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Drug Metabolism and Personalized Therapy

Narendranath Vikkath, Prasanth Ariyannur, Krishnakumar N Menon, Bindhu Mr, Ashok Pillai
BACKGROUND: Central nervous system (CNS) hemangioblastoma (HB) is the most common tumor in the von Hippel Lindau (VHL) disorder, the hereditary tumor syndrome caused by the biallelic mutations of the VHL gene. The disrupted VHL and Elongin protein interaction on hypoxia-inducible factor-1α (HIF-1α) induces a set of hypoxia-inducible genes, resulting in an unchecked endothelial cell proliferation that then leads to hemangioblastoma formation. However, recent studies have shown that disruptive germline mutations of VHL need not result in hemangioblastoma, though it can cause other manifestations of the VHL syndrome...
May 29, 2018: Drug Metabolism and Personalized Therapy
Denis S Fedorinov, Karin B Mirzaev, Dmitriy V Ivashchenko, Ilyas I Temirbulatov, Dmitriy A Sychev, Nadezda R Maksimova, Jana V Chertovskih, Nyurguiana V Popova, Ksenia S Tayurskaya, Zoya A Rudykh
BACKGROUND: The focus of the study is to determine the prevalence of CYP2C19 alleles, associated with the risk of changes in the pharmacological response to clopidogrel and proton pump inhibitors in patients with acute coronary syndrome (ACS) and gastric ulcer from Russian and Yakut ethnic groups. METHODS: The research included 411 patients with ACS (143 Russians and 268 Yakuts) and 204 patients with histologically confirmed gastric ulcer (63 Russians and 141 Yakuts)...
June 27, 2018: Drug Metabolism and Personalized Therapy
Mahnaz Ahmadimanesh, Shahin Shadnia, Mohammad Reza Rouini, Behjat Sheikholeslami, Sara Ahsani Nasab, Mahmoud Ghazi-Khansari
BACKGROUND: Seizure is one of the important symptoms of tramadol poisoning, but its causes are still unknown. The aim of this study is to find a relationship between tramadol and the concentrations of its metabolites versus the incidence of seizures following the consumption of high doses of tramadol. METHODS: For this purpose, the blood samples of 120 tramadol-intoxicated patients were collected. The patients were divided in two groups (seizure and non-seizure)...
June 27, 2018: Drug Metabolism and Personalized Therapy
Dmitriy V Ivashchenko, Anastasia V Rudik, Andrey A Poloznikov, Sergey V Nikulin, Valeriy V Smirnov, Alexander G Tonevitsky, Eugeniy A Bryun, Dmitriy A Sychev
BACKGROUND: Phenazepam (bromdihydrochlorphenylbenzodiazepine) is the original Russian benzodiazepine tranquilizer belonging to 1,4-benzodiazepines. There is still limited knowledge about phenazepam's metabolic liver pathways and other pharmacokinetic features. METHODS: To determine phenazepam's metabolic pathways, the study was divided into three stages: in silico modeling, in vitro experiment (cell culture study), and in vivo confirmation. In silico modeling was performed on the specialized software PASS and GUSAR to evaluate phenazepam molecule affinity to different cytochromes...
June 27, 2018: Drug Metabolism and Personalized Therapy
Abdulsamet Erden, Emre Bilgin, Levent Kılıç, Alper Sarı, Berkan Armağan, Yahya Büyükaşık, Umut Kalyoncu
BACKGROUND: Relapsing polychondritis (RP) is a rare autoimmune disorder, and myelodysplastic syndrome (MDS) is accompanied by RP at variable rates. Herein, we report a case with RP and MDS who responded dramatically to 5-azacitidine for MDS. CASE PRESENTATION: With conventional immunosuppressive treatment, our patient had several episodes of different side effects, including infections. With the diagnosis of MDS and initiation of azacitidine treatment, all the manifestations of RP disappeared, and remission was achieved for MDS...
June 27, 2018: Drug Metabolism and Personalized Therapy
Sujit Nair, Adrián LLerena
No abstract text is available yet for this article.
June 27, 2018: Drug Metabolism and Personalized Therapy
Brendon Pearce, Zainonesa Abrahams-October, Lettilia Xhakaza, Clifford Jacobs, Mongi Benjeddou
BACKGROUND: Single nucleotide polymorphisms in promoter regions have been shown to alter the transcription of genes. Thus, SNPs in SLC22A2 can result in inter-individual variable response to medication. METHODS: The objective of the study was to investigate the effect of the African-specific promoter polymorphisms on the SLC22A2 gene expression levels in vitro. These included rs572296424 and rs150063153, which have been previously identified in the Xhosa population of South Africa...
