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Fundamental & Clinical Pharmacology

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https://www.readbyqxmd.com/read/29319893/possible-role-of-cyp2b6-genetic-polymorphisms-in-ifosfamide-induced-encephalopathy-report-of-three-cases
#1
Thomas Duflot, Aude Marie-Cardine, Céline Verstuyft, Bruno Filhon, Tony Pereira, Nathalie Massy Guillemant, Robinson Joannidès, Jérémy Bellien, Fabien Lamoureux
Ifosfamide (IFA) is a potent alkylating antitumoral agent but its use is limited by neurological side effects. IFA is a racemic mixture of two enantiomeric forms, R-IFA and S-IFA with a stereoselective metabolism by CYP3A4 and CYP2B6, leading either to bioactive or to toxic pathways. In 3 consecutive cases of pediatric patients who exhibited ifosfamide-induced encephalopathy (IIE), genotyping of clinically relevant single nucleotide polymorphisms associated with decreased CYP3A4 and CYP2B6 activities was performed...
January 10, 2018: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/29315849/continuous-intravenous-vancomycin-in-children-with-normal-renal-function-hospitalized-in-hematology-oncology-prospective-validation-of-a-dosing-regimen-optimizing-steady-state-concentration
#2
Delphine Hoegy, Sylvain Goutelle, Nathalie Garnier, Cécile Rénard, Cécile Faure-Conter, Christophe Bergeron, Yves Bertrand, Nathalie Bleyzac
Continuous intravenous (IV) infusion has been shown to be the best option to administer vancomycin because of its time-dependent bactericidal activity. Available IV vancomycin dosing guidelines in pediatrics with normal renal function leads to less than 50% of patients achieving a vancomycin serum concentration (Css) in the target range (15 to 20 mg/l). The primary objective of this study was to prospectively validate an age-based dosing regimen in pediatric onco-hematology. The secondary objective was to investigate the influence on Css attainment of different variables...
January 6, 2018: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/29314262/adverse-drug-reactions-of-analgesic-medicines-analysis-of-the-romanian-pharmacovigilance-database
#3
Irina Cazacu, Roxana Stroe, Roxana Dondera, Cristina Mogosan, Françoise Haramburu, Annie Fourrier-Réglat, Felicia Loghin
The results of national safety studies are essential for decision-making at the regulatory level and have also educational implications for prescribing patterns. The aim of the present study was to analyze the ADRs of analgesic medicines spontaneously reported to Pharmacovigilance and Risk Management Service of the Romanian National Agency for Medicines and Medical Devices between 2011 and 2015. For the 71 reports, patients had a mean age of 39.8 years; 60.6% of patients were female, 38% male and 1.4% were unknown...
January 4, 2018: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/29290096/protective-effect-of-fenofibrate-against-ischemia-reperfusion-induced-cardiac-arrhythmias-in-isolated-rat-hearts
#4
Ishfaq A Bukhari, Abdulrahman A Almotrefi, Osama Y Mohamed, Abeer A Al-Masri, Saeed Ahmed Sheikh
Fenofibrate is a peroxisome proliferator-activated receptor (PPAR)-α activator that lowers triglycerides and influences cytochrome P-450 (CYP-450) epoxygenase dependent arachidonic acid (AA) metabolism. CYP-450 epoxygenase metabolizes AA to epoxyeicosatrienoic acids (EETs). EETs have coronary dilating, cardiac and renal protective properties. Fibrates possess similar properties due to their CYP-450 epoxygenase inducing properties that leads to increase in endogenous EETs production. In the current investigations fenofibrate (100 mg/kg, orally) for two weeks decreased ischemia/reperfusion (I/R)-induced premature ventricular contractions (PVCs), ventricular tachycardia (VT) and ventricular fibrillation (VF) in the isolated rat hearts...
December 31, 2017: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/29239015/treating-hepatic-encephalopathy-in-cirrhotic-patients-admitted-to-icu-with-sodium-phenylbutyrate-a-preliminary-study
#5
Nicolas Weiss, Simona Tripon, Marion Lodey, Elsa Guiller, Helga Junot, Denis Monneret, Julien Mayaux, Hélène Brisson, Maxime Mallet, Marika Rudler, Françoise Imbert-Bismut, Dominique Thabut
Hepatic encephalopathy (HE) influences short and long-term prognosis. Recently, glycerol phenylbutyrate (PB), that lowers ammonia by providing an alternate pathway to urea for waste nitrogen excretion, has shown that it was effective in preventing the occurrence of HE in RCT. The aim was to assess the benefits of sodium PB in cirrhotic patients admitted in ICU for overt HE, in terms of ammonia levels decrease, neurological improvement and survival. Cirrhotic patients who presented with overt HE, ammonia levels >100 μmol/L, and did not display any contra-indication were included...
