155 research outputs found
The Influence of the CYP2C19 and CYP2D6 genetic polymorphisms on oxidative drug metabolism / Janet K. Coller.
No full textAmendements: leaves 252-254.Copies of author's previously published articles inserted.Bibliography: leaves 226-251.vi, 254 leaves : ill. ; 30 cm.The CYP2C19 and CYP2D6 genetic polymorphisms control the oxidative metabolism of many different drug classes. Populations are separated into groups of extensive metabolisers (EM), poor metabolisers (PM), and in the case of CYP2D6, ultra-rapid metabolisers (UM). In vitro studies using human liver microsomes were conducted to examine the kinetics of the oxidative metabolism of flunitrazepam, and which CYP450 enzymes mediate the oxidative metabolism of flunitrazepam, (S)-mephenytoin and proguanil.Thesis (Ph.D.)--University of Adelaide, Dept. of Clinical and Experimental Pharmacology, 200
Validation of an LC-MS/MS method for the quantification of mycophenolic acid in human kidney transplant biopsies
No full textAbstract not availableZaipul I. Md Dom, Benjamin D. Noll, Janet K. Coller, Andrew A. Somogyi, Graeme R. Russ, Dennis A. Hesselink, Teun van Gelder, Benedetta C. Sallusti
Irinotecan-induced gastrointestinal dysfunction and pain are mediated by common TLR4-dependent mechanisms
No full textPublished Online First March 29, 2016Abstract not availableHannah R. Wardill, Rachel J. Gibson, Ysabella Z.A. Van Sebille, Kate R. Secombe, Janet K. Coller, Imogen A. White, Jim Manavis, Mark R. Hutchinson, Vasiliki Staikopoulos, Richard M. Logan, and Joanne M. Bowe
Alcohol-induced sedation and synergistic interactions between alcohol and morphine: a key mechanistic role for Toll-like receptors and MyD88-dependent signaling
No full textAbstract not availableFrances Corrigan, Yue Wu, Jonathan Tuke, Janet K. Coller, Kenner C. Rice, Kerrilyn R. Diener, John D. Hayball, Linda R. Watkins, Andrew A. Somogyi, Mark R. Hutchinso
T.T. Cloete as literary critic, theorist and literary historian (Part 2): T.T. Cloete as theorist of literary history
No full textIt had already been stated that Siegfried Schmidt (in Hjort 1992) discerned four ‘roles’ within the Literary System, that of literary production, dissemination, reception and literary processing. According to this definition, T.T. Cloete, the well-known author and critic, had played all of these roles. In this second part of a two-part article the focus is on Cloete as a literary historian and in particular on his theoretical (methodological) perceptions pertaining to literary history. It is abundantly clear that in all of his different roles a historical awareness was always present. For Cloete the literary work of art was inbedded in a historical timeframe which imposed hermeneutical imperatives on the critic; on the other hand the literary work of art is present in the here and now and accessible to any skilled reader. One of the objectives of this study is to argue that there was thus an implied dichotomy in Cloete’s thinking on literary history. On the one hand there had been a relativistic view that positioned literary texts in the past, and on the other hand a normative view that implied that certain texts (due to inherent qualities like integration and complexity) could gain a certain permanence. In the last part of this article-true to the narrative approach, an implied confrontation with Cloete’s (methodological) views of literary history lead to a personal standpoint as a confrontation with the self (cf. Sools 2009:27). This explication of a personal view on the writing of a literary history (as an implied homage to Cloete) concluded the article
TLR4-dependent claudin-1 internalization and secretagogue-mediated chloride secretion regulate irinotecan-induced diarrhea
No full textPublished OnlineFirst August 22, 2016Abstract not availableHannah R.Wardill, Joanne M. Bowen, Ysabella Z.A. Van Sebille, Kate R. Secombe, Janet K. Coller, Imogen A. Ball, Richard M. Logan, and Rachel J Gibso
Association between the DRD2 A(1) allele and response to methadone and buprenorphine maintenance treatments
