Angiotensiini konverteeriva ensüümi inhibiitorid

Reniin-angiotensiin-aldosteroonsüsteem (RAAS) toimib sünergistlikult sümpaatilise närvisüsteemiga. Neerudest vabanev proteolüütiline ensüüm reniin on RAASi aktiveeriv aine, mille tulemusena tekib angiotensinogeenist angiotensiin I. Angiotensiini konverteeriv ensüüm (AKE) katalüüsib angiotensiin I konversiooni bioloogiliselt aktiivseks angiotensiin II kudedes ja plasmas. Angiotensiin II on vasokonstriktor ja stimuleerib neerupealsete koores aldosterooni sünteesi ja vabanemist. Aldosteroon etendab olulist osa neerude kaudu Na+ eritumise, kehavedeliku hulga ja veresoonte toonuse regulatsioonis. AKE inhibiitorid on tänapäeval leidnud kindla koha arteriaalse hüpertensiooni, kongestiivse ning müokardiinfarktijärgse südamepuudulikkuse ja diabeetilise nefropaatia ravis. Eesti Arst 2009; 88(6):443−44

Meditsiini õppekavad vajavad motiveeritud tudengeid

Eesti Arst 2022; 101(9):46

Farmakoloogia

Kursuse käigus tutvustatakse üliõpilastele farmakoloogia üldmõisteid ja ravimtoime printsiipe, räägitakse erinevatest ravimvormidest ja ravimite manustamise viisidest (vegetatiivsesse närvisüsteemi, südame-veresoonkonda ja hingamiselunditesse toimivad ravimid, põletikuvastased ravimid); antakse ülevaade illegaalsetest spordis kasutatavatest ainetest nagu ravimid ja mürgid ning nende tarbimisega kaasnevatest ohtudest inimorganismile (dopinguained, nais- ja meessuguhormoonid ja nende antagonistid, psühhotroopsed ained, ravimitoksikoloogia ja ravimiallergia). Kursus on kombineeritud auditoorne õpe veebipõhise toega. Üliõpilane osaleb aktiivselt loengutes ja seminarides täites talle antud ülesandeid ja suhtleb aktiivselt foorumis kaastudengite ning õppejõududega ette antud seminari teemadel.BeSt programmi toetusel loodud e-kursuse eessmärgiks on anda kehakultuuri teaduskonna füsioteraapia magistriõppe üliõpilastele baasteadmiseid ravimite ja mürkide toimest inimorganismile. Kursuse edukalt läbinud üliõpilased omavad teadmisi farmakoloogia üldmõistetest ja ravimtoime printsiipidest; omavad teavet erinevatest ravimvormidest ja ravimite manustamise viisidest; teavad olulisemaid ravimite gruppe ja ravimeid ning nende toimet inimorganismile, kes tegelevad aktiivselt spordiga; omavad teavet illegaalsetest spordis kasutatavatest dopinguainetest ning nende tarbimisega kaasnevatest ohtudest

Repeated Ethanol Exposure Alters DNA Methylation Status and Dynorphin/Kappa-Opioid Receptor Expression in Nucleus Accumbens of Alcohol-Preferring AA Rats

Growing evidence suggests that epigenetic mechanisms, such as DNA methylation and demethylation, and histone modifications, are involved in the development of alcohol and drug addiction. However, studies of alcohol use disorder (AUD) that are focused on epigenetic DNA modifications and gene expression changes remain conflicting. Our aim was to study the effect of repeated ethanol consumption on epigenetic regulatory enzymes such as DNA methyltransferase and demethylase enzymes and whether those changes affected dynorphin/kappa-opioid receptor system in the Nucleus Accumbens (NAc). Two groups of male alcohol-preferring Alko Alcohol (AA) rats, rats which are selectively bred for high voluntary alcohol consumption and one group of male Wistar rats were used. The first group of AA rats had access to alcohol (10% ethanol solution) for 90 min on Mondays, Wednesdays and Fridays over a period of 3 weeks to establish a stable baseline of ethanol intake (AA-ethanol). The second group of AA rats (AA-water) and the Wistar rats (Wistar-water) were provided with water. Using qPCR, we found that voluntary alcohol drinking increased Dnmt1, -3a, and -3b mRNA levels and did not affect Tet family transcripts in the AA-ethanol group when compared with AA- and Wistar-water rats. DNMT and TET enzymatic activity measurements showed similar results to qPCR, where DNMT activity was increased in AA-ethanol group compared with AA-water and Wistar-water groups, with no statistically significant difference between groups in TET enzyme activity. In line with previous data, we found an increased percentage of global DNA methylation and hydroxymethylation in the AA-ethanol group compared with control rats. Finally, we investigated changes of selected candidate genes from dynorphin/kappa-opioid receptor system (Pdyn, Kor) and Dnmt3a genes that might be important in AUD-related behaviour. Our gene expression and promoter methylation analysis revealed a significant increase in the mRNA levels of Pdyn, Kor, and Dnmt3a in the AA-ethanol group, however, these changes can only be partially associate with the aberrant DNA methylation in promoter areas of the selected candidate genes. Thus, our findings suggest that the aberrant DNA methylation is rather one of the several mechanisms involved in gene expression regulation in AA rat model.Peer reviewe

Key Learning Outcomes for Clinical Pharmacology and Therapeutics Education in Europe: A Modified Delphi Study.

