Tetrahydronaphthalenes: Partially saturated 1,2,3,4-tetrahydronaphthalene compounds.Research Report: Detailed account or statement or formal record of data resulting from empirical inquiry.Databases, Protein: Databases containing information about PROTEINS such as AMINO ACID SEQUENCE; PROTEIN CONFORMATION; and other properties.Internet: A loose confederation of computer communication networks around the world. The networks that make up the Internet are connected through several backbone networks. The Internet grew out of the US Government ARPAnet project and was designed to facilitate information exchange.User-Computer Interface: The portion of an interactive computer program that issues messages to and receives commands from a user.Software: Sequential operating programs and data which instruct the functioning of a digital computer.Venous Pressure: The blood pressure in the VEINS. It is usually measured to assess the filling PRESSURE to the HEART VENTRICLE.ArchivesPolyethylene Terephthalates: Polyester polymers formed from terephthalic acid or its esters and ethylene glycol. They can be formed into tapes, films or pulled into fibers that are pressed into meshes or woven into fabrics.DelawareTextilesPolyesters: Polymers of organic acids and alcohols, with ester linkages--usually polyethylene terephthalate; can be cured into hard plastic, films or tapes, or fibers which can be woven into fabrics, meshes or velours.Second-Look Surgery: A followup operation to examine the outcome of the previous surgery and other treatments, such as chemotherapy or radiation therapy.Phthalic Acids: A group of compounds that has the general structure of a dicarboxylic acid-substituted benzene ring. The ortho-isomer is used in dye manufacture. (Dorland, 28th ed)Textile Industry: The aggregate business enterprise of manufacturing textiles. (From Random House Unabridged Dictionary, 2d ed)Acetogenins: Polyketides of up to a few dozen carbons in length, formed by chain extension of multiple PROPIONATES and oxygenated to form tetrahydrofuran and lactone rings along the length of the chain. They are found in ANNONACEAE and other PLANTS. Related compounds cyclize to MACROLIDES.Annonaceae: The custard-apple plant family of the order Magnoliales, subclass Magnoliidae, class Magnoliopsida. Some members provide large pulpy fruits and commercial timber. Leaves and wood are often fragrant. Leaves are simple, with smooth margins, and alternately arranged in two rows along the stems.Famous PersonsAnnona: A plant genus of the family ANNONACEAE. It has edible fruit and seeds which contain acetogenins and benzoquinazoline and other alkaloids.North CarolinaBenzethonium: Bactericidal cationic quaternary ammonium surfactant used as a topical anti-infective agent. It is an ingredient in medicaments, deodorants, mouthwashes, etc., and is used to disinfect apparatus, etc., in the food processing and pharmaceutical industries, in surgery, and also as a preservative. The compound is toxic orally as a result of neuromuscular blockade.Furans: Compounds with a 5-membered ring of four carbons and an oxygen. They are aromatic heterocycles. The reduced form is tetrahydrofuran.Mustelidae: A family of terrestrial carnivores with long, slender bodies, long tails, and anal scent glands. They include badgers, weasels, martens, FERRETS; MINKS; wolverines, polecats, and OTTERS.Wolves: Any of several large carnivorous mammals of the family CANIDAE that usually hunt in packs.Portraits as Topic: Graphic representations, especially of the face, of real persons, usually posed, living or dead. (From Thesaurus for Graphic Materials II, p540, 1995)Saint Lucia: An independent state in the West Indies. Its capital is Castries. It was probably discovered by Columbus in 1502 and first settled by the English in 1605. Contended for by the French and English in the 17th century, it was regarded as neutral in 1748 but changed hands many times in the wars of the 19th century. It became a self-governing state in association with Great Britain in 1967 and achieved independence in 1979. Columbus named it for the day on which he discovered it, the feast of St. Lucy, a Sicilian virgin martyr. (From Webster's New Geographical Dictionary, 1988, p1051 & Room, Brewer's Dictionary of Names, 1992, p477)Teratology: A branch of embryology for the study of congenital malformations and developmental abnormalities.Desulfovibrio: A genus of gram-negative, anaerobic, rod-shaped bacteria capable of reducing sulfur compounds to hydrogen sulfide. Organisms are isolated from anaerobic mud of fresh and salt water, animal intestines, manure, and feces.History, 20th Century: Time period from 1901 through 2000 of the common era.Butylated Hydroxytoluene: A di-tert-butyl PHENOL with antioxidant properties.Butylated Hydroxyanisole: Mixture of 2- and 3-tert-butyl-4-methoxyphenols that is used as an antioxidant in foods, cosmetics, and pharmaceuticals.Pantothenic Acid: A butyryl-beta-alanine that can also be viewed as pantoic