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Basic & Clinical Pharmacology & Toxicology

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https://www.readbyqxmd.com/read/28889650/correlation-of-recommendations-of-treatment-guidelines-and-frequently-prescribed-antibiotics-evaluation-of-their-pharmaceutical-pack-size
#1
Shoma Mukherjee, Nilanjan Saha
There are various factors that contribute to development of antimicrobial resistance. Overuse, inappropriate prescribing and extensive agricultural use of antibiotics are some of the factors which have been identified. Antibiotics are almost always universally packaged by manufacturers in packs that are heavily driven by cost of economies and convenience rather than by any scientific basis or duration of therapy. So, in the present study, the correlation of the treatment guidelines with the choice of antibiotics and whether packing size contributes to left-over dosing units when used according to guideline recommendations were assessed...
September 10, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28889522/salidroside-a-chemopreventive-glycoside-diminishes-cytotoxic-effect-of-cisplatin-in-vitro
#2
Martina Zduriencikova, Dana Cholujova, Jozef Duraj, Maria Mastihubova, Vladimir Mastihuba, Elena Karnisova Potocka, Eliska Galova, Andrea Sevcovicova, Martina Klapakova, Eva Horvathova
Natural products represent the source or the inspiration for the majority of the active ingredients of medicines because of their structural diversity and a wide range of biological effects. Our aims in this study were (i) to synthesize enzymatically salidroside (SAL), the most effective phenylethanoid glycoside in Rhodiola species; (ii) to examine its antioxidant capacity using cell-free assays (reducing power, DPPH radicals scavenging and Fe(2+) -chelating assays); (iii) to assess its DNA-protective potential on plasmid DNA (DNA topology assay) and in HepG2 cells (comet assay) damaged by Fe(2+) ions and hydrogen peroxide, respectively; and (iv) to investigate the effects of SAL, cisplatin (CDDP) and combined treatments of SAL + CDDP on cell viability (MTT test), level of DNA damage (comet assay), proliferation, cell cycle (flow cytometry) and the expression of signalling molecules associated with cell growth and apoptotic pathways (western immunoblotting)...
September 10, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28887828/opportunities-for-students-to-prescribe-an-evaluation-of-185-consultations-in-the-student-run-cardiovascular-risk-management-programme
#3
Tim Schutte, Katinka Prince, Milan Richir, Erik Donker, Leonie van Gastel, Ferdynand Bastiaans, Henk de Vries, Jelle Tichelaar, Michiel van Agtmael
Involving students in CVRM could offer patients a structured CVRM programme and students a valuable learning opportunity. We describe and evaluate a student-run CVRM programme that was set up to offer primary prevention to patients with known risk factors in a general practitioner's practice. During a consultation, two undergraduate medical students assessed the patients' actual risk and formulated a CVRM plan, which they discussed with the patient after approval by a GP. After the consultations, patients were asked to complete evaluation/feedback questionnaires...
September 9, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28881461/overdoses-with-aripiprazole-signs-symptoms-and-outcomes-in-239-exposures-reported-to-the-danish-poison-information-center
#4
Amalie P Christensen, Soeren Boegevig, Mikkel B Christensen, Kasper M Petersen, Kim P Dalhoff, Tonny S Petersen
The aim of this study was to characterize the clinical signs and symptoms of exposures to aripiprazole overdoses. We retrospectively identified all aripiprazole exposures reported to the Danish Poisons Information Center (DPIC) from June 2007 to May 2015. Information concerning demographics, ingested dose and symptoms were extracted from the DPIC database and medical records. Information on death and admission to hospital was obtained from Danish national registers. We analysed 239 cases, 86 concerning single-drug exposures to aripiprazole, and 153 cases where aripiprazole had been taken with at least one other substance (mixed-drug)...
September 7, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28881079/formyl-peptide-receptors-in-mice-and-men-similarities-and-differences-in-recognition-of-conventional-ligands-and-modulating-lipopeptides
#5
Malene Winther, Claes Dahlgren, Huamei Forsman
The pattern recognition formyl peptide receptors (FPRs) belong to the class of G protein-coupled receptors (GPCRs), the largest group of cell-surface receptors involved in a range of physiological processes and pathologies. The FPRs have regulatory function in the initiation as well as resolution of inflammatory reactions, making them highly interesting as targets for drug development. Recent research in the GPCR/FPR fields has uncovered novel receptor biology concepts, including biased signalling/functional selectivity, allosteric modulation, receptor reactivation and receptor cross-talk...
