Microcystins (MCs) are a group of closely related toxic cyclic heptapeptides produced by common cyanobacteria (blue±green algae). Their toxicity is associated with speci®c inhibition of intracellular protein phosphatases type-1 and type-2A (PP1 and PP2A, respectively). We have developed a battery of antibodies to microcystins using chemical modi®cation (aminoethylation) of one of its core amino acids, N-methyl-dehydroalanine. The developed antibodies displayed dierent reactivities to closely related MCs. Selected monoclonal antibodies were used for quantitative competitive ELISA assays. The analytical sensitivity of these assays was up to 1 ng/ml. Comparison of the developed ELISA tests with HPLC-based measurements of MCs in laboratory and ®eld samples showed a good correspondence between the results yielded by these two methods. The antibodies developed by this technique provide the means for developing extremely sensitive and speci®c analytical assays for direct measurement of toxins in cyanobacterial or water samples. 7
 îáçîðå îòðàaeåíû îñíîâíûå íàïðàâëåíèè ôàðìàêîãåíåòè÷åñêèõ èññëåäîâàíèé ïðèìå-íåíèÿ ìåòôîðìèíà ó áîëüíûõ ñàõàðíûì äèàáåòîì 2 òèïà. Ïðèâåäåíû ðåçóëüòàòû èçó÷åíèÿ ïîëèìîðôèçìîâ ãåíîâ áåëêîâ, ó÷àñòâóþùèõ â ôàðìàêîêèíåòèêå ïðåïàðàòà, à òàêaeå ñäåëà-íû ïðåäïîëîaeåíèÿ îòíîñèòåëüíî äðóãèõ ãåíîâ, êîòîðûå ìîãóò îáóñëàâëèâàòü îñîáåííîñòè ôàðìàêîäèíàìèêè ïðåïàðàòà.Êëþ÷åâûå ñëîâà: ôàðìàêîãåíåòèêà; ïåðñîíèôèêàöèÿ; ìåòôîðìèí; ôàðìàêîêèíåòèêà; ôàðìàêîäèíàìèêà.Àêòèâíîå èññëåäîâàíèå ãåíîòèïà â ñâÿçè ñ âîçìîaeíî-ñòüþ ïðîãíîçèðîâàíèÿ äåéñòâèÿ îïðåäåë¸ííûõ ïðåïàðà-òîâ íàñ÷èòûâàåò îêîëî 10 ëåò.  ïîñëåäíåå âðåìÿ ïðåä-ïðèíÿòû îïðåäåëåííûå óñèëèÿ â ýòîì íàïðàâëåíèè è íà-ðÿäó ñ èçâåñòíûìè ãåíîòèïàìè âûÿâëÿþòñÿ íîâûå ãå-íû-êàíäèäàòû, ìîäèôèêàöèè êîòîðûõ ìîaeíî ñâÿçàòü ñ ýôôåêòèâíîñòüþ èëè íåóäà÷åé ïðè èñïîëüçîâàíèè òåõ èëè èíûõ ïðåïàðàòîâ.Ïðåïàðàòîì âûáîðà äëÿ èíèöèàöèè òåðàïèè áîëüíûõ ñàõàðíûì äèàáåòîì 2 òèïà (ÑÄ2) ñ÷èòàþò ìåòôîðìèí. Îñíîâíûì ìåõàíèçìîì äåéñòâèÿ (ïðåïàðàò èç ãðóïïû áè-ãóàíèäîâ, ïîâûøàþùèé ïå÷åíî÷íóþ è ïåðèôåðè÷åñêóþ ÷óâñòâèòåëüíîñòü ê ýíäîãåííîìó èíñóëèíó, íå âëèÿÿ íà åãî ñåêðåöèþ) ÿâëÿåòñÿ ñíèaeåíèå ïðîäóêöèè ãëþêîçû ïå-÷åíüþ, ïîâûøåíèå çàõâàòà ãëþêîçû ìûøöàìè è aeèðîâîé òêàíüþ ïóòåì óñèëåíèÿ ñâÿçûâàíèÿ èíñóëèíà ñ ðåöåïòî-ðàìè è ïîâûøåíèÿ àêòèâíîñòè òðàíñïîðòåðîâ ãëþêîçû ÃËÞÒ-1 è ÃËÞÒ-4. Ñíèaeåíèå óðîâíÿ ãëèêèðîâàííîãî ãåìîãëîáèíà â ðåçóëüòàòå ïðèìåíåíèÿ ìåòôîðìèíà íà-áëþäàåòñÿ â ïðåäåëàõ 1 -2 % [1, 3].22 íîÿáðÿ 2010 ã. â aeóðíàëå "The Year in Diabetes and Obesity" áûëà îïóáëèêîâàíà ñòàòüÿ Liana K. Billings è Jose C. Florez "The genetics of type 2 diabetes: what have we learned from GWAS?", â êîòîðîé áûëà îáîáùåíà èí-ôîðìàöèÿ î ãåíàõ, ðàçëè÷íûì îáðàçîì ñâÿçàííûõ ñ ðàç-âèòèåì ÑÄ2 [12]. Ê 2011 ã. ïîÿâèëàñü ñâîäíàÿ èíôîðìàöèÿ î âîçìîaeíûõ ãåíàõ-êàíäèäàòàõ, îòâåòñòâåííûõ çà ýôôåêòèâíîñòü ïå-ðîðàëüíûõ ñàõàðîñíèaeàþùèõ ïðåïàðàòîâ (ÏÑÑÏ), â ÷à-ñòíîñòè, ìåòôîðìèíà (ðèñ. 1).  îáøèðíîì èññëåäîâàíèè GoDARTS (5 386 ïàöèåíòîâ ñ ÑÄ2) ñ ïîìîùüþ GCTA ìå-òîäà (êàðòèðîâàíèå ãåíîâ) áûëî âûÿâëåíî, ÷òî îñîáåííî-ñòè ôàðìàêîëîãè÷åñêîãî îòâåòà íà ìåòôîðìèí ÿâëÿþòñÿ íàñëåäñòâåííûì ïðèçíàêîì è ìîãóò âàðüèðîâàòü â çàâè-ñèìîñòè îò ãåíîòèïà ëîêóñà ãåíà àòàêñèè-òåëåàíãèýêòà-çèè (ÀÒÌ) [58]. íàñòîÿùåå âðåìÿ âñ¸áîëüøèé èíòåðåñ âûçûâàþò ïîëèìîðôèçì ãåíîâ, ó÷àñòâóþùèõ êàê â ôàðìàêîêèíåòè-êå, òàê è â ôàðìàêîäèíàìèêå ïåðîðàëüíûõ ñàõàðîñíè-aeàþùèõ ïðåïàðàòîâ [21]. Îäíàêî ìíîãèå èññëåäîâàòåëè îòìå÷àþò âûñîêóþ âåðîÿòíîñòü âëèÿíèÿ è äðóãèõ ãåíîâ, òàêèõ, êàê, íàïðèìåð, ôàêòîð òðàíñêðèïöèè ãåïàòîöèòîâ 4-a [24].  ñâÿçè ñ ýòèì ïîèñê íîâûõ ðåãóëÿòîðíûõ è äðóãèõ ãåíîâ-ìèøåíåé è èõ ïîëèìîðôèçìà, îòâå÷àþùèõ çà ýôôåêòèâíîñòü ÏÑÑÏ, îñòà¸òñÿ àêòóàëüíîé ïðîáëå-ìîé.Îñîáûé èíòåðåñ, êàê âèäíî èç äèàãðàììû, ïðåäñòàâ-ëÿåò ôàðìàêîãåíåòè÷åñêîå èññëåäîâàíèå ïðèìåíåíèÿ ìåòôîðìèíà èç-çà òîãî, ÷òî äàííûé ïðåïàðàò èñïîëüçóåò-ñÿ â ìåäèöèíñêîé ïðàêòèêå áîëåå ïîëóâåêà è ÿâëÿåòñÿ ïåðâûì ýòàïîì ìåäèêàìåíòîçíîé òåðàïèè ÑÄ2. Ýôôåêò ìåòôîðìèíà çàâèñèò îò âñàñûâàíèÿ, òðàíñïîðòèðîâêè, ðàñïðåäåëåíèÿ è âûâåäåíèÿ âåùåñòâà. Ïðè ýòîì ñóùåñò-âóþò ðàçíî÷òåíèÿ ïî ïîâîäó âëèÿíèÿ ïîëèìîðôèçìà òðàí...
