Single nucleotide polymorphisms in the intergenic region between metformin transporter OCT2 and OCT3 coding genes are associated with short-Term response to metformin monotherapy in type 2 diabetes mellitus patients

Publisher Copyright: © 2016 The authors Published by Bioscientifica Ltd. Copyright: Copyright 2017 Elsevier B.V., All rights reserved.Objective(s): High variability in clinical response to metformin is often observed in type 2 diabetes (T2D) patients, and it highlights the need for identification of genetic components affecting the efficiency of metformin therapy. Aim of this observational study is to evaluate the role of tagSNPs (tagging single nucleotide polymorphisms) from genomic regions coding for six metformin transporter genes with respect to the short-Term efficiency. Design: 102 tagSNPs in 6 genes coding for metformin transporters were genotyped in the group of 102 T2D patients treated with metformin for 3 months. Methods: Most significant hits were analyzed in the group of 131 T2D patients from Slovakia. Pharmacokinetic study in 25 healthy nondiabetic volunteers was conducted to investigate the effects of identified polymorphisms. Results: In the discovery group of 102 patients, minor alleles of rs3119309, rs7757336 and rs2481030 were significantly nominally associated with metformin inefficiency (P = 1.9 × 106 to 8.1 × 106). Effects of rs2481030 and rs7757336 did not replicate in the group of 131 T2DM patients from Slovakia alone, whereas rs7757336 was significantly associated with a reduced metformin response in combined group. In pharmacokinetic study, group of individuals harboring risk alleles of rs7757336 and rs2481030 displayed significantly reduced AUC∞ of metformin in plasma. Conclusions: For the first time, we have identified an association between the lack of metformin response and SNPs rs3119309 and rs7757336 located in the 5 flanking region of the genes coding for Organic cation transporter 2 and rs2481030 located in the 5 flanking region of Organic cation transporter 3 that was supported by the results of a pharmacokinetic study on 25 healthy volunteers.publishersversionPeer reviewe

Quantitative determination of metformin in biological samples by liquid chromatography-mass spectrometry

Metformīna noteikšana bioloģiskajos paraugos ar šķidrumu hromatogrāfijas-masspektrometrijas metodi. Hartmane. D., zinātniskie vadītāji: Dr. chem. Grīnberga S., asoc. prof., Dr. chem. Mekšs P. Maģistra darbs, 61 lappuse, 25 attēli, 5 tabulas, 46 literatūras avoti, 2 pielikumi. Latviešu valodā. Darbā ir apkopota literatūra par matricas efekta ietekmi, bioloģisko paraugu sagatavošanu un metformīna kvantitatīvo noteikšanu ar šķidrumu hromatogrāfijas metodēm. Izstrādāta hromatogrāfijas-tandēmmasspektrometrijas metode kvantitatīvai metformīna noteikšanai cilvēku bioloģiskajos paraugos. Metode validēta metformīna noteikšanai plazmas un eritrocītu paraugos. Metode pielietota metformīna satura noteikšanai cilvēka asins plazmā, eritrocītos un urīnā. METFORMĪNS, HILIC, ŠĶIDRUMU HROMATOGRĀFIJA, TANDĒMA MASSPEKTROMETRIJA, MATRICAS EFEKTS.Quantitative determination of metformin in biological samples by liquid chromatography-mass spectrometry. Hartmane D., supervisors: Dr. chem. Grīnberga S., asoc. prof., Dr. chem. Mekšs P. Master thesis, 61 page, 25 figures, 5 tables, 46 literature references, 2 appendices. In Latvian. The theoretical part of this thesis contains a literature review of matrix effect, biological sample preparation and methods for quantitative analysis of metformin by liquid chromatography. Liquid chromatography-tandem mass spectrometry method was developed for quantitative determination of metformin in human biological samples. Method was validated for metformin determination in plasma and erythrocyte samples. Method was used for quantitative metformin determination in human blood plasma, erythrocytes and urine. METFORMIN, HILIC, LIQUID CHROMATOGRAPHY, TANDEM MASS SPECTROMETRY, MATRIX EFFECT

l-Carnitine Supplementation in Older Women. A Pilot Study on Aging Skeletal Muscle Mass and Function

Skeletal muscle wasting, associated with aging, may be regulated by the inflammatory cytokines as well as by insulin-like growth factor 1 (IGF-1). l-carnitine possesses anti-inflammatory properties and increases plasma IGF-1 concentration, leading to the regulation of the genes responsible for protein catabolism and anabolism. The purpose of the present study was to evaluate the effect of a 24-week l-carnitine supplementation on serum inflammatory markers, IGF-1, body composition and skeletal muscle strength in healthy human subjects over 65 years of age. Women between 65 and 70 years of age were supplemented for 24 weeks with either 1500 mg l-carnitine-l-tartrate or an isonitrogenous placebo per day in a double-blind fashion. Before and after the supplementation protocol, body mass and composition, as well as knee extensor and flexor muscle strength were determined. In the blood samples, free carnitine, interleukin-6, tumor necrosis factor-α, C-reactive protein and IGF-1 were determined. A marked increase in free plasma carnitine concentration was observed due to l-carnitine supplementation. No substantial changes in other parameters were noted. In the current study, supplementation for 24 weeks affected neither the skeletal muscle strength nor circulating markers in healthy women over 65 years of age. Positive and negative aspects of l-carnitine supplementation need to be clarified

Mākslu terapija dažādām klientu / pacientu grupām

Šis rakstu krājums ir izveidots un publicēts Erasmus Mūžizglītības intensīvās programmas projektā “Mākslu terapija dažādām klientu / pacientu grupām” (2014) Rīgas Stradiņa universitātes Rehabilitācijas fakultātē, profesionālā maģistra studiju programmā “Mākslas terapija” sadarbībā ar projekta partneriem. Raksti ir balstīti uz teorētisko prezentāciju un autoru semināru saturu intensīvās programmas laikā. Rakstu krājumā aprakstīts teorētiskais un praktiskais darbs ar veselības aprūpes disciplīnu - mākslas terapijas specializācijām - mākslas terapijas, deju kustību terapijas, mūzikas terapijas iespējas ar dažādām klientu / pacientu grupām veselības aprūpē, sociālajā aprūpē un izglītības vidē. Rakstu krājumā ir dažādi mākslas terapeiti no Igaunijas, Latvijas, Lietuvas, Vācijas un Lielbritānijas, kā arī viņu praktiskās pieredzes kopsavilkums. Gadījumu izpēte ir neseno pētījumu rezultāti mākslas terapijas jomā. Raksti akcentē un raksturo mākslas terapijas specializācijas specifiku un piedāvā iespējas darbā ar dažādām klientu / pacientu grupām. Kolekcijā tiek piedāvāti daudzdimensionāli skati uz mākslas terapijas praktisko daļu. Tas arī demonstrē dažādus terapeitiskos ietvarus, medicīnisko, psiholoģisko teoriju integrāciju, kas tiek izmantota mākslas terapijas pielietojamības pamatā, piedāvā dažus uz mākslu balstīta novērtējuma aspektus un dalās noderīgā pieredzē. Autori piedāvā mūsdienu pieejas mākslas terapijas darbos. Projekta galvenie mērķi bija nodrošināt pieredzes apmaiņu, izmantojot aktivitātes starp projekta partneriem; iegūt un attīstīt jaunas zināšanas un prasmes; izveidot norādes materiālus mākslas terapijas darbiem dažādām klientu / pacientu grupām; un veicināt turpmāku mākslas terapijas attīstību projektā iesaistītajās valstīs