drugs. (nps.org.au)