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Basic & Clinical Pharmacology & Toxicology

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https://www.readbyqxmd.com/read/28429887/effects-of-aluminium-on-long-term-memory-in-rats-and-on-sirt1-mediating-the-transcription-of-creb-dependent-gene-in-hippocampus
#1
Dongying Yan, Cuihong Jin, Yang Cao, Lulu Wang, Xiaobo Lu, Jinghua Yang, Shengwen Wu, Yuan Cai
Epidemiological investigations have shown that aluminium (Al) is an important neurotoxicant which can be absorbed by organisms via various routes. Previous studies have confirmed that exposure to Al could cause neurodegenerative diseases, decline CREB phosphorylation and then down-regulate the transcription and protein expression of its target genes including BDNF. However, recent studies revealed that CREB activation alone was far from enough to activate the expression of long-term memory (LTM) related genes; there might be other regulatory factors involved in this process...
April 21, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28419737/a-10-year-experience-of-therapeutic-drug-monitoring-tdm-of-linezolid-in-a-hospital-wide-population-of-patients-receiving-conventional-dosing-is-there-enough-evidence-for-suggesting-tdm-in-the-majority-of-patients
#2
Federico Pea, Pier Giorgio Cojutti, Massimo Baraldo
A retrospective study was conducted to assess our 10-year experience of therapeutic drug monitoring (TDM) of linezolid in a large patient population to establish whether conventional dosing may result in adequate drug exposure in the majority of patients. Patients included in this study underwent TDM of linezolid trough concentration (Cmin ) during treatment with conventional doses of 600 mg every 12 hr in the period between January 2007 and June 2016. The desired range of Cmin was set between 2 and 7 mg/L (under-exposure, Cmin < 2 mg/L; over-exposure, Cmin > 7 mg/L)...
April 17, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28397349/therapeutic-drug-monitoring-of-venlafaxine-in-an-everyday-clinical-setting-analysis-of-age-sex-and-dose-concentration-relationships
#3
Morten Rix Hansen, Ida Berglund Kuhlmann, Anton Pottegård, Per Damkier
Venlafaxine is a commonly used antidepressant agent. We aimed to provide detailed information on the associations between venlafaxine dose and concentrations of venlafaxine, by patient age and sex. From a therapeutic drug monitoring (TDM) database located at Odense University Hospital, Denmark, we identified all adults for whom the treating physician had requested clinical advice on the TDM result for venlafaxine between 2002 and 2012. We identified 1,077 TDM samples of venlafaxine from 334 males and 743 females (median age 45 years), and the median daily dose was 225 mg...
April 11, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28374982/angiotensin-ii-receptor-blockers-inhibit-the-generation-of-epoxyeicosatrienoic-acid-from-arachidonic-acid-in-recombinant-cyp2c9-cyp2j2-and-human-liver-microsomes
#4
Asuna Senda, Yuji Mukai, Toru Hayakawa, Yuka Kato, Erik Eliasson, Anders Rane, Takaki Toda, Nobuo Inotsume
Cytochrome P450 (CYP) 2C9, CYP2C8 and CYP2J2 enzymes, which metabolize arachidonic acid to epoxyeicosatrienoic acids (EETs), have cardioprotective effects including anti-inflammation and vasodilation. We have recently shown that some angiotensin II receptor blockers (ARBs) may inhibit AA metabolism via CYP2C8. Using recombinant CYP2C9, CYP2J2, and human liver microsomes (HLMs), the aim was now to compare the ability of six different clinically used ARBs to inhibit AA metabolism in vitro. The rank order of the ARBs for the 50% inhibitory concentration (IC50 ) of AA metabolism was losartan < telmisartan < irbesartan < candesartan < olmesartan < valsartan via CYP2C9, and telmisartan < irbesartan < olmesartan < losartan < candesartan and valsartan via CYP2J2...