Локальные повреждения тканей, возникающие нередко в местах инъекций качественных лекарств, могут являться следствием нарушения медицинским персоналом правил асептики и антисептики или наличием у лекарств агрессивной физико-химической активности. Местное раздражающее действие у растворов для инъекций может быть вызвано наличием в их составе ингредиентов, обладающих прижигающим действием, либо их высокой концентрацией, которая придает раствору чрезмерно высокую гиперосмотическую активность. Проведены исследования динамики состояния кожи и подкожно-жировой клетчатки у поросят в местах подкожных инъекций растворов нестероидных противовоспалительных средств (НПВС) (метамизол натрия, кетопрофен, кеторолак, диклофенак). Результаты экспериментов показали, что качественные растворы указанных НПВС могут оказывать местное раздражающее действие на подкожно-жировую клетчатку без нарушения правил асептики и антисептики. Показано, что причиной местного раздражающего действия препаратов может быть их высокая осмотическая активность и/или наличие в их составе таких ингредиентов, как пропиленгликоль и бензиловый спирт, которые обладают прижигающим действием. Для профилактики постинъекционных некрозов рекомендуется перед инъекцией разводить растворы указанных средств водой для инъекции до уровня изотонической активности.
The aim of the research was to study the potential response to pharmacotherapy in patients with type 2 diabetes mellitus considering the single nucleotide polymorphisms in the genes encoding for endothelial nitric oxide synthase, 8-oxoguanine DNA glycosylase, and p53 protein as well as their combinations.Materials and Methods. A total of 89 patients with newly diagnosed type 2 diabetes mellitus before the start of pharmacotherapy and 80 diabetes-free individuals were examined. Single nucleotide polymorphisms of endothelial nitric oxide synthase, 8-oxoguanine DNA glycosylase, and p53 protein, as well as their combinations of polymorphic genes, were tested.Results. The occurrence rate of the above polymorphic genes in patients with newly diagnosed type 2 diabetes mellitus is close to that in non-diabetic subjects. The most common gene combinations in patients with type 2 diabetes mellitus and the respective controls have been identified. The polygenomic nature of type 2 diabetes mellitus necessitates considering all possible combinations of polymorphic genes. Conclusion.The results substantiate the need to identify combinations of polymorphisms in patients with newly diagnosed type 2 diabetes mellitus in order to personalize drug therapy and increase its efficacy.
This review analyzes the research results of additional effects and mechanisms of action of sugar-reducing drugs. Hence it has been suggested that asymmetric dimethylarginine may be a target molecule for metformin, vildagliptin, and combinations thereof. (For citation: Urakov AL, Gurevich KG, Sorokina IA, et al. Metformin and vildagliptin combination: a new approach of endothelial nitric oxide synthase activity regulation and metabolism in diabetes mellitus type 2. Reviews on Clinical Pharmacology and Drug Therapy. 2018;16(2):5-12. doi: 10.17816/RCF1625-12).
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