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Basic & Clinical Pharmacology & Toxicology

Daniel Pilsgaard Henriksen, Per Damkier, Jesper Hallas, Mads Nybo
Register-based administrative data comprise the backbone of pharmacoepidemiological research.. However, information from these registers lack biochemical details.. The aim of our study was to describe the creation, coverage and content of the Funen Laboratory Cohort (FLaC). The Funen Laboratory Cohort (FLaC) is a database comprising all inhabitants of Funen, Denmark, who in the study period of January 2000 to December 2015 had their creatinine levels measured. Data were linked to the Danish nationwide registers with information on vital status, redeemed prescriptions, discharge diagnoses and socioeconomic status...
November 12, 2018: Basic & Clinical Pharmacology & Toxicology
Michelle Khai Khun Yap, Nurhamimah Misuan
Type II diabetes mellitus (T2DM) is a chronic non-communicable disease due to abnormal insulin actions causing uncontrolled hyperglycaemia. The treatment for T2DM, for instance, metformin and incretin mimetic, mainly focuses on the restoration of insulin sensitivity and secretion. Exendin-4 is a short incretin-mimetic peptide consisting of 39 amino acids. It is discovered in the venom of Heloderma suspectum as a full agonist for the glucagon-like peptide 1 (GLP-1) receptor and produces insulinotropic effects...
November 12, 2018: Basic & Clinical Pharmacology & Toxicology
Troels K Bergmann, Mette Marie H Christensen, Daniel Henriksen, Maija Bruun Haastrup, Per Damkier
Overall survival (OS) is the undisputed gold standard efficacy endpoint in cancer drug trials. It is with growing concern that we observe how progression-free survival (PFS) gains ground as surrogate endpoint in its place. PFS has appeal because it is resource-efficient, but it has severe shortcomings. Our concern is that uncritical use of PFS will harm the evidence-based evaluation of cancer drugs when considering them for standard use in publicly financed health care systems. PFS is only valid as a surrogate endpoint for OS if it correlates strongly with OS and if the cancer drug being investigated has the same effect on PFS and OS such that effects on one predicts effects on the other...
November 12, 2018: Basic & Clinical Pharmacology & Toxicology
Yun Mi Yu, Seungyeon Kim, Kyung Hee Choi, Kyeong Hye Jeong, Euni Lee
This study aimed to determine the level of pharmacovigilance (PV) education in pharmacy programs and to evaluate the predictive factors for the intent to report adverse drug reactions (ADRs) by pharmacy students in South Korea. Self-administered questionnaires were collected from a regionally stratified nationwide convenience sample of pharmacy students in September 2017. The association between students' intent to report ADRs and their knowledge and attitude was evaluated by using multivariate logistic regression analysis...
November 11, 2018: Basic & Clinical Pharmacology & Toxicology
Antti Pemmari, Erja-Leena Paukkeri, Mari Hämäläinen, Tiina Leppänen, Riku Korhonen, Eeva Moilanen
Macrophage polarization refers to the ability of these cells to adopt different functional phenotypes according to their environment. Mitogen-activated protein kinase phosphatase-1 (MKP-1) is known to regulate the classical lipopolysaccharide (LPS) -induced pro-inflammatory macrophage activation and the inflammatory response. Here, we investigated the effects of MKP-1 on the anti-inflammatory and healing-promoting macrophage phenotype induced by cytokines IL-4 and IL-13 and examined the potential mediator role of MKP-1 in glucocorticoid effects on the two macrophage phenotypes...
November 2, 2018: Basic & Clinical Pharmacology & Toxicology
Purificación Cid-Silva, Noelia Fernández-Bargiela, Luis Margusino-Framiñán, Vanesa Balboa-Barreiro, Álvaro Mena-De-Cea, Soledad López-Calvo, Pilar Vázquez-Rodríguez, Isabel Martín-Herranz, Enrique Míguez-Rey, Eva Poveda-López, Ángeles Castro-Iglesias
Two elvitegravir/cobicistat-based therapies combined with emtricitabine/tenofovir disoproxil fumarate (EVG/c/FTC/TDF) or emtricitabine/tenofovir alafenamide fumarate (EVG/c/FTC/TAF) are currently available for HIV patients. This study evaluated the modifications in the lipid profile of patients who received these treatments in the last three years at our institution. A retrospective observational study in HIV-infected patients who received EVG/c/FTC/TDF or EVG/c/FTC/TAF from January 2015 to January 2018 at a reference hospital in northwestern Spain was carried out...
November 2, 2018: Basic & Clinical Pharmacology & Toxicology
Philippe Grandjean, Latifa Abdennebi-Najar, Robert Barouki, Carl F Cranor, Ruth A Etzel, David Gee, Jerrold J Heindel, Karin S Hougaard, Patricia Hunt, Tim S Nawrot, Gail S Prins, Beate Ritz, Morando Soffritti, Jordi Sunyer, Pal Weihe
Much progress has happened in understanding developmental vulnerability to preventable environmental hazards. Along with the improved insight, the perspective has widened, and developmental toxicity now involves latent effects that can result in delayed adverse effects in adults or at old age and additional effects transgenerationally transferred to future generations. Although epidemiology and toxicology to an increasing degree are exploring the adverse effects from developmental exposures in humans, the improved documentation has resulted in little progress in protection, and few environmental chemicals are currently regulated to protect against developmental toxicity, whether it be neurotoxicity, endocrine disruption or other adverse outcomes...