April 4, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28374979/matrix-metalloproteinase-mmp-2-activity-is-associated-with-divergent-regulation-of-calponin-1-in-conductance-and-resistance-arteries-in-hypertension-induced-early-vascular-dysfunction-and-remodelling
#5
Juliana M Parente, Camila A Pereira, Gustavo H Oliveira-Paula, José Eduardo Tanus-Santos, Rita C Tostes, Michele M Castro
Matrix metalloproteinase (MMP)-2 participates in hypertension-induced maladaptive vascular remodelling by degrading extra and intracellular proteins. The consequent extracellular matrix rearrangement and phenotype switch of vascular smooth muscle cells (VSMC) lead to increased cellular migration and proliferation. As calponin-1 degradation by MMP-2 may lead to VSMC proliferation during hypertension, the hypothesis of this study is that increased MMP-2 activity contributes to early hypertension-induced maladaptive remodelling in conductance and resistance arteries via regulation of calponin-1...
April 4, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28374976/ppar%C3%AE-activation-suppresses-cytochrome-p450-induction-potential-in-mice-treated-with-gemfibrozil
#6
Cunzhong Shi, Luo Min, Julin Yang, Manyun Dai, Danjun Song, Huiying Hua, Gangming Xu, Frank J Gonzalez, Aiming Liu
Gemfibrozil, a peroxisome proliferator-activated receptor α (PPARα) agonist, is widely used for hypertriglyceridaemia and mixed hyperlipidaemia. Drug-drug interaction of gemfibrozil and other PPARα agonists has been reported. However, the role of PPARα in Cytochrome P450 (CYP) induction by fibrates is not well known. In this study, wild-type mice were first fed gemfibrozil-containing diets (0.375%, 0.75% and 1.5%) for 14 days to establish a dose-response relationship for CYP induction. Then, wild-type mice and Pparα-null mice were treated with a 0...
April 4, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28374975/enrichment-of-genetic-variants-in-the-glucocorticoid-receptor-signalling-pathway-in-autoimmune-hepatitis-with-failure-of-standard-treatment
#7
Peter Lykke Eriksen, Martin Kreutzfeldt, Henning Grønbaek, Kasper Thorsen, Søren Vang, Niels Jessen, Hendrik Vilstrup
The standard treatment for autoimmune hepatitis (AIH) is predniso(lo)ne for remission induction, tapered and followed by azathioprine, which effectively controls the disease in the majority of patients. However, some patients prove to be unresponsive or non-tolerant and require alternative immunosuppressive regimens for disease control. We aimed to investigate whether these AIH patients who experience failure of standard treatment have a genomic basis for their problem in the form of pharmacogenetic variants...
April 4, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28374974/mathematical-modelling-of-glucose-dependent-insulinotropic-polypeptide-and-glucagon-like-peptide-1-following-ingestion-of-glucose
#8
Rikke M Røge, Jonatan I Bagger, Oskar Alskär, Niels R Kristensen, Søren Klim, Jens J Holst, Steen H Ingwersen, Mats O Karlsson, Filip K Knop, Tina Vilsbøll, Maria C Kjellsson
The incretin hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), play an important role in glucose homeostasis by potentiating glucose-induced insulin secretion. Furthermore, GLP-1 has been reported to play a role in glucose homeostasis by inhibiting glucagon secretion and delaying gastric emptying. As the insulinotropic effect of GLP-1 is preserved in patients with type 2 diabetes (T2D), therapies based on GLP-1 have been developed in recent years, and these have proven to be efficient in the treatment of T2D...
April 4, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28374970/human-bj-fibroblasts-is-an-alternative-to-mouse-balb-c-3t3-cells-in-in-vitro-neutral-red-uptake-assay
#9
Marika Mannerström, Tarja Toimela, Jertta-Riina Sarkanen, Tuula Heinonen
The OECD GD 129 BALB/c 3T3 Neutral Red Uptake (NRU) assay is a standardized test method for estimating starting dose for an acute oral systemic toxicity test in rodents. Mouse BALB/c 3T3 fibroblasts are the most commonly used cells in the NRU assay. We have previously transferred and validated BALB/c 3T3 NRU assay in our GLP laboratory. Subsequently, in order to obtain more human relevant cytotoxicity data, we performed an intra-laboratory validation using human BJ fibroblasts in the NRU assay instead of mouse BALB/c 3T3 fibroblasts...
