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Basic & Clinical Pharmacology & Toxicology

Sorayya Kheirouri, Mohammad Alizadeh
No abstract text is available yet for this article.
July 19, 2018: Basic & Clinical Pharmacology & Toxicology
Nadia Raci Marques Pereira, Sergio Tufik, Helena Hachul
No abstract text is available yet for this article.
July 19, 2018: Basic & Clinical Pharmacology & Toxicology
J J van Wattum, T M Leferink, B Wilffert, P G J Ter Horst
Breastfeeding is important for the development of the child. Many antibiotics are considered safe during breastfeeding. The aim of the study was to assess the quality of lactation studies with antibiotics using the FDA and International Lacation Consultant Association (ILCA) quality guidelines for lactation studies. The secondary goal was to determine the exposure of the breastfed infant to antibiotics in relation to bacterial resistance and the developing microbiome. A literature search was performed and the included studies were scored on methodology, parameters concerning maternal exposure to antibiotics, maternal plasma and milk sampling...
July 17, 2018: Basic & Clinical Pharmacology & Toxicology
Hyunah Kim, Seo Yeon Baik, So Jung Yang, Tong Min Kim, Seung-Hwan Lee, Jae Hyoung Cho, In Young Choi, Ju Han Kim, Kun-Ho Yoon, Hun-Sung Kim
Although angiotensin-converting enzyme inhibitor-related angioedema is well known, angiotensin II receptor blocker (ARB)-related angioedema has not been extensively studied because of its lower incidence. Therefore, ARB-related angioedema is likely to be overlooked in the clinical setting. We analysed the medical records of adults who had been prescribed ARB and diagnosed with angioedema between 2009 and 2015. All adults over the age of 18 years who were initially administered ARB between 1 January 2009 and 31 December 2015 were selected as participants in this study...
July 13, 2018: Basic & Clinical Pharmacology & Toxicology
Virva Hyttinen, Johanna Jyrkkä, Leena K Saastamoinen, Anna-Kaisa Vartiainen, Hannu Valtonen
Potentially inappropriate medications (PIMs) in older persons are defined as medications of which the potential harms outweigh their benefits. The purpose of this study was determine how initiation of PIMs accumulate in community-dwelling persons aged 65-74 and ≥75 years, and which patient- and health care-related factors are associated with PIM initiation over time. Data of this study were gathered from population-based registers by a 10% random sample of persons (n = 28,497) aged ≥65 years with no prior PIMs within a 2-year period preceding the index date (1 January 2002) and the study subjects were followed until 2013...
July 13, 2018: Basic & Clinical Pharmacology & Toxicology
Ivana Ivanova, Monique Elseviers, Bjorn Wettermark, Katharina Schmidt Mende, Robert Vander Stichele, Thierry Christiaens
AIM: To explore the feasibility of the electronic assessment of potentially inappropriate medication (PIM) criteria in a large administrative database and to explore the validity of the cardiovascular subset of PIM criteria, by studying the association with relevant outcomes. METHOD: A cohort study using administrative data from Stockholm County, Sweden (VAL database). Eligible for inclusion were community-dwelling older people (≥ 65 years), alive in Stockholm County on 31 December 2015...
July 11, 2018: Basic & Clinical Pharmacology & Toxicology
Teemu A Natunen, Mikko Gynther, Hannah Rostalski, Külli Jaako, Aaro J Jalkanen
Prolyl oligopeptidase (PREP) is an abundant peptidase in the brain and periphery, but its physiological functions are still largely unknown. Recent findings point to a role for PREP in inflammatory processes. This study assessed the cellular and extracellular PREP activities in cultures of mouse primary cortical neurons, microglial cells and astrocytes, and immortalized microglial BV-2 cells under neuroinflammatory conditions induced by lipopolysaccharide (LPS) and interferon gamma (IFNγ). Furthermore, we evaluated the neuroprotective effect of a specific PREP inhibitor, KYP-2047, in a neuroinflammation model based on a co-culture of primary cortical neurons and activated BV-2 cells...
July 11, 2018: Basic & Clinical Pharmacology & Toxicology
Thomas Vanhove, Pieter Annaert, Noël Knops, Henriëtte de Loor, Jan de Hoon, Dirk R J Kuypers
The magnitude of interaction between the CYP3A4 substrate tacrolimus and various CYP3A4 inhibitors is highly unpredictable. We investigated whether an individual's baseline in vivo CYP3A4 activity, assessed using the oral midazolam (MDZ) probe, could be used to predict the magnitude of drug-drug interaction between tacrolimus and the potent CYP3A4 inhibitor itraconazole. In a prospective single-arm open-label study, 16 healthy volunteers were administered single doses of MDZ and tacrolimus before and after a 4-day course of itraconazole...