November 2, 2018: Basic & Clinical Pharmacology & Toxicology
E Iversen, A C Bodilsen, H Klausen, C Treldal, O Andersen, M Houlind, J Petersen
BACKGROUND: Medication errors due to inaccurate measures of kidney function are common among elderly patients. We investigated differences between estimated glomerular filtration rate (eGFR) based on creatinine and cystatin C and how these differences would affect prescribing recommendations among acutely hospitalized elderly patients. We also identified factors associated with discrepancies between estimates. METHODS: eGFR and chronic kidney disease (CKD) classification were determined for 338 acutely hospitalized elderly patients using equations from Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Berlin Initiative Study (BIS) and Cockcroft-Gault (CG)...
October 29, 2018: Basic & Clinical Pharmacology & Toxicology
J M Moon, B J Chun, Y S Cho
Growing evidence indicates that inflammation is associated with neurological sequelae after CO poisoning. Several scores incorporating the peripheral complete blood cell (CBC) count have been introduced as indicators of systemic inflammation. This study investigated whether these scores can improve the predictive accuracy for long-term neurological outcomes of acute carbon monoxide (CO) poisoning. Two hundred seventy-nine patients who suffered from acute CO poisoning were included. Data on the demographic details, serial peripheral CBC counts and scores based on peripheral CBC counts (neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), platelet-lymphocyte ratio (PLR), systemic immune inflammation index (SII)) over the first 12 hr after presentation together with the clinical course during hospitalization and long-term neurological outcomes were collected...
October 29, 2018: Basic & Clinical Pharmacology & Toxicology
Niu Wan-Jie, Sun Tao, Liu Li, Liu Xiao-Qian, Zhang Ren-Fang, Yin Lin, Wang Jiang-Rong, Jia Xiao-Fang, Lu Hong-Zhou, Zhong Ming-Kang, Jiao Zheng, Zhang Li-Jun
Lopinavir (LPV) is a protease inhibitor (PI) for the treatment of human immunodeficiency virus (HIV) infections. Current studies on LPV are mainly focused on Caucasians, and none have investigated the population pharmacokinetics (PPK) of LPV in Chinese population. The present study aimed to develop a PPK model for oral LPV in Chinese adults who are HIV-infected. A total of 460 LPV concentrations from 174 Chinese patients who received LPV/ritonavir (LPV/r) 400/100 mg orally every 12 hr (q12h) were analysed using the non-linear mixed-effects modelling approach...
October 22, 2018: Basic & Clinical Pharmacology & Toxicology
Miriam Saiz-Rodríguez, Dolores Ochoa, Carmen Belmonte, Manuel Román, Cristina Martínez-Ingelmo, Lucía Ortega-Ruíz, Carmen Sarmiento-Iglesias, Coral Herrador, Francisco Abad-Santos
Mercaptopurine is a drug commonly used in the treatment of different types of cancer, especially acute lymphoblastic leukaemia, and autoimmune diseases such as ulcerative colitis or Crohn's disease and in patients receiving organ transplants. It is metabolized by three cytosolic enzymes. One of them, thiopurine-S-methyltransferase (TPMT), is responsible for catalysing the methylation reaction of mercaptopurine to 6-methyl-mercaptopurine, thus inactivating the drug. Individuals with TPMT loss-of-function alleles (*2, *3A, *3B or *3C) can be extremely sensitive to the effect of mercaptopurine, since it can be accumulated, therefore producing haematological toxicity...
October 22, 2018: Basic & Clinical Pharmacology & Toxicology
Kim Brøsen
No abstract text is available yet for this article.
October 19, 2018: Basic & Clinical Pharmacology & Toxicology
Katharina Schmidt-Mende, Björn Wettermark, Morten Andersen, Monique Elsevier, Juan-Jesus Carrero, Tero Shemeikka, Jan Hasselström
The aim of this population-based, cross-sectional study was to analyse the prevalence of renally inappropriate medicines (RIMs) in older people with renal impairment. We included 30 372 people aged ≥65 years with chronic kidney disease (CKD) stage 3, and 2161 with stage 4 attending primary care in Stockholm, Sweden. We used data derived from SCREAM, a database linking patient-specific data on demography, morbidity, healthcare consumption and dispensed drugs to creatinine measurements. Estimated glomerular filtration rate was calculated with CKD-EPI based on the first non-hospital serum creatinine in 2010...