April 4, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28374966/apoptosis-dysbiosis-and-expression-of-inflammatory-cytokines-are-sequential-events-in-the-development-of-5-fluorouracil-induced-intestinal-mucositis-in-mice
#10
Nahla Hamouda, Tatsushi Sano, Yosuke Oikawa, Toru Ozaki, Masaki Shimakawa, Kenjiro Matsumoto, Kikuko Amagase, Kazuhide Higuchi, Shinichi Kato
The chemotherapeutic agent 5-fluorouracil (5-FU) causes intestinal mucositis with severe diarrhoea but the pathogenesis is not fully understood. In the present study, we investigated the pathogenic effects of 5-FU in mice, focusing on apoptosis, enterobacteria and inflammatory cytokines. Repeated administration of 5-FU caused severe intestinal mucositis on day 6, accompanied by diarrhoea and body weight loss. TNF-α expression increased one day after exposure to the drug, and spiked a second time on day 4, at which point myeloperoxidase activity and IL-1β expression also increased...
April 4, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28374942/comparative-analysis-of-the-suspected-heparin-induced-thrombocytopenia-level-in-korea
#11
Hun-Sung Kim, Hyunah Kim, Yoo Jin Jeong, Hyunyong Lee, Hyeon Woo Yim, Ji Il Kim, In Sung Moon, Jang-Yong Kim
The primary objective of our study was to evaluate the frequency of suspected heparin-induced thrombocytopenia (HIT) among patients treated with different formulations of heparin and investigate the factors that affect the incidence of HIT. This study is an electronic medical record (EMR)-based large-scale retrospective cohort study conducted from 2009 to 2014 in Korea. After hospitalization, patient platelet count was determined before heparin was prescribed, and all platelet count values obtained during hospitalization were extracted...
April 4, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28371398/targeting-tankyrase-to-fight-wnt-dependent-tumours
#12
Tor Espen Thorvaldsen
Aberrant WNT signalling activity is linked to various diseases due to the WNT dependency of fundamental processes during development and in adult tissue homeostasis. Mutations in components of the multiprotein β-catenin destruction complex promote excessive amounts of the main transcriptional activator β-catenin and are particularly common in colorectal cancer (CRC). The tankyrase enzymes were recently implicated as negative regulators of destruction complex activity by mediating degradation of the scaffolding protein AXIN...
April 2, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28371382/inhibitory-effects-of-urothelium-related-factors
#13
Na N Guan, Lars E Gustafsson, Karl Svennersten
The urothelium of the bladder has long been recognized as a protective barrier between detrusor and urine. In recent years, it has become more evident that the urothelium plays a role as an active source of mediators. The urothelium can release neurotransmitters and modulators such as acetylcholine, ATP, nitric oxide, prostaglandins and neuropeptides. They exert both excitatory and inhibitory effects in modulating urinary tract motility. In addition, several studies have reported the existence of an urothelium-derived unknown inhibitory factor in the urinary bladder...
April 2, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28371247/ivabradine-current-and-future-treatment-of-heart-failure
#14
Lene Thorup, Ulf Simonsen, Daniela Grimm, Elise Røge Hedegaard
In heart failure (HF), the heart cannot pump blood efficiently and is therefore unable to meet the body's demands of oxygen, and/or there is increased end diastolic pressure. Current treatments for heart failure with reduced ejection fraction (HFrEF) include angiotensin-converting enzyme (ACE)-inhibitors, angiotension receptor type 1 (AT1 ) antagonists, β-adrenoceptor-antagonists, aldosterone receptor antagonists, diuretics, digoxin and a combination drug with AT1 receptor antagonist and neprilysin inhibitor...
April 2, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28371342/essential-medicines-list-implementation-dynamics-a-case-study-using-brazilian-federal-medicines-expenditures
#15
Rachel Magarinos-Torres, Larry David Lynd, Tatiana Chama Borges Luz, Paulo Eduardo Potyguara Coutinho Marques, Claudia Garcia Serpa Osorio-de-Castro
The aim was to analyse the implementation dynamics of the Essential Medicines List (EML). We used the government expenditures on medicines and Brazil as a case study. Drug purchases were considered as a proxy for utilization. The essential medicines (EMs) expenditures were followed over time by Brazilian National EMLs lifetime and defined by broad therapeutic categories and by specific medicines. Brazil increased the number of the EMs during the last four editions of your Brazilian National EMLs and the federal government expenditures on them...