acid complexed with BETA ALANINE. It is incorporated into COENZYME A and protects cells against peroxidative damage by increasing the level of GLUTATHIONE.Silicone Elastomers: Polymers of silicone that are formed by crosslinking and treatment with amorphous silica to increase strength. They have properties similar to vulcanized natural rubber, in that they stretch under tension, retract rapidly, and fully recover to their original dimensions upon release. They are used in the encapsulation of surgical membranes and implants.Hair: A filament-like structure consisting of a shaft which projects to the surface of the SKIN from a root which is softer than the shaft and lodges in the cavity of a HAIR FOLLICLE. It is found on most surfaces of the body.Elastomers: A generic term for all substances having the properties of stretching under tension, high tensile strength, retracting rapidly, and recovering their original dimensions fully. They are generally POLYMERS.Hair Follicle: A tube-like invagination of the EPIDERMIS from which the hair shaft develops and into which SEBACEOUS GLANDS open. The hair follicle is lined by a cellular inner and outer root sheath of epidermal origin and is invested with a fibrous sheath derived from the dermis. (Stedman, 26th ed) Follicles of very long hairs extend into the subcutaneous layer of tissue under the SKIN.Bibliometrics: The use of statistical methods in the analysis of a body of literature to reveal the historical development of subject fields and patterns of authorship, publication, and use. Formerly called statistical bibliography. (from The ALA Glossary of Library and Information Science, 1983)DenmarkIllinoisPublications: Copies of a work or document distributed to the public by sale, rental, lease, or lending. (From ALA Glossary of Library and Information Science, 1983, p181)Petasites: A plant genus of the family ASTERACEAE. Members contain SESQUITERPENES. The common name of sweet coltsfoot is similar to the common name for TUSSILAGO.Research: Critical and exhaustive investigation or experimentation, having for its aim the discovery of new facts and their correct interpretation, the revision of accepted conclusions, theories, or laws in the light of newly discovered facts, or the practical application of such new or revised conclusions, theories, or laws. (Webster, 3d ed)Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing.Fenclonine: A selective and irreversible inhibitor of tryptophan hydroxylase, a rate-limiting enzyme in the biosynthesis of serotonin (5-HYDROXYTRYPTAMINE). Fenclonine acts pharmacologically to deplete endogenous levels of serotonin.Fear: The affective response to an actual current external danger which subsides with the elimination of the threatening condition.Amphetamines: Analogs or derivatives of AMPHETAMINE. Many are sympathomimetics and central nervous system stimulators causing excitation, vasopressin, bronchodilation, and to varying degrees, anorexia, analepsis, nasal decongestion, and some smooth muscle relaxation.Ketanserin: A selective serotonin receptor antagonist with weak adrenergic receptor blocking properties. The drug is effective in lowering blood pressure in essential hypertension. It also inhibits platelet aggregation. It is well tolerated and is particularly effective in older patients.Receptor, Serotonin, 5-HT2A: A serotonin receptor subtype found widely distributed in peripheral tissues where it mediates the contractile responses of variety of tissues that contain SMOOTH MUSCLE. Selective 5-HT2A receptor antagonists include KETANSERIN. The 5-HT2A subtype is also located in BASAL GANGLIA and CEREBRAL CORTEX of the BRAIN where it mediates the effects of HALLUCINOGENS such as LSD.Serotonin Antagonists: Drugs that bind to but do not activate serotonin receptors, thereby blocking the actions of serotonin or SEROTONIN RECEPTOR AGONISTS.Receptor, Serotonin, 5-HT2C: A serotonin receptor subtype found primarily in the CENTRAL NERVOUS SYSTEM and the CHOROID PLEXUS. This receptor subtype is believed to mediate the anorectic action of SEROTONIN, while selective antagonists of the 5-HT2C receptor appear to induce ANXIETY. Several isoforms of this receptor subtype exist, due to adenine deaminase editing of the receptor mRNA.Hepatomegaly: Enlargement of the liver.Cachexia: General ill health, malnutrition, and weight loss, usually associated with chronic disease.Periodicals as Topic: A publication issued at stated, more or less regular, intervals.PubMed: A bibliographic database that includes MEDLINE as its primary subset. It is produced by the National Center for Biotechnology Information (NCBI), part of the NATIONAL LIBRARY OF MEDICINE. PubMed, which is searchable through NLM's Web site, also includes access to additional citations to selected life sciences journals not in MEDLINE, and links to other resources such as the full-text of articles at participating publishers' Web sites, NCBI's molecular biology databases, and PubMed Central.Books