December 14, 2017: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/29224234/an-observational-study-of-benzodiazepine-prescription-during-inpatient-alcohol-detoxification-for-patients-with-versus-without-chronic-pretreatment-with-high-dosage-baclofen
#6
Laura Martinez, Florence Vorspan, Xavier Declèves, Julien Azuar, Maeva Fortias, Franck Questel, Alexandra Dereux, Leslie Grichy, Hélène Barreteau, Frank Bellivier, Jean-Pierre Lépine, Vanessa Bloch
High dose baclofen is prescribed as a maintenance treatment to reduce alcohol use in patients with alcohol use disorder. Nevertheless, some patients still have massive alcohol intakes and require inpatient alcohol withdrawal. AIM: to compare the oral dose of benzodiazepine prescribed to manage alcohol withdrawal symptoms in patients with versus without steady state pre-treatment with high dose baclofen. METHODS: Retrospective chart review study. Prescribed benzodiazepine dose expressed in diazepam-equivalent was compared between groups...
December 10, 2017: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/29206314/inhibition-of-spinal-p38-mapk-prevents-articular-neutrophil-infiltration-in-experimental-arthritis-via-sympathetic-activation
#7
Alexandre Kanashiro, Marcelo Franchin, Gabriel Shimizu Bassi, Dênis Augusto Reis-Santana, Thiago Mattar Cunha, Fernando Queiróz Cunha, Luis Ulloa, Gerson Jonathan Rodrigues
The central nervous system controls the innate immunity by modulating efferent neuronal networks. Recently, we have reported that central brain stimulation inhibits inflammatory responses. In the present study, we investigate whether spinal p38 mitogen-activated protein kinase (MAPK) affects joint inflammation in experimental arthritis. Firstly, we observed that intra-articular administration of zymosan in mice induces the phosphorylation of the spinal cord p38 MAPK. In addition, we demonstrated that spinal p38 MAPK inhibition with intrathecal injection of SB203580, a conventional and well-characterized inhibitor, prevents knee joint neutrophil recruitment, edema formation, experimental score and cytokine production...
December 5, 2017: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/29193274/melatonin-therapy-reduces-the-risk-of-osteoporosis-and-normalizes-bone-formation-in-multiple-sclerosis
#8
Majid Ghareghani, Linda Scavo, Damien Arnoult, Kazem Zibara, Naser Farhadi
Multiple sclerosis (MS) is a common autoimmune and neurodegenerative disease of the central nervous system. Serum levels of melatonin decrease in MS patients who are also at risk of osteoporosis. Procalcitonin (proCT) has been reported as a biomarker of systemic inflammation and autoimmune disease, however, its changes in MS patients has not been well explored. This study investigated, using ELISA, the clinical correlation between serum melatonin and proCT in MS patients. We then assessed the effect of melatonin (10mg/kg) therapy on bone metabolism and osteoporosis in experimental autoimmune encephalomyelitis (EAE) model of MS and in MS patients...
November 28, 2017: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/29172254/the-role-of-nonsteroidal-anti-inflammatory-drugs-nsaids-intramuscular-injection-in-the-development-and-severity-of-deep-soft-tissue-infection-in-mice
#9
Zeynep Ture, Hayati Demiraslan, Olgun Kontas, Emine Alp, Mehmet Doganay
The aim of this study was to determine the role of nonsteroidal anti-inflammatory drugs (NSAID) injection on the severity of local infection and the effect on the progression of soft tissue infection (STI).The mouse model of STI with Group A streptococcus (GAS) was developed and treated with diclofenac sodium (DS) intramuscularly. Mice were divided into 5 groups: administered DS for 48 hours before GAS (Group1), GAS-DS and maintained DS for 48 hours (Group 2), DS for 48 hours (Group 3), GAS on zero time (Group 4) and control (Group 5)...
November 24, 2017: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/29172244/comparative-study-of-amlodipine-versus-cilnidipine-for-the-prevention-of-hepatic-ischemia-reperfusion-injury-in-rat-model
#10
Abdel-Motaal M Fouda, Amany Ragab Youssef, Osama Sharaf Eldin
Ca(2+) signaling plays crucial role in ischemia and reperfusion (I/R) injury. Although blockade of L-type Ca(2+) channels by amlodipine (AML) has been shown to suppress hepatic I/R injury in several animal models, information is still needed regarding the hepatoprotective effects of the dual L/N-type CCB, cilnidipine (CIL). We examined the effect of pretreatment with AML or CIL (100 μg/kg i.p.) 45 min before induction of 60 min of liver ischemia followed by reperfusion, on oxidative stress markers, liver enzymes, serum tumor necrosis factor (TNF)-α, interleukin (IL)-1β, apoptosis markers, and nuclear factor KB (NF-κB) after 6 and 24 h of hepatic reperfusion...