June 27, 2018: Drug Metabolism and Personalized Therapy
Branko Srećković, Ivan Soldatovic, Emina Colak, Igor Mrdovic, Mirjana Sumarac-Dumanovic, Hristina Janeski, Nenad Janeski, Jasna Gacic, Vesna Dimitrijevic-Sreckovic
BACKGROUND: Abdominal adiposity has a central role in developing insulin resistance (IR) by releasing pro-inflammatory cytokines. Patients with metabolic syndrome (MS) have higher values of homocysteine. Hyperhomocysteinemia correlates with IR, increasing the oxidative stress. Oxidative stress causes endothelial dysfunction, hypertension and atherosclerosis. The objective of the study was to examine the correlation of homocysteine with siMS score and siMS risk score and with other MS co-founding factors...
June 27, 2018: Drug Metabolism and Personalized Therapy
Reenu Anne Joy, Narendranath Vikkath, Prasanth S Ariyannur
Hyaluronan is a ubiquitous high-molecular weight polymer of repeated disaccharides of glucuronic acid and N-acetylglucosamine. It is a membrane-bound, viscous material extruded into the extracellular matrix after being synthesized in the cytoplasm by hyaluronan synthases complex and a regulated degradation by a group of enzymes called hyaluronidases. Hyaluronan has varied biological roles on many vital organismal functions, such as cellular and tissue development, migration and repair after injury or inflammation and cancer genesis...
March 28, 2018: Drug Metabolism and Personalized Therapy
Swarup A V Shah, Minal U Paradkar, Devendra C Desai, Tester F Ashavaid
BACKGROUND: Thiopurine methyltransferase (TPMT) gene variants have achieved limited success in predicting the outcome of thiopurine therapy, which shows wide inter-individual variations. The literature indicates a strong association between the NUDT15 gene variant and thiopurine-induced toxicity in Asian patients. The present study intends to explore the role of the NUDT15 variant (C415T) in Indian patients on thiopurine therapy. METHODS: NUDT15 and TPMT genotyping were performed using amplification-refractory mutation system-polymerase chain reaction (ARMS-PCR) and the restriction fragment length polymorphism (RFLP) technique...
March 28, 2018: Drug Metabolism and Personalized Therapy
Henrik Berg Rasmussen, Majbritt Busk Madsen
The carboxylesterase 1 gene (CES1) encodes a hydrolase that metabolizes commonly used drugs. The CES1-related pseudogene, carboxylesterase 1 pseudogene 1 (CES1P1), has been implicated in gene exchange with CES1 and in the formation of hybrid genes including the carboxylesterase 1A2 gene (CES1A2). Hence, the CES1 region is complex. Using in silico PCR and alignment, we assessed the specificity of PCR-assisted procedures for genotyping CES1, CES1A2 and CES1P1 in studies identified in PubMed. We identified 33 such studies and excluded those that were not the first to use a procedure or lacked sequence information...
March 28, 2018: Drug Metabolism and Personalized Therapy
Baraa Alghalyini, Said El Shamieh, Ali Salami, Sophie Visvikis Siest, Hana M Fakhoury, Rajaa Fakhoury
Background Statin therapy used to lower cholesterol levels results in a substantial reduction in cardiovascular complications. Previous observations in different ethnic populations showed that rs2306283A>G, p.Asn130Asp and rs4149056T>C, p.Val174Ala in solute carrier organic anion transporter 1B1 (SLCO1B1) gene encoding the organic transporter protein may be responsible for statin uptake, thus explaining the majority of statin-associated symptoms. In addition to the genetic component, vitamin D (vit D) deficiency is common in Saudi Arabia and worldwide and may cause muscle dysfunction and ache...
March 28, 2018: Drug Metabolism and Personalized Therapy
Kirsten M Pondman, Ron H N van Schaik, Jan van der Weide
BACKGROUND: CYP2D6 is responsible for the metabolism of approximately 25% of all drugs. The expression of cytochrome P450 2D6 (CYP2D6) is influenced by a combination of factors including polymorphisms in the CYP2D6 gene. Analysis of the CYP2D6 genotype is used to personalize the medication to a patient's metabolism. Although many genotypes can be determined using standard genotype analysis, in some cases, an incomplete analysis is performed. The CYP2D6 genotype *1/*4 often occurs in combination with a multiplication of the CYP2D6 gene, and is reported as (*1/*4)xN...