September 7, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28871627/important-aspects-of-pharmacist-led-medication-reviews-in-an-acute-medical-ward
#6
Cille Bülow, Kirstine Ullitz Faerch, Helle Armandi, Birgitte Nybo Jensen, Jesper Sonne, Hanne Rolighed Christensen, Mikkel Christensen
In some hospitals, clinical pharmacists review the medication to find drug-related problems (DRPs) in acutely admitted patients. We aimed to identify the nature of identified DRPs and investigate factors of potential importance for the clinical implementation of pharmacist suggestions. In 100 randomly selected medication review notes, we retrospectively evaluated the clinical implementation and classified 1) timing and communication of the review; 2) DRPs and related suggestions for the physician; and 3) DRPs' potential clinical relevance to patients as 'beneficial', 'somewhat beneficial', 'no relevance' or 'other relevance'...
September 4, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28869786/population-pharmacokinetic-pharmacodynamic-modelling-of-auditory-evoked-event-related-potentials-with-lorazepam
#7
Aurélie Lombard, Claire Brittain, Graham Wishart, Stephen Lowe, Andrew McCarthy, William Landschulz, Georg Dorffner, Peter Anderer, Eunice Yuen
Event-Related Potentials (ERPs) are commonly used in Neuroscience research, particularly the P3 waveform because it is associated with cognitive brain functions and is easily elicited by auditory or sensory inputs. ERPs are affected by drugs such as lorazepam, which increase the latency and decrease the amplitude of the P3 wave. In this study, auditory-evoked ERPs were generated in 13 older healthy volunteers using an oddball tone paradigm, after administration of single 0.5 and 2mg doses of lorazepam. Population pharmacokinetics (PK)/ pharmacodynamics (PD) models were developed using non-linear mixed effects methods in order to assess the effect of lorazepam on the latency and amplitude of the P3 waveforms...
September 4, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28862803/patient-and-cell-type-specific-heterogeneity-of-metformin-response
#8
Michael K Asiedu, Matthew Barron, Marie Christine Aubry, Dennis A Wigle
Most FDA approved drugs are not equally effective in all patients, suggesting that identification of biomarkers to predict responders to a chemoprevention agent will be needed to stratify patients and achieve maximum benefit. The goal of this study was to investigate both patient-specific and cell-context-specific heterogeneity of metformin response, using fibroblast cell lines and induced pluripotent stem cells differentiated into lung epithelial lineages. We performed cell survival analysis, transcriptome and whole exome sequencing analysis on both patient-derived cell lines and cancer cell lines to assess differential metformin response and identify response genes...
September 1, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28862800/neurological-and-neurophysiological-findings-in-workers-with-chronic-2-3-7-8-tcdd-intoxication-50-years-after-exposure
#9
Daniela Pelclova, Pavel Urban, Zdenka Fenclova, Stepanka Vlckova, Petr Ridzon, Karel Kupka, Zuzana Meckova, Ondrej Bezdicek, Tomas Navratil, Jan Rosmus, Sergey Zakharov
The last eight survivors of 80 workers accidentally exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during production of herbicides based on trichlorophenoxyacetic acid in 1965-1967 in a chemical factory were followed. All were men, mean age 72.4 ± 1.3 years. Their current median TCDD blood level was 112 (46-390) pg/g lipids. Neurological examination revealed central nervous system impairment in all subjects, and signs of polyneuropathy in 87.5%, which was confirmed by a nerve conduction study (NCS) in 75%...
September 1, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28857508/systemic-tlr2-antibody-application-in-renal-ischaemia-and-reperfusion-injury-decreases-akt-phosphorylation-and-increases-apoptosis-in-the-mouse-kidney
#10
Anja Urbschat, Patrick Baer, Kai Zacharowski, Vera Sprunck, Bertram Scheller, Florian Raimann, Thorsten Jürgen Maier, Axel Hegele, Rainer Hofmann, Jan Mersmann
Acute kidney injury remains an important cause of renal dysfunction. In this context, toll-like receptors have been demonstrated to play a critical role in the induction of innate and inflammatory responses. Among these, toll-like receptor 2 (TLR2) is constitutively expressed in tubular epithelial cells of the kidney and is also known to mediate ischaemia reperfusion (IR) injury. Adult male C57BL/6JRj mice were randomized into 7 groups (n=8): A non-operative control group (CTRL) and 6 interventional groups in which mice were subjected to a 30-min...