Harmonizing clinical pharmacology and therapeutics (CPT) education in Europe is necessary to ensure that the prescribing competency of future doctors is of a uniform high standard. As there are currently no uniform requirements, our aim was to achieve consensus on key learning outcomes for undergraduate CPT education in Europe. We used a modified Delphi method consisting of three questionnaire rounds and a panel meeting. A total of 129 experts from 27 European countries were asked to rate 307 learning outcomes. In all, 92 experts (71%) completed all three questionnaire rounds, and 33 experts (26%) attended the meeting. 232 learning outcomes from the original list, 15 newly suggested and 5 rephrased outcomes were included. These 252 learning outcomes should be included in undergraduate CPT curricula to ensure that European graduates are able to prescribe safely and effectively. We provide a blueprint of a European core curriculum describing when and how the learning outcomes might be acquired

Opioidanalgeetikumid ja nende kasutamine Eestis

Valu on arsti poole pöördumise põhjusena üks sagedasemaid kaebusi ning üks tähtsamaid terapeutilist sekkumist nõudev sümptom. Valu võib olla nii iseseisev kui ka paljude haigustega kaasnev sümptom. Opioidide rühma kuuluvad ravimid on olulised keskmiste ja tugevate valude ravis, kuid võrreldes naaberriikidega on Eestis opioidanalgeetikumide kasutamine oluliselt väiksem. Artikli eesmärk on anda ülevaade valu mehhanismidest, opioidanalgeetikumidest ja nende tarvitamise statistikast viimase 10 aasta jooksul ning nende kasutamise vajadusest esmatasandi arstiabis

Enigmatic High Palaeolatitude Forests of Gondwanaland - a Case Study from the New Zealand Jurassic

Middle Jurassic fossil forest deposits from New Zealand, at a palaeolatitude of ~75-78 [degrees] South, provide evidence for a diverse vegetation association dominated by Filicopsida and Gymnospermopsida plants. Macrofloral and microfloral studies at present day Kawhia Harbour (North Island) and in the Curio Bay region (South Island) also recognise the preserved remains of Chlorophyta, Bryophyta and Lycopsida and interpret vegetation palaeo-profiles from the fossil flora assemblages. Fossil wood analysis identifies distinct, newly described taxa: Araucarioxylon sp. A, Araucarioxylon sp., Protocupressinoxylon sp. A, Podocarpoxylon sp. A and Protopodocarpoxylon sp.. Facies analysis implies vegetation growth in riverine depositional settings located on merged alluvial fan-toes along the Murihiku basin margin of the south-eastern Gondwanaland coast. Evidence from palaeosols and in-growth-position fossilised tree stumps suggest major floods inundated and destroyed successive forest generations at a minimum recurrence interval of at least 100-150 years. Interpretations from the distribution and structure of the in-growth-position fossilised tree stumps imply the growth of forests during the Middle Jurassic of varying, but generally high, densities with a distinct vertical structure of undergrowth, canopy and emergent layers. Analysis of fossil wood growth ring widths implies the trees grew rapidly when environmental conditions were favourable and that the forest productivity levels were comparable to those of modern tropical woodlands. Growth ring sequences studied imply dominantly uniform growing conditions, year to year, with variations possibly reflecting fluctuations in water supply. Rarely, variation in cell widths within individual growth rings suggests growth was disrupted during the first half of certain growing seasons, perhaps also due to changes in water supply or the occurrence of severe storms. Empirical solar radiation data from 75 [degrees] North applied to the Middle Jurassic palaeoenvironment and comparison with late-early Permian high palaeolatitude wood from Allan Hills in Antarctica suggests the trees were highly adapted to the near-polar light regime. Wood production was maximised even within the shaded canopy. Climatic parameters interpreted from the sediments and fossil flora suggest a near-tropical, but seasonal, palaeoclimate with wet and warm summers and arid, cool winters. These criteria compare well to simulated Jurassic Global Climate Models for the southeastern margin of Gondwanaland implying model reliability for the prediction of future global temperature trend

DNA Methylation Regulates Cocaine-Induced Behavioral Sensitization in Mice

The behavioral sensitization produced by repeated cocaine treatment represents the neural adaptations underlying some of the features of addiction in humans. Cocaine administrations induce neural adaptations through regulation of gene expression. Several studies suggest that epigenetic modifications, including DNA methylation, are the critical regulators of gene expression in the adult central nervous system. DNA methylation is catalyzed by DNA methyltransferases (DNMTs) and consequent promoter region hypermethylation is associated with transcriptional silencing. In this study a potential role for DNA methylation in a cocaine-induced behavioral sensitization model in mice was explored. We report that acute cocaine treatment caused an upregulation of DNMT3A and DNMT3B gene expression in the nucleus accumbens (NAc). Using methylated DNA immunoprecipitation, DNA bisulfite modification, and chromatin immunoprecipitation assays, we observed that cocaine treatment resulted in DNA hypermethylation and increased binding of methyl CpG binding protein 2 (MeCP2) at the protein phosphatase-1 catalytic subunit (PP1c) promoter. These changes are associated with transcriptional downregulation of PP1c in NAc. In contrast, acute and repeated cocaine administrations induced hypomethylation and decreased binding of MeCP2 at the fosB promoter, and these are associated with transcriptional upregulation of fosB in NAc. We also found that pharmacological inhibition of DNMT by zebularine treatment decreased cocaine-induced DNA hypermethylation at the PP1c promoter and attenuated PP1c mRNA downregulation in NAc. Finally, zebularine and cocaine co-treatment delayed the development of cocaine-induced behavioral sensitization. Together, these results suggest that dynamic changes of DNA methylation may be an important gene regulation mechanism underlying cocaine-induced behavioral sensitization