RNA interferencija kao novi terapijski postupak

The basic principle of RNA interference, a possible new therapeutic tool, involves destruction of messenger RNA upon interaction with homologous double-stranded RNA present in the cell cytoplasm. Studies have shown that both viral and non-viral small interfering RNA delivery methods and delivery of chemically synthesized small interfering RNAs to the cell can provide selective gene suppression through this mechanism, both in vitro and in vivo. Before becoming a functional therapeutic tool, there are a number of problems concerning RNA interference that should be solved. Major problems involve off-target effects, insertional mutagenesis and malignant transformation, as well as problems of delivery methods and reduction of toxicity.Osnovni je princip RNA interferencije razgradnja glasničke RNA nakon interakcije s dvolančanom interferirajućom RNA u citoplazmi stanice. Istraživanja su pokazala da unos malih interferirajućih RNA pomoću virusa ili uklapanjem u kemijski sintetizirane komplekse u stanici može selektivno spriječiti ekspresiju gena u pokusima in vitro i in vivo. Da bi se RNA interferencija mogla primijeniti kao terapijski postupak, moraju se još razriješiti mnogi problemi. Neki od većih problema su djelovanje malih interferirajućih RNA izvan ciljanoga gena, mutageneza koja može nastati zbog nasumične ugradnje, maligni učinak, te problemi zbog njihova unosa i smanjivanja toksičnosti u stanicama

Poslijediplomska sveučilišna naobrazba u području medicinske biokemije na Farmaceutsko‑bio kemijskom fakultetu Sveučilišta u Zagrebu

U radu je prikazan razvoj i unapređenje doktorske naobrazbe na Farmaceutsko-biokemijskom fakultetu Sveučilišta u Zagrebu. Farmaceutsko-biokemijski fakultet započeo je znanstvenu poslijediplomsku edukaciju 1961. pokretanjem i izvođenjem triju znanstvenih magistarskih studijskih programa. Tijekom skoro šest desetljeća poslijediplomska naobrazba doživljavala je brojne promjene, od ukidanja magistarskih studija do uvođenja trogodišnjih doktorskih studija u skladu s Bolonjskim procesom. Farmaceutsko-biokemijski fakultet Sveučilišta u Zagrebu od 2006. izvodi jedan poslijediplomski sveučilišni studijski program Farmaceutsko-biokemijske znanosti koji je ocijenjen ocjenom visoke kvalitete u reakreditaciji provedenoj u ak. god. 2016./2017. U radu je navedena struktura doktorskoga studijskoga programa, upisna politika, ishodi studijskoga programa te dodatne aktivnosti Farmaceutsko-biokemijskoga fakulteta koje osiguravaju visoku kvalitetu navedenoga doktorskoga studija

Poslijediplomska sveučilišna naobrazba u području medicinske biokemije na Farmaceutsko‑bio kemijskom fakultetu Sveučilišta u Zagrebu

U radu je prikazan razvoj i unapređenje doktorske naobrazbe na Farmaceutsko-biokemijskom fakultetu Sveučilišta u Zagrebu. Farmaceutsko-biokemijski fakultet započeo je znanstvenu poslijediplomsku edukaciju 1961. pokretanjem i izvođenjem triju znanstvenih magistarskih studijskih programa. Tijekom skoro šest desetljeća poslijediplomska naobrazba doživljavala je brojne promjene, od ukidanja magistarskih studija do uvođenja trogodišnjih doktorskih studija u skladu s Bolonjskim procesom. Farmaceutsko-biokemijski fakultet Sveučilišta u Zagrebu od 2006. izvodi jedan poslijediplomski sveučilišni studijski program Farmaceutsko-biokemijske znanosti koji je ocijenjen ocjenom visoke kvalitete u reakreditaciji provedenoj u ak. god. 2016./2017. U radu je navedena struktura doktorskoga studijskoga programa, upisna politika, ishodi studijskoga programa te dodatne aktivnosti Farmaceutsko-biokemijskoga fakulteta koje osiguravaju visoku kvalitetu navedenoga doktorskoga studija

Frequency of galactose-1-phosphate uridyl transferase gene mutations in healthy population of Croatia

Galactosemia is a human disease caused by deficient activity of each one of the three enzymes involved in galactose metabolism, galactokinase (GALK), galactose-1-phosphate uridyl transferase (GALT) and UDP-galactose-4-epimerase (GALE). Absence or deficiency of GALT activity results in classical galactosemia. This disorder exhibits allelic heterogeneity in different populations and ethnic groups. The aim of this study was to search for galactosemia mutations Q188R, N314D, and K285N in healthy population of Croatia. DNA samples from 221 subjects were analyzed by the polymerase chain reaction, followed by digestion with restriction endonucleases (PCR-RFLP procedure). Allele frequencies for Q188R, N314D, and K285N were found to be 0.2 %, 7.5 % and 0 %, respectively, and correlate well with those published for most other healthy Caucasian populations