August 30, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28857484/bisphenol-a-exposure-impairs-epididymal-development-during-the-peripubertal-period-of-rats-inflammatory-profile-and-tissue-changes
#11
Fernanda Mithie Ogo, Glaucia Eloisa Munhoz de Lion Siervo, Larissa Staurengo-Ferrari, Leonardo de Oliveira Mendes, Nicla Renata Luchetta, Henrique Rodrigues Vieira, Victor Fattori, Waldiceu Aparecido Verri, Wellerson Rodrigo Scarano, Glaura Scantamburlo Alves Fernandes
Bisphenol A (BPA) is a synthetic non-steroidal oestrogen used in the production of plastics. BPA can cause alterations in the endocrine system of humans and animals at varied stages of development. During puberty, altered morphological, sexual behaviour and completion of the epididymal development occurs. Therefore, this study aimed to evaluate the effects of BPA on epididymal development during the peripubertal period of rats. Male Wistar rats were treated with BPA via gavage at doses of 20 μg/kg or 200 μg/kg/day (postnatal day (PND) 36-66)...
August 30, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28843027/lc-ms-smrm-method-development-and-validation-of-different-classes-of-pain-panel-drugs-and-analysis-of-clinical-urine-samples
#12
M Athar Masood, Timothy D Veenstra
Urine Drug Testing (UDT) is an important analytical/bio-analytical technique that has inevitably become an integral and vital part of a testing program for diagnostic purposes. This manuscript presents a tailor-made LC-MS/MS quantitative assay method development and validation for a custom group of 33 pain panel drugs and their metabolites belonging to different classes (opiates, opioids, benzodiazepines, illicit, amphetamines, etc.) that are prescribed in pain management and depressant therapies. The LC-MS/MS method incorporates two experiments to enhance the sensitivity of the assay and has a run time of about 7 min...
August 26, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28842957/understanding-epigenetic-effects-of-endocrine-disrupting-chemicals-from-mechanisms-to-novel-test-methods
#13
Ali Alavian-Ghavanini, Joëlle Rüegg
Endocrine disrupting chemicals (EDCs) are man-made chemicals that interfere with hormonal signalling pathways. They are used in, e.g., production of common household materials, in resin-based medical supplies, pesticides. Thus, they are environmentally ubiquitous and humans and wildlife are exposed to them on a daily basis. Early life exposure to EDCs has been associated with later life adversities such as obesity, diabetes and cancer. Mechanisms underlying such associations are unknown but are likely to be mediated by epigenetic changes induced by EDCs...
August 26, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28834230/renal-impairment-hampers-bisphosphonate-treatment-in-a-quarter-of-lung-cancer-patients-with-bone-metastasis
#14
Katalin Fábián, Rita Puskás, Tímea Kakuk, László Prés, Dorottya Fejes, Zsolt Szegedi, Lívia Rojkó, Zoltán Szállási, Balázs Döme, Orsolya Pipek, Judit Moldvay
Renal function impairment in lung cancer patients with bone metastases was investigated, as this can limit the application of bisphosphonates representing the gold standard in the management of such cases. Clinicopathological data of 570 lung cancer patients were retrospectively analysed for changes in renal function parameters. Co-morbidities included hypertension (50%), COPD (33%) and diabetes mellitus (15%). Statistical analysis was performed with Fisher's exact tests and a Cox proportional hazards model...
August 21, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28834135/the-pharmacogenetics-of-metformin-in-women-with-pcos-a-randomized-trial
#15
Andreas J T Pedersen, Tore Bjerregaard Stage, Dorte Glintborg, Marianne Andersen, Mette Marie Hougaard Christensen
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting women of reproductive age. PCOS is associated with obesity, dyslipidaemia and insulin resistance, and metformin treatment may improve such metabolic features. The effect of genetic variants in key metformin transporters, their transcriptional regulators or in metformin target genes on metformin response in women with PCOS is unclear. Associations between pharmacodynamic responses to metformin (changes in weight, lipid profile, insulin sensitivity evaluated by oral glucose tolerance testing) and polymorphisms in OCT1 (rs12208357 and rs72552763), HNF1A (rs1169288 and rs2464196), MATE1 (rs2289669 and rs2252281), MATE2-K (rs12943590) and ATM (rs11212617) were studied in 40 women with PCOS randomized to 12 months of treatment with metformin 1000 mg twice daily ± oral contraceptive pills (150 mg desogestrel + 30 μg ethinylestradiol)...
