Traumatic stress exposure increases noradrenaline (NA) release, which contributes to anxiety and impaired risk-appraisal. Guanfacine, a selective alpha-2A adrenergic receptor agonist, has been used to treat stress-related disorders characterised by impaired prefrontal cortex function. By acting on both presynaptic inhibitory autoreceptors and postsynaptic heteroreceptors, guanfacine attenuates stress reactivity and enhances cognition.
View Article and Find Full Text PDFBackground: Complaints of ethical and professional misconduct are lodged and processed by the Health Professions Council of South Africa (HPCSA) in accordance with their legal mandate.
Objectives: This study describes the nature and frequency of transgressions by physiotherapists as concluded by the HPCSA for the period from 2010 to 2020.
Method: A total sampling method was used to extract all records of transgressions lodged against physiotherapists between 2010 and 2020.
The global practice of monetizing ecosystems to further national economic development has laid fertile ground for the COVID-19 pandemic and others like it, writes Cobus van Staden.
View Article and Find Full Text PDFCognitive flexibility, shown to be impaired in patients presenting with compulsions, is dependent on balanced dopaminergic and serotonergic interaction. Towards the development of a zebrafish (Danio rerio) screening test for anti-compulsive drug action, we manipulated social reward appraisal under different contexts by means of dopaminergic (apomorphine) and serotonergic (escitalopram) intervention. Seven groups of zebrafish (n = 6 per group) were exposed for 24 days (1 h per day) to either control (normal tank water), apomorphine (50 or 100 μg/L), escitalopram (500 or 1000 μg/L) or a combination (A100/E500 or A100/E1000 μg/L).
View Article and Find Full Text PDFBackground: Society invests huge financial resources in training medical students. However, the academic and personal demands placed on these students can be taxing and may be detrimental to students' quality of life leading to high levels of burnout and academic dropout rates.
Aim: To determine the association between the levels of burnout and quality of life among fourth-year medical students at the University of the Free State (UFS).
Background: One of the ethical imperatives for a valid consent process in clinical medication trials is that the process be guided by and recorded in an informed consent document (ICD). Concerns have been expressed, however, about readability and participant understanding of ICDs, which are often 10-20 pages long. Objective measures of readability and understanding have been used to support these concerns in several articles, but surprisingly the voice of trial participants on ICDs has not been heard in previous studies.
View Article and Find Full Text PDFPsychiatric expert testimony is challenging in cases of violence when the accused person submits a defence that he or she was so overwhelmed by emotions triggered by an upsetting event that his or her violent behaviour was an uncontrollable consequence of the emotions. This defence is usually presented in terms of an automatism particularly not attributed to a mental disorder. Clouding testimony in these cases is the various definitions of both automatism and mental disorder-definitions by which the jurisprudential distinction is made between a sane and an insane automatism, or pathological and non-pathological incapacity (NPCI).
View Article and Find Full Text PDFGlobal inequalities contribute to marked disparities in health and wellness of human populations. Many opportunities now exist to provide health care to all people in a person- and people-centered way that is effective, equitable, and sustainable. We review these opportunities and the scientific, historical, and philosophical considerations that form the basis for the International College of Person-centered Medicine's 2014 Using consistent time-series data, we critically examine examples of universal healthcare systems in Chile, Spain, and Cuba.
View Article and Find Full Text PDFThe bile salt export pump (BSEP) is expressed at the canalicular domain of hepatocytes, where it serves as the primary route of elimination for monovalent bile acids (BAs) into the bile canaliculi. The most compelling evidence linking dysfunction in BA transport with liver injury in humans is found with carriers of mutations that render BSEP nonfunctional. Based on mounting evidence, there appears to be a strong association between drug-induced BSEP interference and liver injury in humans; however, causality has not been established.
View Article and Find Full Text PDFCurr Protoc Toxicol
November 2012
The use of plasma membrane vesicles that overexpress the bile salt export pump (BSEP) or multidrug resistance-associated protein 2, 3, or 4 (MRP2-4) with an in vitro vacuum filtration system offers a rapid and reliable means for screening drug candidates for their effects on transporter function in hepatocytes and thus their potential for causing drug-induced liver injury (DILI). Comparison of transporter activity in the presence and absence of ATP allows for determination of a specific assay window for each transporter. This window is used to determine the degree to which each test compound inhibits transporter activity.
View Article and Find Full Text PDFThe bile salt export pump (BSEP) is an efflux transporter, driving the elimination of endobiotic and xenobiotic substrates from hepatocytes into the bile. More specifically, it is responsible for the elimination of monovalent, conjugated bile salts, with little or no assistance from other apical transporters. Disruption of BSEP activity through genetic disorders is known to manifest in clinical liver injury such as progressive familial intrahepatic cholestasis type 2.
View Article and Find Full Text PDFAssay Drug Dev Technol
June 2009
The ability to combine primary hit identification assays with target profiling would significantly streamline the current drug discovery process. Working towards this end, we report here the development of a microarray-based ligand binding assay that supports multiplexed analysis of G protein-coupled receptor systems in a 96-well microplate format that is compatible with the equipment and infrastructure typical of high-throughput screening laboratories. A prototype microarray was generated by pin-printing seven different receptors within the wells of a specially coated glass-bottom microplate and assaying with a cocktail of fluorescent ligands.