Mibefradil (Ro 40-5967) inhibits several Ca2+ and K+ currents in human fusion-competent myoblasts. (1/606)

1. The effect of mibefradil (Ro 40-5967), an inhibitor of T-type Ca2+ current (I(Ca)(T)), on myoblast fusion and on several voltage-gated currents expressed by fusion-competent myoblasts was examined. 2. At a concentration of 5 microM, mibefradil decreases myoblast fusion by 57%. At this concentration, the peak amplitudes of I(Ca)(T) and L-type Ca2+ current (I(Ca)(L)) measured in fusion-competent myoblasts are reduced by 95 and 80%, respectively. The IC50 of mibefradil for I(Ca)(T) and I(Ca)(L) are 0.7 and 2 microM, respectively. 3. At low concentrations, mibefradil increased the amplitude of I(Ca)(L) with respect to control. 4. Mibefradil blocked three voltage-gated K+ currents expressed by human fusion-competent myoblasts: a delayed rectifier K+ current, an ether-a-go-go K+ current, and an inward rectifier K+ current, with a respective IC50 of 0.3, 0.7 and 5.6 microM. 5. It is concluded that mibefradil can interfere with myoblast fusion, a mechanism fundamental to muscle growth and repair, and that the interpretation of the effect of mibefradil in a given system should take into account the action of this drug on ionic currents other than Ca2+ currents.  (+info)

Developmental regulation of expression of the D3 dopamine receptor in rat nucleus accumbens and islands of Calleja. (2/606)

The dopamine D3 receptor (D3R) belongs to the D2 subfamily and is expressed in the rat brain in targets of the mesolimbic dopaminergic system. Little is known about its normal development and control by dopaminergic innervation. We studied developmental expression of D3R in the rat nucleus accumbens (NAC) and islands of Calleja (ISC). At postnatal day (P) 7, D3 binding sites and mRNA were low in both areas. By P14, D3R and mRNA concentrations were close to adult levels in the ISC, whereas, in the NAC, binding increased until 3 months after birth. Cellular concentrations of D3 mRNA in the ISC increased with age in conjunction with a decrease in the number of D3 positive cells. In the NAC, the number of positive cells increased, whereas cellular levels of expression remained unchanged. Neonatal 6-hydroxydopamine lesion caused age-dependent changes in D3R expression. D3 binding sites did not change at P7 or P14, but there was a reduction in the number of D3 mRNA positive neurons accompanied by an increase in cellular levels of D3 mRNA at P14, suggesting that changes occurred in a subset of neurons. Up-regulation of D3 binding sites in NAC and ISC occurred 1 month after the lesion (P35) concomitant with a decrease in cellular levels of D3 mRNA and the number of D3 mRNA positive cells. At 3 months (P90) after the lesion, an increase in D3 mRNA occurred with no change in D3 binding sites. D3R shows region-specific dynamics in receptor/mRNA expression during development and is sensitive to loss of dopamine in early postnatal development.  (+info)

Genetic analysis of biodegradation of tetralin by a Sphingomonas strain. (3/606)

A strain designated TFA which very efficiently utilizes tetralin has been isolated from the Rhine river. The strain has been identified as Sphingomonas macrogoltabidus, based on 16S rDNA sequence similarity. Genetic analysis of tetralin biodegradation has been performed by insertion mutagenesis and by physical analysis and analysis of complementation between the mutants. The genes involved in tetralin utilization are clustered in a region of 9 kb, comprising at least five genes grouped in two divergently transcribed operons.  (+info)

Central hypothyroidism associated with retinoid X receptor-selective ligands. (4/606)

