Variety Of Drugs (variety + of_drug)

Distribution by Scientific Domains


Selected Abstracts


Sulfation of nitrotyrosine: Biochemistry and functional implications

IUBMB LIFE, Issue 10 2007
Ming-Cheh Liu
Abstract Nitration of tyrosine, in both protein-bound form and free amino acid form, can readily occur in cells under oxidative/nitrative stress. In addition to serving as a biomarker of oxidative/nitrative stress, elevated levels of nitrotyrosine have been shown to cause DNA damage or trigger apoptosis. An important issue is whether the human body is equipped with mechanisms to counteract the potentially harmful effects of nitrotyrosine. Sulfate conjugation, as mediated by the cytosolic sulfotransferases (SULTs), is widely used for the biotransformation and disposal of a variety of drugs and other xenobiotics, as well as endogenous thyroid/steroid hormones and catecholamine neurotransmitters. Recent studies have revealed that the sulfation of nitrotyrosine occurs in cells under oxidative/nitrative stress, and have pinpointed the SULT1A3 as the responsible SULT enzyme. In this review, we summarized the available information concerning the biochemistry of nitrotyrosine sulfation and the effects of genetic polymorphisms on the nitrotyrosine sulfating activity of SULT1A3. Functional implications of the sulfation of nitrotyrosine are discussed. IUBMB Life, 622-627, 2007 [source]


Biliary excretion of technetium-99m-sestamibi in wild-type dogs and in dogs with intrinsic (ABCB1-1, mutation) and extrinsic (ketoconazole treated) P-glycoprotein deficiency

JOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2009
J. C. COELHO
P-glycoprotein (P-gp), the product of ABCB1 gene, is thought to play a role in the biliary excretion of a variety of drugs, but specific studies in dogs have not been performed. Because a number of endogenous (ABCB1 polymorphisms) and exogenous (pharmacological P-gp inhibition) factors can interfere with normal P-gp function, a better understanding of P-gp's role in biliary drug excretion is crucial in preventing adverse drug reactions and drug,drug interactions in dogs. The objectives of this study were to compare biliary excretion of technetium-99m-sestamibi (99mTc-MIBI), a radio-labelled P-gp substrate, in wild-type dogs (ABCB1 wild/wild), and dogs with intrinsic and extrinsic deficiencies in P-gp function. Dogs with intrinsic P-gp deficiency included ABCB1 mut/mut dogs, and dogs with presumed intermediate P-gp phenotype (ABCB1 mut/wild). Dogs with extrinsic P-gp deficiency were considered to be ABCB1 wild/wild dogs treated with the P-gp inhibitor ketoconazole (5 mg/kg PO q12h × 9 doses). Results from this study indicate that ABCB1 mut/mut dogs have significantly decreased biliary excretion of 99mTc-MIBI compared with ABCB1 wild/wild dogs. Treatment with ketoconazole significantly decreased biliary excretion of 99mTc-MIBI in ABCB1 wild/wild dogs. P-gp appears to play an important role in the biliary excretion of 99mTc-MIBI in dogs. It is likely that concurrent administration of a P-gp inhibitor such as ketoconazole will decrease P-gp-mediated biliary excretion of other substrate drugs as well. [source]


Nanotechnology advances in controlled drug delivery systems

PHYSICA STATUS SOLIDI (C) - CURRENT TOPICS IN SOLID STATE PHYSICS, Issue 12 2008
C. Kiparissides
Abstract Nanotechnology advances in drug delivery deal with the development of synthetic nanometer sized targeted delivery systems for therapeutic agents of increased complexity, and biologically active drug products. Therapeutic systems in this class are up to a million times larger than classical drugs like aspirin. Being larger there is more scope for diversity and complexity, which makes their protection much more challenging and their delivery more difficult. Their increased complexity however, gives these systems the unique power to tackle more challenging diseases. Targeted delivery systems can have multiple functions, a key one being their ability to recognize specific molecules which can be located either on the membrane of target cells, or in specific compartments within the cell. A challenging objective of targeted drug delivery is the development of innovative multidisciplinary approaches for the design, synthesis and functionalization of novel nanocarriers for targeted delivery of protein/peptide (P/P) drugs via oral, pulmonary and nasal administration routes as well as the fabrication of "smart" miniaturized drug delivery devices able to release a variety of drugs on demand. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source]


Naloxone-responsive acute dystonia and parkinsonism following general anaesthesia

ANAESTHESIA, Issue 12 2009
I. A. Iselin-Chaves
Summary Various movement disorders such as dystonia may acutely develop during or at emergence from general anaesthesia in patients with or without pre-existing Parkinson disease. These movements are triggered by a variety of drugs including propofol, sevoflurane, anti-emetics, antipsychotics and opioids. The postulated mechanism involves an imbalance between dopaminergic and cholinergic neurotransmitters in the basal ganglia. We report an acute, severe and generalised dystonic reaction in an otherwise healthy woman at emergence from general anaesthesia, dramatically reversed by the administration of naloxone, pointing to a potential role of the fentanyl and morphine that the patient had received. Recent literature on the mechanisms of abnormal movements induced by opioids are discussed. The severity of the reaction with usual doses of opioids, in a patient with no prior history of parkinsonism, led to further investigation that demonstrated the possibility of an enhanced susceptibility to opioids, involving a genetically determined abnormal function of glycoproteine-P and catechol-O-methyltransferase. [source]


Microarray analysis of murine limb bud ectoderm and mesoderm after exposure to cadmium or acetazolamide

BIRTH DEFECTS RESEARCH, Issue 7 2009
Claire M. Schreiner
Abstract BACKGROUND: A variety of drugs, environmental chemicals, and physical agents induce a common limb malformation in the offspring of pregnant mice exposed on day 9 of gestation. This malformation, postaxial, right-sided forelimb ectrodactyly, is thought to arise via an alteration of hedgehog signaling. METHODS: We have studied two of these teratogens, acetazolamide and cadmium, using the technique of microarray analysis of limb bud ectoderm and mesoderm to search for changes in gene expression that could indicate a common pathway to postaxial limb reduction. RESULTS: Results indicated a generalized up-regulation of gene expression after exposure to acetazolamide but a generalized down-regulation due to cadmium exposure. An intriguing observation was a cadmium-induced reduction of Mt1 and Mt2 expression in the limb bud mesoderm indicating a lowering of embryonic zinc. CONCLUSIONS: We propose that these two teratogens and others (valproic acid and ethanol) lower sonic hedgehog signaling by perturbation of zinc function in the sonic hedgehog protein. Birth Defects Research (Part A), 2009. © 2009 Wiley-Liss, Inc. [source]