July 10, 2018: Basic & Clinical Pharmacology & Toxicology
Marcus J P Geist, Gerlinde Egerer, Gerd Mikus, Antje Blank, Nicolas Hohmann, Werner J Heinz, Alexandra Carls
Posaconazole prophylaxis is recommended for patients with acute myeloid leukaemia during induction chemotherapy. Although a tablet formulation with better oral bioavailability is available, some patients have to rely on the oral suspension in clinical routine. Therefore, effectiveness of posaconazole oral suspension under real-life clinical conditions and impact of patient education about the correct intake on its plasma concentrations were assessed in this study. Altogether 96 patients receiving 160 cycles of induction chemotherapy were retrospectively (40 patients) and prospectively (56 patients) analysed...
July 10, 2018: Basic & Clinical Pharmacology & Toxicology
Wei Wang, Xiao Wang, Xian-Sheng Zhang, Chao-Zhao Liang
Oxidative stress and inflammatory responses are closely implicated in the progression of renal interstitial fibrosis, thereby leading to chronic kidney disease. Cryptotanshinone(CTS) is a natural compound involved in antioxidant and anti-inflammatory activities. We evaluated the effects of CTS on inflammation and oxidative stress in obstructed kidneys. Mice received gastric gavage of CTS from 7 days before unilateral ureteral obstruction operation to one week after surgery. Administration of CTS at 50 and 100 mg·kg-1 ·day-1 significantly decreased collagen production, as shown by Masson staining...
July 4, 2018: Basic & Clinical Pharmacology & Toxicology
Su-Su Bao, Jian Wen, Qian-Meng Lin, Ying-Hui Li, Yang-Ge Huang, Hong-Yu Zhou, Guo-Xin Hu
The objective of this study was to evaluate the effect of apatinib on the pharmacokinetics of venlafaxine and O-desmethylvenlafaxine in SD rats and the inhibitory effects of apatinib on venlafaxine in rat and human liver microsomes. Twenty-one SD male rats were randomly divided into 3 groups (n=7): group A (multiple dose of 40mg/kg apatinib for 7 days), group B (single dose of 40mg/kg apatinib) and group C (the control group). All samples were measured by UPLC-MS/MS. The results indicated that a single dose of apatinib increased the AUC(0-t) , AUC(0-∞) and Cmax of both venlafaxine and O-desmethylvenlafaxine significantly while Vz/F and CLz/F were decreased...
July 2, 2018: Basic & Clinical Pharmacology & Toxicology
Lili Liang, Zhixin Zhang, Xiaowei Qin, Ying Gao, Peng Zhao, Jing Liu, Weihui Zeng
Malignant melanoma is an aggressive form of cancer which is highly resistant to chemotherapy. We have previously found that gambogic acid (GA), a kind of polyprenylated xanthone, exhibits an anti-tumour role in melanoma. The study was designed to investigate novel mechanisms of the anti-tumour effect of GA in melanoma cells and implanted nude mice. GA significantly decreased cell viability, increased apoptosis and reduced migration and invasion in A375 cells. In addition, cisplatin-induced cytotoxicity in both A375 and A375/CDDP cells was increased by GA...
June 30, 2018: Basic & Clinical Pharmacology & Toxicology
Gianluca Catucci, Stefania Bortolussi, Giulia Rampolla, Debora Cusumano, Gianfranco Gilardi, Sheila J Sadeghi
Human flavin-containing monooxygenase 3 (hFMO3) is a drug-metabolising enzyme that oxygenates many drugs and xenobiotics in the liver. This enzyme is also known to exhibit single nucleotide polymorphisms (SNPs) that can alter the rates of monooxygenation of therapeutic agents. The purpose of this study was to investigate the effect of the three common polymorphic variants of hFMO3 (V257M, E158K and E308G) on the metabolism and clearance of 3 structurally similar compounds: tamoxifen (breast cancer medication), clomiphene (infertility medication) and GSK5182 (anti-diabetic lead molecule)...
June 30, 2018: Basic & Clinical Pharmacology & Toxicology
Kasper F Høyer, Thomas S Nielsen, Steve Risis, Jonas T Treebak, Niels Jessen
The use of anaesthetics severely influences substrate metabolism. This poses challenges for patients in clinical settings and for the use of animals in diabetes research. Sevoflurane can affect regulation of glucose homeostasis at several steps, but the tissue-specific response remains to be determined. The aim of the study was to investigate the pharmacological effect of sevoflurane anaesthesia on glucose homeostasis during hyperinsulinaemic clamp conditions, the gold standard method for assessment of whole-body insulin sensitivity...