RNA interferencija kao novi terapijski postupak

The basic principle of RNA interference, a possible new therapeutic tool, involves destruction of messenger RNA upon interaction with homologous double-stranded RNA present in the cell cytoplasm. Studies have shown that both viral and non-viral small interfering RNA delivery methods and delivery of chemically synthesized small interfering RNAs to the cell can provide selective gene suppression through this mechanism, both in vitro and in vivo. Before becoming a functional therapeutic tool, there are a number of problems concerning RNA interference that should be solved. Major problems involve off-target effects, insertional mutagenesis and malignant transformation, as well as problems of delivery methods and reduction of toxicity.Osnovni je princip RNA interferencije razgradnja glasničke RNA nakon interakcije s dvolančanom interferirajućom RNA u citoplazmi stanice. Istraživanja su pokazala da unos malih interferirajućih RNA pomoću virusa ili uklapanjem u kemijski sintetizirane komplekse u stanici može selektivno spriječiti ekspresiju gena u pokusima in vitro i in vivo. Da bi se RNA interferencija mogla primijeniti kao terapijski postupak, moraju se još razriješiti mnogi problemi. Neki od većih problema su djelovanje malih interferirajućih RNA izvan ciljanoga gena, mutageneza koja može nastati zbog nasumične ugradnje, maligni učinak, te problemi zbog njihova unosa i smanjivanja toksičnosti u stanicama

A novel approach for more precise quantification of M-protein using variables derived from immunosubtraction electropherogram and associated biochemistry analytes

IntroductionDue to limitations in currently used methodologies, the widely acknowledged approach for quantifying M-protein (MP) is not available. If employed as a source of quantitative data, the immunosubtraction electropherogram (IS-EPG), a qualitative analysis of MP, has the potential to overcome known analytical issues. The aim of this study is to explore measured and derived variables obtained from immunosubtraction electropherogram as a tool for quantifying MP and to compare the derived results to currently available methods. Materials and methodsMeasurands were amplitudes of MP and albumin fractions. Assessed derived variables included also immunoglobulin (Ig) G, IgA, IgM and total protein data. Capillary electrophoresis was used for determination of MP (in % of total protein concentration, or concentration of MP in g/L) by perpendicular drop and tangent skimming method. ResultsPassing-Bablok analysis showed the most comparable results in D1Ig and D1nIg variables, and the largest discrepancies in AD1nIg and AD2nIg variables. The background presence had greater impact on D1nIg comparison results than did on D1Ig results. The contribution of albumin fraction data did not improve the comparability of the results. The coefficients of variation of derived variables were lower (maximum 3.1%) than those obtained by densitometric measurements, regardless of MP concentration, polyclonal background, or migration pattern (2.3-37.7%). ConclusionThe amplitude of MP spike in IS-EPG is an valuable measurand to compute derived variables for quantifying MP. The most comparable results were achieved with the D1Ig variable. Patients with monoclonal gammopathy can benefit from increased precision employing an objective and background independent measurand, especially during longitudinal follow-up

Frequency of Galactose-1-phosphate Uridyl Transferase Gene Mutations in Healthy Population of Croatia

Galactosemia is a human disease caused by deficient activity of each one of the three enzymes involved in galactose metabolism, galactokinase (GALK), galactose-1-phosphate uridyl transferase (GALT) and UDP-galactose-4-epimerase (GALE). Absence or deficiency of GALT activity results in classical galactosemia. This disorder exhibits allelic heterogeneity in different populations and ethnic groups. The aim of this study was to search for galactosemia mutations Q188R, N314D, and K285N in healthy population of Croatia. DNA samples from 221 subjects were analyzed by the polymerase chain reaction, followed by digestion with restriction endonucleases (PCR-RFLP procedure). Allele frequencies for Q188R, N314D, and K285N were found to be 0.2 %, 7.5 % and 0 %, respectively, and correlate well with those published for most other healthy Caucasian populations

Utjecaj različitih koncentracija peroksovanadijevog spoja bpV(phen) na preživljavanje PC12 stanica

Peroxovanadium compounds are potent insulinomimetic agents and protein tyrosine phosphatase inhibitors. In this study, the potential toxicity of peroxovanadium complex bpV(phen) on rat pheochromocytoma PC12 cells was examined, and the mechanism by which this compound influences cell survival and/or death was explored. BpV(phen) exerted a bimodal effect on PC12 cells: survival enhancing effect at lower and death-inducing effect at higher micromolar concentrations. 1 and 3 μmol dm–3 bpV(phen) intensely induced ERK activation. In contrast, 10 and 100 μmol dm–3 bp (phen) stimulated strong and sustained JNK and p38 MAPK activation as well as caspase-3 activation that preceded bpV(phen)-induced apoptotic cell death. It is suggested that bpV(phen) might exert its action on PC12 cell survival by modulation of MAPKs and caspase-3 activation.Spojevi peroksovanadija snažni su inzulinomimetički agensi i inhibitori tirozinskih fosfataza. U ovom istraživanju ispitivana je moguća toksičnost peroksovanadijevoga kompleksa bpV(phen) na PC12 stanicama feokromocitoma štakora te način na koji ovaj spoj utječe na preživljavanje i/ili umiranje stanica. BpV(phen) dvojako je djelovao na PC12 stanice: primijenjen u nižim mikromolarnim koncentracijama poticao je preživljavanje stanica, dok su više mikromolarne koncentracije poticale umiranje stanica. 1 i 3 μmol dm–3 bpV(phen) snažno je inducirao aktivaciju ERK kinaza. Suprotno tome, 10 i 100 μmol dm–3 bpV(phen) stimulirao je snažnu i dugotrajnu aktivaciju JNK i p38 MAPK kinaza te aktivaciju kaspaze-3, što je prethodilo umiranju stanica procesom apoptoze. Pretpostavlja se da bpV(phen) djeluje na preživljavanje PC12 stanica na način da modulira aktivaciju MAPK kinaza i kaspaze-3