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Association of ABCG2 c.421C>A (rs2231142) polymorphism with atorvastatin adverse reactions
No full textStatini su jedni od najpropisivanijih lijekova današnjice, često kao dio kronične politerapije u
kardiovaskularnih pacijenata. Usprkos opravdanom statusu statina kao sigurnih lijekova, neželjene
učinke terapije nužno je prevenirati kako bi se osigurala adherencija, posebice kod terapija u cilju
prevencije kardiovaskularnih događaja. Atorvastatin, supstrat ABCG2 prijenosnika, podložan je
varijabilnoj farmakokinetici u onih s njegovom izmijenjenom ekspresijom. Varijanta p.Q141K
(c.421C>A, rs2231142) povezana je sa smanjenom ekspresijom proteina. To vodi do povećane
koncentracije njegovih supstrata uslijed povećane apsorpcije i nemogućnosti izlučivanja izvan
stanica na čijim je membranama ABCG2 prijenosnik. Polimorfizam ovog farmakogena mogao bi
objasniti o dozi ovisne nuspojave atorvastatina povezane s muskuloskeletnim sustavom i akutne
manifestacije jetrenih oštećenja te ostalo rijeđe uočene nuspojave. CPIC smjernice za propisivanje
statina tiču se SLCO1B1 gena, prvog gena čija je važnost u farmakokinetici ove skupine lijekova
prepoznata. Do danas, utjecaj polimorfizama ABCG2 gena ustanovljen je u slučaju doziranja
rosuvastatina i alopurinola gdje se preporučuju niže, odnosno više doze u onih s uočenim
varijantnim alelom A.
U ovom je diplomskom radu provedena case-control studija s ciljem evaluacije asocijacije
neželjenih učinaka i polimorfizama gena ABCG2. Genotipizacija ABCG2 c.421C>A ukupno 223
ispitanika koji su primali atorvastatin kao dio terapije različitih kardiovaskularnih i metaboličkih
bolesti učinjena je metodom TaqMan® DME. Ispitanici su dihotomizirani (slučajevi vs kontrole) s
obzirom na to jesu li iskusili nuspojave nakon primjene atorvastatina. Pokazana je statistički
značajna povezanost ABCG2 c.421C>A polimorfizma s prijavljivanim nuspojavama (p=0,0416).
Nove spoznaje na području farmakogenomike pomažu u procjeni rizika i koristi kod propisivanja
atorvastatina, što vodi korak bliže personaliziranoj medicini.Statins are among the most prescribed drugs today, often as part of chronic polytherapy in
cardiovascular patients. Despite the justified status of statins as safe drugs, it is necessary to
prevent their side effects in order to ensure adherence, especially in therapies aimed at preventing
cardiovascular events. Atorvastatin, a substrate of the ABCG2 transporter, is subject to variable
pharmacokinetics in individuals with altered expression of this transporter. The p.Q141K variant
(c.421C>A, rs2231142) is associated with reduced protein expression. This leads to increased
concentrations of its substrates due to increased absorption and the inability to be excreted outside
of cells where the ABCG2 acts as an efflux pump. The polymorphism of this pharmacogene could
explain the dose-dependent side effects of atorvastatin associated with the musculoskeletal system,
acute manifestations of liver damage, and other less common side effects. CPIC guidelines for
statin prescribing relate to the SLCO1B1 gene, the first gene whose importance in the
pharmacokinetics of this drug class has been recognized. To date, the influence of ABCG2 gene
polymorphisms has been established in the case of rosuvastatin and allopurinol dosing, where
lower and higher doses are recommended in individuals with the observed variant allele A,
respectively.
In this thesis, a case-control study was conducted to evaluate the association between adverse
effects and ABCG2 gene polymorphisms. Genotyping of ABCG2 c.421C>A was performed using
the TaqMan® DME method on a total of 223 participants receiving atorvastatin as part of therapy
for various cardiovascular and metabolic diseases. The participants were dichotomized (cases vs.
controls) based on whether they experienced side effects after taking atorvastatin or not. A
statistically significant association between the ABCG2 c.421C>A polymorphism and reported
side effects was demonstrated. Novel findings in the field of pharmacogenomics assist in assessing
the risk and benefits of prescribing atorvastatin, bringing us ones step further towards personalized
medicine
Povezanost uporabe psihofarmaka i recidivirajućih Clostridioides difficile infekcija
No full textCilj istraživanja: Clostridioides difficile infekcije predstavljaju rastući globalni problem te
sukladno tome postoji potreba za pronalaskom novih potencijalnih pacijenata s povećanim
rizikom od infekcije. S obzirom na raširenu uporabu psihofarmaka te njihove raznovrsne
mehanizme djelovanja i učinke u gastrointestinalnom sustavu, cilj istraživanja je ispitati
povezanost upotrebe psihofarmaka i pojave recidivirajućih Clostridioides difficile infekcija.