November 24, 2017: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/29144574/sglt-2-inhibitors-and-ketoacidosis-a-disproportionality-analysis-in-the-world-health-organization-s-adverse-drug-reactions-database
#11
Abdel Nasser Ado Moumouni, Perrine Robin, Dominique Hillaire-Buys, Jean-Luc Faillie
SGLT-2 inhibitors, also called gliflozins, are a new class of drugs used in type 2 diabetes. Since their marketing, several cases of ketoacidosis, including life-threatening conditions, were reported with their use. The objective of this study was to investigate the disproportionality of pharmacovigilance reports of ketoacidosis between gliflozins and other drugs used for type 2 diabetes. We performed a case non-case study within the World Health Organization's pharmacovigilance database, VigiBase. We selected all reports of serious adverse drug reaction associated with a glucose-lowering drug in patients aged 40 years and older, from January 2013 to March 2016...
November 16, 2017: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/29143369/detection-of-adverse-drug-reactions-evaluation-of-an-automatic-data-processing-applied-in-oncology-performed-in-the-french-drg-database
#12
Alexandre Quillet, Olivier Colin, Nicolas Bourgeois, Sylvie Favrelière, Aurélie Ferru, Laurence Boinot, Claire Lafay-Chebassier, Marie-Christine Perault-Pochat
The aim of this study was to assess an automated detection method of serious adverse reactions induced by oral targeted therapy (OTT) in patients with cancer, performed in the French Diagnosis Related Groups (DRG) database. Cancer patients of the Poitiers hospital who started an OTT between 2014 and 2015 were included. This study focused on adverse drug reaction which required inpatient hospitalization (ADRh ). All diagnoses coded in the DRG database for hospital stays that occurred within three months after OTT initiation were collected (potential ADRh )...
November 15, 2017: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/29143356/on-the-ground-application-of-the-temporary-recommendation-for-use-regulatory-measure-on-off-label-use-of-baclofen-for-alcohol-dependence-in-france-a-regional-survey-of-community-pharmacies
#13
Marine Auffret, Benjamin Rolland, Anne-Sylvie Caous, Louise Gaboriau, Sylvie Deheul, Régis Bordet, Sophie Gautier
The "temporary recommendation for use" (TRU) is a French novel regulatory measure for off-label drug. The first TRU to be issued by the French drug agency (in March 2014) pertained to the off-label use of baclofen for alcohol dependence (AD). We performed a questionnaire-based survey of the on-the-ground application of the baclofen TRU among community pharmacies in northern France. A pharmacist from 70 of the 219 pharmacies contacted (response rate: 32.0%) completed the questionnaire. The mean ± standard deviation number of off-label baclofen prescriptions for AD was 2...
November 15, 2017: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/29125648/pharmacological-effects-of-zataria-multiflora-boiss-l-and-its-constituents-focus-on-their-anti-inflammatory-antioxidant-and-immunomodulatory-effects
#14
REVIEW
Mohammad Reza Khazdair, Vahideh Ghorani, Azam Alavinezhad, Mohammad Hossein Boskabady
Zataria multiflora Boiss (Z. multiflora) belongs to the Lamiaceae family, is used traditionally for culinary and medicinal purposes. Different pharmacological effects have been described for the plant including; bronchodilation, vasodilation and effect on lung inflammation. The plant is also used as a remedy against cough in the traditional medicine. In this article, "pharmacological effects of Z. multiflora and its constituents focusing on their anti-inflammatory, antioxidant and immunomodulatory properties were reviewed" by searching various databases until "June" 2016...
November 10, 2017: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/29091319/population-pharmacokinetics-of-oral-baclofen-at-steady-state-in-alcoholic-dependent-adult-patients
#15
Lucie Chevillard, Naomi Sabo, Michel Tod, Laurence Labat, Céline Chasport, Céline Chevaleyre, Florence Thibaut, Jérôme Barré, Julien Azuar, Franck Questel, Florence Vorspan, Vanessa Bloch, Frank Bellivier, Bernard Granger, Camille Barrault, Xavier Declèves
Baclofen has been proposed for few years to help treating alcohol-dependence at higher doses than those used in neurology. Baclofen pharmacokinetics has been previously well described at low oral or intravenous doses but remains poorly investigated with such high oral doses. We here describe dose regimens of baclofen in 143 alcohol-dependent-patients treated with steady-state oral doses of baclofen. Plasma baclofen levels were measured in blood samples using liquid chromatography coupled with tandem mass spectrometry...