No full textThe definitive version is available at www3.interscience.wiley.com.The TaqI A polymorphism (A(1)) of the dopamine D(2) receptor gene (DRD2), although not a specific predictor of opioid dependence, has been strongly associated with high levels of prior heroin use and poor treatment outcomes among methadone maintenance patients. The aims of this study were to confirm these findings via a retrospective analysis of A(1) allele frequency in methadone (n = 46) and buprenorphine (n = 25) patients, and non-opioid-dependent controls (n = 95). Subjects were genotyped at the DRD2 TaqI A locus using PCR amplification followed by TaqI restriction enzyme digestion and gel electrophoresis. For methadone and buprenorphine subjects, heroin use (prior to treatment), treatment outcomes, and withdrawal occurrence were determined from comprehensive case notes. No significant differences in A(1) allele frequency (%) were observed between: methadone (19.6%), buprenorphine (18.0%), and control (17.9%) groups (P > 0.7); successful and poor treatment outcome groups, methadone: 20.0% and 19.2%, respectively (P = 1.0); buprenorphine: 18.4% and 20.0%, respectively (P = 1.0). Also, there were no significant relationships between TaqI A genotype and prior heroin use (P = 0.47). However, among the successful methadone subjects, significantly fewer A(1) allele carriers experienced withdrawal than non-A(1) carriers (P = 0.04). In conclusion, the DRD2 genotype effects did not affect opioid maintenance treatment outcomes. This suggests the need for a further prospective investigation into the role of the DRD2 A(1) allele in heroin use and response to maintenance pharmacotherapies for opioid dependence.Daniel T. Barratt, Janet K. Coller and Andrew A. Somogy
Implications of central immune signaling caused by drugs of abuse: Mechanisms, mediators and new therapeutic approaches for prediction and treatment of drug dependence
No full textIn the past two decades a trickle of manuscripts examining the non-neuronal central nervous system immune consequences of the drugs of abuse has now swollen to a significant body of work. Initially, these studies reported associative evidence of central nervous system proinflammation resulting from exposure to the drugs of abuse demonstrating key implications for neurotoxicity and disease progression associated with, for example, HIV infection. However, more recently this drug-induced activation of central immune signaling is now understood to contribute substantially to the pharmacodynamic actions of the drugs of abuse, by enhancing the engagement of classical mesolimbic dopamine reward pathways and withdrawal centers. This review will highlight the key in vivo animal, human, biological and molecular evidence of these central immune signaling actions of opioids, alcohol, cocaine, methamphetamine, and 3,4-methylenedioxymethamphetamine (MDMA). Excitingly, this new appreciation of central immune signaling activity of drugs of abuse provides novel therapeutic interventions and opportunities to identify 'at risk' individuals through the use of immunogenetics. Discussion will also cover the evidence of modulation of this signaling by existing clinical and pre-clinical drug candidates, and novel pharmacological targets. Finally, following examination of the breadth of central immune signaling actions of the drugs of abuse highlighted here, the current known common immune signaling components will be outlined and their impact on established addiction neurocircuitry discussed, thereby synthesizing a common neuroimmune hypothesis of addiction.Janet K. Coller, Mark R. Hutchinso
Diarrhea Induced by Small Molecule Tyrosine Kinase Inhibitors Compared With Chemotherapy: Potential Role of the Microbiome.
No full textSmall molecule receptor tyrosine kinase inhibitors (SM-TKIs) are among a group of targeted cancer therapies, intended to be more specific to cancer cells compared with treatments, such as chemotherapy, hence reducing adverse events. Unfortunately, many patients report high levels of diarrhea, the pathogenesis of which remains under investigation. In this article, we compare the current state of knowledge of the pathogenesis of chemotherapy-induced diarrhea (CID) in comparison to SM-TKI–induced diarrhea, and investigate how a similar research approach in both areas may be beneficial. To this end, we review evidence that both treatment modalities may interact with the gut microbiome, and as such the microbiome should be investigated for its ability to reduce the risk of diarrhea.Kate R. Secombe, Ysabella Z. A. Van Sebille, Bronwen J. Mayo, Janet K. Coller, Rachel J. Gibson, and Joanne M. Bowe
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