Ispitanici i metode: Provedeno je retrospektivno kohortno istraživanje u koje su uključeni
ispitanici stariji od 60 godina, a koji su hospitalizirani u Klinici za infektivne bolesti „Dr. Fran
Mihaljević“ u Zagrebu u razdoblju od 2016. do 2019. godine radi prve epizode CDI. Kohorta
ispitanika je podijeljena u dvije skupine: bolesnici koji nisu rehospitalizirani radi rCDI unutar
tri mjeseca od otpusta i oni koji jesu hospitalizirani radi rCDI unutar tri mjeseca od prve
epizode. Prikupljeni su potrebni klinički, laboratorijski i mikrobiološki podatci o bolesnicima
iz kartona bolesnika, a psihofarmaci su u svrhu ovog istraživanja podijeljeni u šest skupina.
Rezultati: U studiju je bilo uključeno ukupno 305 ispitanika, od kojih su 180, tj., 59% žene,
prosječne dobi 78 godina (IQR (interquartile range) 71- 83 godine). Unutar cijele kohorte, 106
(34,8%) pacijenata je razvilo recidivirajuću CDI unutar 90 dana od hospitalizacije ili od
završetka terapije za prvu epizodu (ukupno je zabilježeno 171 epizoda CDI). Od navedenih
pacijenata, 76 je razvilo rCDI do 28., a 99 do 90. dana. Psihofarmake u kroničnoj terapiji
upotrebljava značajan broj pacijenata od ukupnog broja ispitanika (59,8% naspram 62,3%),
podjednako i u jednoj i u drugoj skupini. Nije utvrđena razlika u upotrebi psihofarmaka između
bolesnika koji su razvili rCDI u usporedbi s onima koji su imali samo jednu epizodu CDI.
Zaključak: Ovo istraživanje nije pronašlo statistički značajnu povezanost uporabe
psihofarmaka i recidivirajućih C. difficile infekcija, međutim, psihofarmaci su vrlo kompleksna
skupina lijekova čija je uporaba iznimno raširena, a nova saznanja o utjecaju mikrobioma na
središnji živčani sustav i obrnuto upućuju na važnost novih istraživanja.Objectives: Clostridioides difficile infections represent a growing global problem, and
accordingly there is a need to find new potential patients with an increased risk of infection.
Considering the widespread use of psychotropic drugs and their various mechanisms of action
and effects in the gastrointestinal system, the aim of the study is to examine the connection
between the use of psychotropic drugs and the occurrence of recurrent Clostridioides difficile
infections.
Patients and Methods: A retrospective cohort study was conducted, which included subjects
over the age of 60, who were hospitalized at the Clinic for Infectious Diseases "Dr. Fran
Mihaljević" in Zagreb in the period from 2016 to 2019 for the first episode of CDI. The patient
cohort consists of patients in two groups: those who were not rehospitalized for rCDI within
three months of discharge and those who were hospitalized for rCDI within three months of the
first episode. The necessary clinical, laboratory and microbiological data on the patients were
collected from the patient records, and psychotropic drugs were divided into six groups for the
purpose of this research.
Results: A total of 305 subjects were included in the study, of which 180, i.e., 59% were
women, with an average age of 78 years (IQR (interquartile range) 71-83 years). Within the
entire cohort, 106 (34.8%) patients developed recurrent CDI within 90 days of hospitalization
or completion of therapy for the first episode (a total of 171 CDI episodes). Of these patients,
76 developed rCDI by day 28, and 99 by day 90. Psychopharmaceuticals are used in chronic
therapy by a significant number of patients out of the total number of respondents (59.8% vs.
62.3%), equally in one and the other group. No difference was found in the use of psychotropic
drugs between patients who developed rCDI compared to those who had only one episode of
CDI.