October 17, 2018: Basic & Clinical Pharmacology & Toxicology
Dong-Ho Bak, Mi Ji Choi, Esther Lee, Tae-Rin Kwon, Jong Hwan Kim, Sang-Hyun Nam, Kyoung-Yun Kim, Seung Won Ahn, Seog-Kyun Mun, Jungtae Na, Beom Joon Kim
Botulinum toxin A (BoNT-A) is used clinically for various muscle disorders and acts by preventing the release of the neurotransmitter acetylcholine into the synapse space. Here, we compared the efficacy of prabotulinumtoxinA (PRA) and onabotulinumtoxinA (ONA) for the reduction in hypertrophy in myostatin-deficient (Mstn-/- ) mice. Two different BoNT-A products (2.5, 10 and 25 U/kg) were injected to paralyse the hindlimb for 2 months, after which sciatic nerve conduction study, 3D micro-CT, haematoxylin and eosin (H&E) and dystrophin staining were conducted...
October 16, 2018: Basic & Clinical Pharmacology & Toxicology
Per Damkier, Dorte Lassen, Mette Marie Hougaard Christensen, Kenneth Grønkjaer Madsen, Maja Hellfritzsch, Anton Pottegård
Delta-9-tetrahydrocannabinol (THC), the main psychoactive cannabinoid in cannabis, may inhibit the cytochrome P450 enzyme CYP2C9. Consequently, cannabis use might infer a risk of drug-drug interaction with substrates for this enzyme, which includes drugs known to have a narrow therapeutic window. In this study, we describe a case report of a 27-year-old man treated with warfarin due to mechanical heart valve replacement who presented with elevated international normalized ratio (INR) value (INR = 4.6) following recreational cannabis use...
October 16, 2018: Basic & Clinical Pharmacology & Toxicology
Oak-Sung Choo, Dukyong Yoon, Young Choi, Soojung Jo, Ho-Min Jung, Jun Young An, Yun-Hoon Choung
Hearing loss in the elderly causes communication difficulties, decreased quality of life, isolation, loneliness and frustration. The aim of this study was to identify the modifiable variables that may affect the progression of hearing loss in the elderly. A case-control study was conducted using two datasets. Data were extracted from the health examination survey of Ajou University Hospital (2010-2014) and the Korea National Health and Nutrition Examination Survey (2009-2012) datasets. Audiometry data were evaluated according to variables such as age, sex and drug use for underlying diseases...
October 16, 2018: Basic & Clinical Pharmacology & Toxicology
Maria E Lopes Pires, Ana C Antunes Naime, Jessica G F Oliveira, Gabriel F Anhe, Oliver Garraud, Fabrice Cognasse, Edson Antunes, Sisi Marcondes
Thrombocytopenia during sepsis is associated with a less favourable clinical outcome. Overproduction of reactive-oxygen species (ROS) by different cell types contributes to sepsis. Platelets generate ROS, but the upstream pathways of NADPH oxidase activation are not completely understood. Here, we designed experiments in washed platelets from lipopolysaccharide (LPS)-treated rats to investigate the p47phox activation and ROS generation, and its modulation by c-Src-family kinase (c-Src), phosphoinositide 3-kinase (PI3K), protein kinase C (PKC) and protein kinase G (PKG)...
October 14, 2018: Basic & Clinical Pharmacology & Toxicology
Jessica Sabbatine Chimini, Jose Sergio Possomato-Vieira, Maria Luiza Santos da Silva, Carlos A Dias-Junior
preeclampsia and hypertensive disorders of pregnancy are frequently associated with feto-placental growth restriction and that may be triggered by angiogenic imbalance and endothelial dysfunction. Impaired nitric oxide (NO) bioavailability seems to be involved in these pathophysiological changes observed in hypertensive pregnancy. Pravastatin has shown efficacy and to be safe during hypertension in pregnancy. However, NO involvement in pravastatin effects during maternal hypertension and feto-placental development is unclear...
October 14, 2018: Basic & Clinical Pharmacology & Toxicology
Louise C Druedahl, Johanne Mølby Hansen, Ellen Linnea Freese, Anna Birna Almarsdóttir, Janine M Traulsen
Medication use is a complex process involving different types of healthcare personnel. This study investigated and compared mandatory medication content in the curricula of six types of healthcare personnel with patient contact. Using content analysis, three independent raters analysed the mandatory medication content for physicians, pharmacists, pharmaconomists, nurses, healthcare assistants, and support workers in the Capital Region of Denmark. Three dimensions were analysed: communication with patients about medication, medication use or pharmacology, and medication formulation and production...
October 12, 2018: Basic & Clinical Pharmacology & Toxicology
Yinglu Guan, Xiang Li, Michihisa Umetani, Krishna M Boini, Pin-Lan Li, Yang Zhang
Amitriptyline is a tricyclic antidepressant and an inhibitor of lysosomal acid sphingomyelinase (ASM). Amitriptyline is well-known for its cardiovascular side effects and toxicity in psychiatric patients. However, the mechanisms underlying the cardiovascular side effects of amitriptyline remain largely undefined. This study aimed to determine the effects of amitriptyline on angiogenic capability of vascular endothelial cells in physiological settings and identify its mechanism of action. The ex vivo aortic ring angiogenesis and in vitro cultured endothelial cell tube formation assay were used to assess the effects of amitriptyline on endothelial angiogenic capability...
October 12, 2018: Basic & Clinical Pharmacology & Toxicology
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