August 21, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28834212/assessment-of-appropriateness-of-an-initial-dosing-regimen-of-vancomycin-and-development-of-a-new-dosing-nomogram
#16
Seonghae Yoon, Kyoung Ryun Park, SeungHwan Lee, Sang-Hoon Song, Wan Beom Park, In-Jin Jang, Kyung-Sang Yu
Vancomycin is a glycopeptide antibiotic used to treat Gram-positive infections including methicillin-resistant Staphylococcus aureus (MRSA). The objectives of this study were to evaluate the appropriateness of the initial dosing regimen of vancomycin, identify factors to be considered in regimen selection and develop a new dosing nomogram. Therapeutic drug monitoring (TDM) data of vancomycin obtained from Seoul National University Hospital from 2011 to 2013 were included in this analysis. The vancomycin trough concentrations at steady state were estimated using Abbott's PKS software program and then categorized into three levels: subtherapeutic, therapeutic and toxic...
August 20, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28834189/evaluation-of-post-mortem-effects-on-global-brain-dna-methylation-and-hydroxymethylation
#17
Louise K Sjöholm, Yusuf Ransome, Tomas J Ekström, Oskar Karlsson
The number of epigenetic studies on brain functions and diseases are dramatically increasing but little is known about the impact of post-mortem intervals and post-sampling effects on DNA modifications such as 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). Here, we examined post-mortem induced changes in global brain 5mC and 5hmC levels at post-mortem intervals up to 540 min., and studied effects of tissue heat stabilization, by using LUMA and ELISA. The global 5mC and 5hmC levels were generally higher in the cerebellum of adult rats than neonates...
August 20, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28816009/protective-effect-of-atazanavir-sulfate-against-pulmonary-fibrosis-in-vivo-and-in-vitro
#18
Shina Song, Yunxia Ji, Guanghua Zhang, Xue Zhang, Bin Li, Defang Li, Wanglin Jiang
Atazanavir sulfate, an antiretroviral protease inhibitor, has been used to treat HIV/AIDS, but its ability to serve as an anti-pulmonary fibrosis (PF) agent remains unknown. In this study, the effects of atazanavir sulfate on various aspects of PF were examined and CoCl2 was used to induce the hypoxia-mimicking condition in vitro, including epithelial-mesenchymal transition (EMT) in A549 cells, endothelial-mesenchymal transition (EndMT) in human pulmonary microvascular endothelial cells (HPMECs), proliferation in human lung fibroblasts (HLF-1) and potential protective effects in human type I alveolar epithelial cells (AT I)...
August 16, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28815909/proximal-neuropathy-and-associated-skeletal-muscle-changes-resembling-denervation-atrophy-in-hind-limbs-of-chronic-hypoglycaemic-rats
#19
Vivi F H Jensen, Anne-Marie Molck, Henrik Soeborg, Jette Nowak, Melissa Chapman, Jens Lykkesfeldt, Ingrid B Bogh
Peripheral neuropathy is one of the most common complications of diabetic hyperglycaemia. Insulin-induced hypoglycaemia (IIH) might potentially exacerbate or contribute to neuropathy as hypoglycaemia also causes peripheral neuropathy. In rats, IIH induces neuropathy associated with skeletal muscle changes. Aims of the present study were to investigate the progression and sequence of histopathologic changes caused by chronic IIH in rat peripheral nerves and skeletal muscle, and whether such changes were reversible...
August 16, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28805311/mechanistic-model-for-blood-pressure-and-heart-rate-changes-produced-by-telmisartan-in-humans
#20
Dong Woo Chae, Mijeong Son, Yukyung Kim, Hankil Son, Kyungsoo Park
Telmisartan, an angiotensin receptor blocker (ARB), is indicated for the treatment of essential hypertension. This study aimed to develop a mechanistic model of telmisartan drug effect in human using non-invasive markers. Data were acquired from a previous study where telmisartan 80 mg was given once daily for 6 days. Systolic (SBP) and diastolic blood pressure (DBP) and heart rate (HR) were measured before dosing for day 1 to 5 and serially after the last dose. Mean arterial pressure (MAP) and pulse pressure (PP) were calculated from SBP and DBP...
August 14, 2017: Basic & Clinical Pharmacology & Toxicology
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