March 29, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28371296/population-exposure-to-phthalate-containing-drugs
#16
Anne Broe, Zandra Nymand Ennis, Anton Pottegård, Jesper Hallas, Thomas Ahern, Per Damkier
Phthalates are known endocrine disruptors. Not commonly recognised, phthalates are used as excipients in a number of drug formulations. We aimed to describe the sale of phthalate-containing drugs in Denmark from 2004 to 2015. National data on annual sale of medications (tablets only) were accessed from medstat.dk. Data from the Danish Medicines Agency on phthalate content per tablet were merged with data on total sale for each active substance and drug formulation. We used the 'defined daily dose' (DDD) as the unit of sale and calculated the total amount of phthalate (mg) dispensed per 1,000 inhabitants...
March 29, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28371123/effects-of-nano-graphene-oxide-on-testis-epididymis-and-fertility-of-wistar-rats
#17
Naresh Kumar Nirmal, Kumud Kant Awasthi, Placheril Joseph John
Nanoscale graphene oxide (NGO) has great potential in biomedicine by the virtue of its facile functionalization and tunable characteristics. Toxicity assessments have, therefore, become essential prior to its biomedical applications. The present study examined the effects of NGO exposure on male reproductive function of adult Wistar rats. Rats were exposed intraperitoneally to three increasing doses, namely low (0.4 mg/kg BW), mid (2.0 mg/kg BW) and high (10.0 mg/kg BW) dose of NGO. Repeated exposure of NGO for 15 and 30 days resulted in decreased epididymal sperm counts and elevated sperm abnormalities...
March 29, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28326680/the-effect-of-desmopressin-on-the-amount-of-bleeding-and-transfusion-requirements-in-patients-undergoing-heart-transplant-surgery
#18
Alireza Jahangirifard, Mohammad Reza Razavi, Zargham Hosein Ahmadi, Mohammad Forozeshfard
One of the most common risks after a heart transplant is bleeding. In this study, the effect of desmopressin administration on the amount of bleeding and transfusion requirements following heart transplant surgery was investigated. In a double-blind clinical trial, 48 patients who were candidates for heart transplant surgery were randomly assigned to two groups. In the intervention group, patients received desmopressin 0.3 μg/kg, 30 min. before surgery. Patients in the control group received normal saline at the same amount and time...
March 22, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28317271/baclofen-and-alcohol-dependent-patients-a-real-risk-of-severe-self-poisoning
#19
David Boels, Caroline Victorri-Vigneau, Marie Grall-Bronnec, Ali Touré, Anais Garnier, Alain Turcant, Gaël Le Roux
Baclofen is often prescribed in high doses to fight cravings experienced by alcohol-dependent patients. Such an increase in the availability of baclofen is concerning. This study aimed to determine the change in number and profile of self-poisoning with baclofen over time, since baclofen has become increasingly popular, in order to describe the severity of self-poisoning with baclofen and to focus on co-existing alcohol use disorders and psychiatric illnesses determine predictors of severity. This was a retrospective study of self-poisoning with baclofen as reported by the western France Poison Control Center (PCC), which represents a population of more than 12 million people from January 2008 to March 2014...
March 19, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28299900/development-of-a-robust-mammalian-cell-based-assay-for-studying-recombinant-%C3%AE-4-%C3%AE-1-3-%C3%AE-gabaa-receptor-subtypes
#20
Christina B Falk-Petersen, Rikke Søgaard, Kenneth L Madsen, Anders B Klein, Bente Frølund, Petrine Wellendorph
δ-Containing GABAA receptors are located extrasynaptically and mediate tonic inhibition. Their involvement in brain physiology positions them as interesting drug targets. There is thus a continued interest in establishing reliable recombinant expression systems for δ-containing GABAA receptors. Inconveniently, the recombinant expression of especially α4 β1/3 δ receptors has been found to be notoriously difficult, due to mixed receptor populations and/or stoichiometries and differential pharmacology depending on the expression system used...
March 16, 2017: Basic & Clinical Pharmacology & Toxicology
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