View Article and Find Full Text PDFComb Chem High Throughput Screen
September 2009
Drug discovery efforts advance in step with advancements in assay technologies, as new technologies provide new lenses through which biology can be viewed. The novel information gathered results in the better understanding of drug-target interactions leading to better decision making during the drug discovery process. One area of rapid development is within label-free technologies.
View Article and Find Full Text PDFThe G protein-coupled receptor (GPCR) G2A (for G2 accumulation) was identified as a stress-inducible antiproliferative cell cycle regulator. Targeted G2A gene deletion in mice resulted in systemic lupus erythematosus-like and atherosclerotic lesion phenotypes. These findings suggested that G2A may be a therapeutic target for cancers and autoimmune and cardiovascular diseases.
View Article and Find Full Text PDFBackground: Fast-growing Eucalyptus grandis trees are one of the most efficient producers of wood in South Africa. The most serious problem affecting the quality and yield of solid wood products is the occurrence of end splitting in logs. Selection of E.
View Article and Find Full Text PDFThe measurement of ligand receptor binding parameters for G-protein-coupled receptors is indispensable in the drug discovery process. Traditional ligand receptor binding assays require scale-up of cells and membrane preparations, which is an expensive and time-consuming process. In this report, the authors describe the development of a homogeneous live-cell binding assay for GPCRs using a fluorophore-labeled nonpeptide ligand.
View Article and Find Full Text PDFThe Epic cell assay technology (Corning Inc., Corning, NY) uses a resonant waveguide grating optical biosensor to measure cellular response to ligands manifested through dynamic mass redistribution (DMR) of cellular contents. The DMR measurement is a noninvasive, label-free assay that can be used to assess the pharmacological properties of compounds.
View Article and Find Full Text PDFWe report the discovery of chroman 28, a potent and selective antagonist of human, nonhuman primate, rat, and rabbit bradykinin B1 receptors (0.4-17 nM). At 90 mg/kg s.
View Article and Find Full Text PDFPsychol Psychother
September 2006
From 73 patients, 10 with the best, and 10 with the worst outcomes after psychotherapy were compared statistically for the frequency of 'not' and 'never' at commencement of psychotherapy, and for change in their frequency after therapy. A highly statistically significantly difference was found at commencement of psychotherapy in that the negative was used more frequently by the worst outcome group (p=.006).
View Article and Find Full Text PDFMelanin-concentrating hormone (MCH) is a cyclic 19 amino acid orexigenic neuropeptide. The action of MCH on feeding is thought to involve the activation of its respective G protein-coupled receptor MCH-R1. Consequently, antagonists that block MCH regulated MCH-R1 activity may provide a viable approach to the treatment of diet-induced obesity.
View Article and Find Full Text PDFObjective: To examine changes in linguistic markers in the course of psychotherapy, drawing on Frege's logic of relations to define semantic variables distinct from syntactic variables.
Method: From a sample of 73 patients, 10 patients with the best and 10 patients with the worst outcomes were selected. Forty transcribed sessions of each outcome group were compared statistically for change between commencement and termination of psychotherapy in: (i) the syntactic usage of first person pronouns ('I', 'me', 'we', 'us', 'implied I', 'implied me'); (ii) semantic usage of first person pronouns (expressing alpha, omega, or unclear positions); and (iii) non-pronoun linguistic variables (passive voice, negative, copula, auxiliary verbs expressing a sense of obligation).
What renders some mentally disordered patients incapable of informed consent to medical interventions? It is argued that a patient is incapable of giving informed consent owing to mental disorder, if a mental disorder prevents a patient from understanding what s/he consents to; if a mental disorder prevents a patient from choosing decisively; if a mental disorder prevents a patient from communicating his/her consent; or if a mental disorder prevents a patient from accepting the need for a medical intervention. This paper holds that a patient's capacity to give informed consent should be assessed clinically by using these conditions necessary for informed consent, and should be assessed specifically for each intervention and specifically at the time when the consent has to be given. The paper considers patients' incapacity to give informed consent to treatment, to give informed consent to be examined clinically, and to give informed consent to participate in research.
View Article and Find Full Text PDFAm J Vet Res
November 2001
Objective: To determine potency and selectivity of nonsteroidal anti-inflammatory drugs (NSAID) and cyclooxygenase- (COX-) specific inhibitors in whole blood from horses, dogs, and cats.
Sample Population: Blood samples from 30 healthy horses, 48 healthy dogs, and 9 healthy cats.
Procedure: Activities of COX-1 and COX-2 were determined by measuring coagulation-induced thromboxane and lipopolysaccharide-induced prostaglandin E2 concentrations, respectively, in whole blood with and without the addition of various concentrations of phenylbutazone, flunixin meglumine, ketoprofen, diclofenac, indomethacin, meloxicam, carprofen, 5-bromo-2[4-fluorophenyl]-3-14-methylsulfonylphenyl]-thiophene (DuP 697), 5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl) phenyl-2(5H)-furan one (DFU), 3-(3,4-difluorophenyl)-4-(4-(methylsulfonyl)phenyl)-2-(5H)-furanone (MF-tricyclic), and celecoxib.