November 1, 2017: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/29091313/exenatide-upregulates-gene-expression-of-glucagon-like-peptide-1-receptor-and-nerve-growth-factor-in-streptozotocin-nicotinamide-induced-diabetic-mice
#16
Esen Gumuslu, Naci Cine, Merve Ertan, Oguz Mutlu, Ipek Komsuoglu Celikyurt, Guner Ulak
Glucagon like peptide-1 (GLP-1) is an incretine hormon that has modulating effects on insulin release. GLP-1 and receptors for GLP-1 are widely expressed throughout the body including brain.The expression of GLP-1 receptors is very specific to large neurons in hippocampus, neocortex and cerebellum. GLP-1 receptor stimulation enhances glucose-dependent insulin secretion and lowers blood glucose in type 2 diabetes mellitus. Studies on adipobiology of neurotrophins have focused on nerve growth factor (NGF) as an example of adipose-derived neurotrophins...
November 1, 2017: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/29069531/factors-associated-with-the-variability-of-cni-blood-levels-in-kidney-recipients-grafted-for-more-than-1-year
#17
Stéphanie Belaiche, Bertrand Décaudin, Sébastien Dharancy, Sophie Gautier, Christian Noel, Pascal Odou, Marc Hazzan
The study of calcineurin inhibitor (CNI) blood level variability to evaluate adherence in transplantation has improved over the years. The aim of our study was to assess factors associated with this variability using the coefficient of variation (CV). A cross-sectional sample of kidney recipients grafted for more than 1 year was recruited. We recorded clinical data, data from a clinical pharmacist interview and from 6 questionnaires measuring adherence, satisfaction, behaviours, beliefs, perception of the illness and social vulnerability...
October 25, 2017: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/29059499/oligomeric-proanthocyanidins-protect-myocardium-by-mitigating-left-ventricular-remodeling-in-isoproterenol-induced-post-myocardial-infarction
#18
Ashokkumar Rathinavel, Jamuna Sankar, M S Sakeena Sadullah, Sivasithamparam Niranjali Devaraj
Extracellular matrix (ECM) remodeling is a major pathophysiological process during post myocardial infarction (MI). The activation, differentiation and proliferation of cardiac fibroblasts to myofibroblasts regulate the expression of ECM proteins. The signalling by Bone morphogenetic protein (BMP-4), an extra cellular ligand of the TGF-β family, has recently been identified as an essential pathway in regulating cardiovascular dysfunctions including myocardial fibrosis. Oligomeric proanthocyanidins (OPC) are well known for their cardioprotective activity...
October 23, 2017: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/29055166/drug-monitoring-of-sunitinib-in-patients-with-advanced-solid-tumors-a-monocentric-observational-french-study
#19
Luc Cabel, Benoit Blanchet, Audrey Thomas-Schoemann, Olivier Huillard, Audrey Bellesoeur, Anatole Cessot, Julie Giroux, Pascaline Boudou-Rouquette, Romain Coriat, Michel Vidal, Nathaniel E B Saidu, Lisa Golmard, Jérome Alexandre, Francois Goldwasser
Therapeutic drug monitoring (TDM) could be helpful in oral targeted therapies. Data are sparse to evaluate its impact on treatment management. This study aimed to determine a threshold value of plasma drug exposure associated with the occurrence of grade 3-4 toxicity, then the potential impact of TDM on clinical decision. Consecutive outpatients treated with sunitinib were prospectively monitored between days 21-28 of the first cycle, then monthly until disease progression. At each consultation, the composite AUCƬ,ss (sunitinib + active metabolite SU12662) was assayed...
October 21, 2017: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/29055145/positive-predictive-values-of-peripheral-arterial-and-venous-thrombosis-codes-in-french-hospital-database
#20
Mandy Prat, Hélène Derumeaux, Laurent Sailler, Maryse Lapeyre-Mestre, Guillaume Moulis
French hospital database, called Programme de Médicalisation des Systèmes d'Information (PMSI) covers all hospitals stays in France (>66 million inhabitants). The aim of this study was to estimate the positive predictive values (PPVs) of primary diagnosis codes of peripheral arterial and venous thrombosis codes in the PMSI, encoded with the International Classification of Diseases, 10(th) revision. Data were extracted from the PMSI database of Toulouse University Hospital, South of France. We identified all the hospital stays in 2015 with a code of peripheral arterial or venous thrombosis as primary diagnosis...
October 21, 2017: Fundamental & Clinical Pharmacology
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