March 28, 2018: Drug Metabolism and Personalized Therapy
Dagmar F Hernandez-Suarez, Hector Núñez-Medina, Stuart A Scott, Angel Lopez-Candales, Jose M Wiley, Mario J Garcia, Kyle Melin, Karid Nieves-Borrero, Christina Rodriguez-Ruiz, Lorraine Marshall, Jorge Duconge
BACKGROUND: Antiplatelet therapy with clopidogrel is recommended to reduce cardiovascular events in patients with peripheral artery disease (PAD); however, clopidogrel efficacy has not been adequately studied in this patient population. Therefore, we aimed to determine the effects of cilostazol therapy on platelet reactivity among PAD patients on clopidogrel. METHODS: We performed a cross-sectional pilot study of 46 Puerto Rican patients diagnosed with PAD. The cohort was divided based on use of clopidogrel and cilostazol (n=24) or clopidogrel alone (n=22)...
March 28, 2018: Drug Metabolism and Personalized Therapy
Ana M Peiró, César Margargit, Adrián LLerena
No abstract text is available yet for this article.
March 28, 2018: Drug Metabolism and Personalized Therapy
Ursula Amstutz, Vid Mlakar, Patricia Huezo-Diaz Curtis, Caroline Samer, Pierre Baumann, Roland P Bühlmann, Peter Meier-Abt, Urs A Meyer, Ron H N van Schaik, Marc Ansari
No abstract text is available yet for this article.
December 20, 2017: Drug Metabolism and Personalized Therapy
Heike Jahnke
No abstract text is available yet for this article.
December 20, 2017: Drug Metabolism and Personalized Therapy
Carlos A Castro-Rojas, Antonio R Esparza-Mota, Francisco Hernandez-Cabrera, Viktor J Romero-Diaz, Juan F Gonzalez-Guerrero, Hector Maldonado-Garza, Irma S Garcia-Gonzalez, Sergio Buenaventura-Cisneros, Josefina Y Sanchez-Lopez, Rocio Ortiz-Lopez, Alberto Camacho-Morales, Oralia Barboza-Quintana, Augusto Rojas-Martinez
BACKGROUND: Fluoropyrimidines form the chemotherapy backbone of advanced and metastatic colorectal cancer (CRC). These drugs are frequently associated with toxicity events that result in dose adjustments and even suspension of the treatment. The thymidylate synthase (TYMS) gene is a potential marker of response and toxicity to fluoropyirimidines as this enzyme is the molecular target of these drugs. Our aim was to assess the association between variants of TYMS with response and toxicity to fluoropyrimidines in patients with CRC in independent retrospective and prospective studies...
December 20, 2017: Drug Metabolism and Personalized Therapy
Jaroslav A Hubacek, Vera Adamkova, Lukas Zlatohlavek, Lenka Steiner-Mrazova, Michal Vrablik
BACKGROUND: The gene COQ2, encoding 4-hydroxybenzoate-polyprenyltransferase (coenzyme Q2), belongs to the candidates potentially influencing statin treatment tolerability. This enzyme is involved in the biosynthesis of coenzyme Q10 (CoQ10), in which depletion induced by statin treatment is implicated in the development of statin-associated muscle symptoms (SAMS). Thus, polymorphisms in the COQ2 gene might explain susceptibility to SAMS. METHODS: Adult patients with SAMS (on low doses of atorvastatin and simvastatin)-induced myalgia/myopathy (n=278), patients on statins but without SAMS (n=293) and population (part of the post-MONICA [Multinational MONItoring of trends and determinants in CArdiovascular disease] study) controls (n=561) were genotyped (polymerase chain reaction-restriction fragment length polymorphism [PCR-RFLP] assay) for rs6535454 and rs4693075 polymorphisms within the COQ2 gene loci...
December 20, 2017: Drug Metabolism and Personalized Therapy
Georgia Ragia, Ioanna-Maria Karantza, Eleni Kelli-Kota, Vana Kolovou, Genovefa Kolovou, Stavros Konstantinides, Efstratios Maltezos, Anna Tavridou, Dimitrios Tziakas, Anke H Maitland-van der Zee, Vangelis G Manolopoulos
BACKGROUND: We have earlier developed a pharmacogenomic algorithm for acenocoumarol dose prediction in Greek patients that included CYP2C9/VKORC1 genetic information. This study aims at analyzing the potential effect of CYP4F2, CYP2C19, and CYP1A2 gene polymorphisms on acenocoumarol dose requirements and at further improving the Greek-specific pharmacogenomic algorithm. METHODS: A total of 205 Greek patients taking acenocoumarol (140 who reached and 65 who did not reach stable dose), participants of acenocoumarol EU-PACT trial, were included in the study...
December 20, 2017: Drug Metabolism and Personalized Therapy
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