June 28, 2018: Basic & Clinical Pharmacology & Toxicology
Anne M Filppula, Tiffany M Mustonen, Janne T Backman
Several protein kinase inhibitors have been reported to affect cytochrome P450 (CYP) 3A by time-dependent inhibition. Herein, we tested a set of six kinase inhibitors for time-dependent inhibition of CYP2C8 and CYP3A4 in human liver microsomes. Dovitinib, midostaurin and nintedanib exhibited an increased inhibition of CYP3A4 after a 30-min. pre-incubation with NADPH, as compared to no pre-incubation (IC50 shift >1.5). Masitinib, trametinib and vatalanib did not affect CYP2C8 or CYP3A4 by time-dependent inhibition (IC50 shift <1...
June 28, 2018: Basic & Clinical Pharmacology & Toxicology
Ricardo Usategui-Martín, Gemma Vega, Laura Abad-Manteca, Marta Ruiz-Mambrilla, Ismael Calero-Paniagua, Antonio Dueñas-Laita, José L Pérez-Castrillón
One of the pleiotropic effects of statins is their capacity to increase bone formation. This is due to, among other things, they modify BMP-2 pathway. Several experimental studies have confirmed that statins have bone anabolic properties but the consequences in bone metabolism in the clinical practice are very variable. Our hypothesis is that the clinical variability in bone metabolism response could be attributed, among other causes, to genetic factors. Therefore, we analysed polymorphisms in BMP-2 gene (rs235768, rs1980499, rs2273073 and rs1005464) in order to evaluate the role of these variants in modulating bone metabolism response to statins treatment in patients with acute coronary syndrome...
June 28, 2018: Basic & Clinical Pharmacology & Toxicology
David H Ipsen, Bidda Rolin, Günaj Rakipovsk, Gry F Skovsted, Anette Madsen, Stefanie Kolstrup, Anne Marie Schou-Pedersen, Josephine Skat-Rørdam, Jens Lykkesfeldt, Pernille Tveden-Nyborg
Although commonly associated with obesity, non-alcoholic fatty liver disease (NAFLD) is also present in the lean population representing a unique disease phenotype. Affecting 25% of the world's population, NAFLD is associated with increased mortality especially when progressed to non-alcoholic steatohepatitis (NASH). However, no approved pharmacological treatments exist. Current research focuses mainly on NASH associated with obesity, leaving the effectiveness of promising treatments in lean NASH virtually unknown...
June 28, 2018: Basic & Clinical Pharmacology & Toxicology
Hong Shen, Danyang Wu, Shanshan Wang, Mengjie Zhao, Wenbo Sun, Xiaozhou Zhu, Ning Zhang, Hui Yao, Qing Cui, Hong Xiao
The prevalence of cardiovascular disease (CVD) is higher in patients with schizophrenia than in the general population. We aimed to investigate whether atypical antipsychotics (AAP) increase the levels of lipoprotein-associated phospholipase A2 (Lp-PLA2), thereby increasing the risk of CVD. The data were from inpatients aged 18 to 60 years with a diagnosis of schizophrenia according to ICD-10 at The Affiliated Brain Hospital of Nanjing Medical University who underwent physical examination between 1 October 2014 and 30 September 2016...
June 25, 2018: Basic & Clinical Pharmacology & Toxicology
Anne E Olesen, Thomas D Nissen, Matias Nilsson, Dina Lelic, Christina Brock, Lona L Christrup, Asbjørn M Drewes
Offset analgesia (OA) is a pain-modulating mechanism described as a disproportionately large decrease in pain intensity evoked by a discrete decrease in stimulus temperature. The role of the opioidergic, serotonergic and noradrenergic systems on OA remains unclear. The aim of the present study was to evaluate whether OA is modulated by an opioid (oxycodone) and a serotonin and noradrenaline reuptake inhibitor (venlafaxine) in terms of psychophysical assessments. In this randomised, double-blinded, placebo-controlled cross-over study, 20 healthy male participants (mean age: 24...
June 25, 2018: Basic & Clinical Pharmacology & Toxicology
Tuula Heinonen, Olavi Pelkonen, Hanna Tähti
European Consensus Platform for Alternatives (ecopa) and Scandinavian Society for Cell Toxicology (SSCT) hosted the joint ecopa-SSCT workshop "Up-to-date in vitro approaches in regulatory risk assessment and disease modeling" in Helsinki, 14-16 June 2017. The workshop consisted of three scientific sessions and poster sessions, all together 28 oral and 17 poster presentations. Further, a debate session on 'Human cellular or animal disease models: pros and cons to mimic human effects' was organized with Ian Cotgreave (Swetox, Sweden) and Matti Poutanen (University of Turku, Finland) as primary debaters to introduce opposing statements...
June 25, 2018: Basic & Clinical Pharmacology & Toxicology
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