BACKGROUND: The occurrence of symptomatic central hypothyroidism (characterized by low serum thyrotropin and thyroxine concentrations) in a patient with cutaneous T-cell lymphoma during therapy with the retinoid X receptor-selective ligand bexarotene led us to hypothesize that such ligands could reversibly suppress thyrotropin production by a thyroid hormone-independent mechanism and thus cause central hypothyroidism. METHODS: We evaluated thyroid function in 27 patients with cutaneous T-cell lymphoma who were enrolled in trials of high-dose oral bexarotene at one institution. In addition, we evaluated the in vitro effect of triiodothyronine, 9-cis-retinoic acid, and the retinoid X receptor-selective ligand LGD346 on the activity of the thyrotropin beta-subunit gene promoter. RESULTS: The mean serum thyrotropin concentration declined from 2.2 mU per liter at base line to 0.05 mU per liter during treatment with bexarotene (P<0.001), and the mean serum free thyroxine concentration declined from 1.0 ng per deciliter (12.9 pmol per liter) at base line to 0.45 ng per deciliter (5.8 pmol per liter) (P<0.001) during treatment. The degree of suppression of thyrotropin secretion tended to be greater in patients treated with higher doses of bexarotene (>300 mg per square meter of body-surface area per day) and in those with a history of treatment with interferon alfa. Nineteen patients had symptoms or signs of hypothyroidism, particularly fatigue and cold intolerance. The symptoms improved after the initiation of thyroxine therapy, and all patients became euthyroid after treatment with bexarotene was stopped. In vitro, LGD346 suppressed the activity of the thyrotropin beta-subunit gene promoter in thyrotrophs by as much as 50 percent, an effect similar to that of triiodothyronine and 9-cis-retinoic acid. CONCLUSIONS: Hypothyroidism may develop in patients with cutaneous T-cell lymphoma who are treated with high-dose bexarotene, most likely because the retinoid X receptor-selective ligand suppresses thyrotropin secretion.  (+info)

Estradiol modulates vascular response to melatonin in rat caudal artery. (5/606)

The purpose of this study was to determine whether estrogen modulates the function of vascular melatonin receptors. We used the rat caudal artery and found that the contractile effects of melatonin were influenced by the estrous cycle, ovariectomy, and estrogen replacement. In arterial ring segments isolated from female rats, melatonin potentiated, in a concentration-dependent manner, contractions produced either by adrenergic nerve stimulation or by phenylephrine. Constrictor responses to melatonin were smaller in arteries from female rats in proestrus compared with other stages of the estrous cycle and after ovariectomy. Administration of 17beta-estradiol to ovariectomized female rats also resulted in decreased constriction of isolated arteries to melatonin; however, in vitro addition of 17beta-estradiol (10(-7) M) had no effect. In the caudal artery, melatonin appears to act on two receptor subtypes that mediate contraction and relaxation, respectively. The selective melatonin MT2-receptor antagonist 4-phenyl-2-propionamidotetraline (4P-PDOT) enhanced constrictor responses to melatonin in arterial segments from intact female rats, consistent with the inhibition of MT2 receptor-mediated relaxation. In contrast, 4P-PDOT had no significant effect in arteries from ovariectomized female rats. However, when estradiol was replaced in vivo, the effect of 4P-PDOT on melatonin responses was restored. Thus circulating estradiol appears to enhance MT2 melatonin-receptor function in the thermoregulatory caudal artery of the female rat resulting in increased vasodilatation in response to melatonin.  (+info)

Metabolic interactions between mibefradil and HMG-CoA reductase inhibitors: an in vitro investigation with human liver preparations. (6/606)

AIMS: To determine the effects of mibefradil on the nletabolism in human liver microsomal preparations of the HMG-CoA reductase inhibitors simvastatin, lovastatin, atorvastatin, cerivastatin and fluvastatin. METHODS: Metabolism of the above five statins (0.5, 5 or 10 microM), as well as of specific CYP3A4/5 and CYP2C8/9 marker substrates, was examined in human liver microsomal preparations in the presence and absence of mibefradil (0.1-50 microM). RESULTS: Mibefradil inhibited, in a concentration-dependent fashion, the metabolism of the four statins (simvastatin, lovastatin, atorvastatin and cerivastatin) known to be substrates for CYP3A. The potency of inhibition was such that the IC50 values (<1 microM) for inhibition of all of the CYP3A substrates fell within the therapeutic plasma concentrations of mibefradil, and was comparable with that of ketoconazole. However, the inhibition by mibefradil, unlike that of ketoconazole, was at least in part mechanism-based. Based on the kinetics of its inhibition of hepatic testosterone 6beta-hydroxylase activity, mibefradil was judged to be a powerful mechanism-based inhibitor of CYP3A4/5, with values for Kinactivation, Ki and partition ratio (moles of mibefradil metabolized per moles of enzyme inactivated) of 0.4 min(-1), 2.3 microM and 1.7, respectively. In contrast to the results with substrates of CYP3A, metabolism of fluvastatin, a substrate of CYP2C8/9, and the hydroxylation of tolbutamide, a functional probe for CYP2C8/9, were not inhibited by mibefradil. CONCLUSION: Mibefradil, at therapeutically relevant concentrations, strongly suppressed the metabolism in human liver microsomes of simvastatin, lovastatin, atorvastatin and cerivastatin through its inhibitory effects on CYP3A4/5, while the effects of mibefradil on fluvastatin, a substrate for CYP2C8/9, were minimal in this system. Since mibefradil is a potent mechanism-based inhibitor of CYP3A4/5, it is anticipated that clinically significant drug-drug interactions will likely ensue when mibefradil is coadministered with agents which are cleared primarily by CYP3A-mediated pathways.  (+info)

Morphological transformation induced by activation of the mitogen-activated protein kinase pathway requires suppression of the T-type Ca2+ channel. (7/606)

Transformation of fibroblasts by various oncogenes, including ras, mos, and src accompanies with characteristic morphological changes from flat to round (or spindle) shapes. Such morphological change is believed to play an important role in establishing malignant characteristics of cancer cells. Activation of the mitogen-activated protein kinase (MAPK) pathway is a converging downstream event of transforming activities of many oncogene products commonly found in human cancers. Intracellular calcium is known to regulate cellular morphology. In fibroblasts, Ca2+ influx is primarily controlled by two types of Ca2+ channels (T- and L-types). Here, we report that the T-type current was specifically inhibited in cells expressing oncogenically activated Ras as well as gain-of-function mutant MEK (MAPK/extracellular signal-regulated kinase (ERK) kinase, a direct activator of MAPK), whereas treatment of ras-transformed cells with a MEK-specific inhibitor restored T-type Ca2+ channel activity. Using a T-type Ca2+ channel antagonist, we further found that suppression of the T-type Ca2+ channel by the activated MAPK pathway is a prerequisite event for the induction and/or maintenance of transformation-associated morphological changes.  (+info)

Combination of calcium channel blockers and beta-adrenoceptor blockers for patients with exercise-induced angina pectoris: a double-blind parallel-group comparison of different classes of calcium channel blockers. Netherlands Working Group on Cardiovascular Research (WCN). (8/606)

AIMS: The combination of calcium channel blockers and beta-adrenoceptor blockers is more effective for the treatment of exercise-induced angina pectoris than beta-adrenoceptor blocker monotherapy. As ischaemia in exercise-induced angina is preceded by increase in heart rate, calcium channel blockers with negative chronotropic properties may perform better for this purpose than nonchronotropic compounds. METHODS: A 335 patient double-blind parallel-group study comparing 14 day treatment with amlodipine 5 and 10 mg, with diltiazem 200 and 300 mg, and mibefradil 50 and 100 mg added to baseline beta-adrenoceptor blocker treatment was performed. Exercise testing (ETT) was performed by bicycle ergometry. RESULTS: Although none of the calcium channel blockers improved duration of exercise or amount of workload, all significantly delayed onset of 1 mm ST-segment depression on ETT (P<0.001 for any treatment vs baseline). In addition, mibefradil, both low and high dose treatment, produced the longest delays (low dose: different from diltiazem and amlodipine by 24.1 and 29.8 s, respectively, P<0. 003 and <0.001; high dose: different from diltiazem and amlodipine by 33.7 and 37.0 s, respectively, P<0.001 and <0.001). These effects were linearly correlated with the reduction in rate pressure product (RPP). Serious symptoms of dizziness occurred significantly more frequently on mibefradil (P<0.05), and 19 patients on mibefradil withdrew from trial. CONCLUSIONS: Calcium channel blockers with negative chronotropic properties provide greater delay of ischaemia in patients with exercise-induced angina, but the concomitant risk of intolerable dizziness attenuates this benefit.  (+info)