Conclusion: This research did not find a statistically significant association between the use of
psychotropic drugs and recurrent C. difficile infections, however, psychotropic drugs are a very
complex drug group whose use is extremely wide, and new knowledge about the influence of
the microbiome on the central nervous system and vice versa points to the importance of new
research
Development of cappilary electrophoretic method for analysis of ribociclib
No full textRibociklib je relativno novi antineoplatični lijek registriran 2017. godine koji se koristi u politerapiji u liječenju HR+/HER2- lokalno uznapredovalog ili metastatskog karcinoma dojke u kombinaciji s hormonskom terapijom, inhibitorom aromataze ili fulvestrantom.
Cilj ovog istraživanja bio je razviti novu, brzu, jednostavnu i ekološki prihvatljivu elektroforetsku metodu za analizu novog citostatika ribocikliba. S obzirom na bazični karakter ribocikliba, kao prikladna tehnika odabrana je zonska kapilarna elektroforeza uz dodatak unutarnjeg standarda diazepama. Analiza je provedena u kapilari efektivne duljine 30 cm, unutarnjeg promjera 50 μm, pri 20 °C.
Ispitan je SDS u kombinaciji s boratnim puferom (pH 9,18) i sa fosfatnim puferom (pH 2,5) te čisti fosfatni pufer. Uz boratni pufer bez dodatka SDS-a nije bilo moguće dobiti pik ribocikliba jer molekula ribocikliba pri takvom pH nije nabijena te je koeluirala s EOF. Smanjenjem koncentracije SDS-a u kombinaciji s fosfatnim puferom poboljšavao se oblik i simetrija pika. Optimalnim za analizu pokazao se fosfatni pufer pH 2,5 koncentracije 40 mM, bez dodatka SDS-a pri kojoj je postignuta najveća učinkovitost analize i dobivena najveća površina pikova, a postignuto zadovoljavajuće vrijeme analize i izbjegnuto Jouleovo zagrijavanje. Korištenjem napona 25 kV dobivena je dobra simetrija, površina i razlučivanje uz kratko vrijeme analize, a optimalnom temperaturom za analizu pokazala se temperatura od 20 ºC.
Kapilarna elektroforeza nova je analitička tehnika koja zbog mnogih prednosti (kratko vrijeme analize, mogućnost analize različitih vrsta analita, ekološka prihvatljivost, niski troškovi, jednostavnost i automatiziranost) ima veliki potencijal za primjenu u kliničkoj praksi te bi ju kao takvu metodu trebalo više koristiti kao alternativu ostalim skupljim i ekološki manje prihvatljivim analitičkim tehnikama.Ribociclib is a relatively new antineoplastic drug that is used in polytherapy in the treatment of HR + / HER2- locally advanced or metastatic breast cancer in combination with hormone therapy, aromatase inhibitor or fulvestrant.
The main goal of this study was to develop a new, fast, simple, sensitive and ecologically acceptable electrophoretic method for the analysis of a new cytostatic drug ribociclib. Given the basic character of ribociclib, capillary zone electrophoresis has proven to be the most appropriate method. The analysis was carried out in a capillary with an effective length of 30 cm, an inner diameter of 50 μm, at 20 ° C.
In this study, different buffer combinations were tested: SDS in combination with borate buffer (pH 9.18), SDS with phosphate buffer (pH 2.5) and pure phosphate buffer. While using the pure phosphate buffer without addition of SDS, it was not possible to obtain a ribociclib peak because the ribociclib molecule was not charged at such pH and it eluted at the same time as EOF. Decreasing the SDS concentration in combination with phosphate buffer improved peak shape and symmetry. Phosphate buffer (pH 2.5) without addition of SDS, with a concentration of 40 mM has proven to be optimal for analysis, at which the highest analysis efficiency was achieved and the highest peak area was obtained, while satisfactory analysis time was achieved and Joule heating was avoided. Using a voltage of 25 kV, good symmetry, surface area and resolution were obtained with a short analysis time, and the optimal temperature for the analysis was 20 ºC.
Capillary electrophoresis is a new analytical technique which due to many advantages (short analysis time, possibility of analysis of different types of analytes, environmental acceptability, low costs, simplicity and automation) has great potential for application in clinical practice. Because of that, it should be used more in drug analysis, as an alternative to other, more expensive and less environmentally friendly analytical techniques
Synthesis and characterization of hybrids of 3-substituted beta-carbolines and ferrocenes linked by 1,2,3-riazole ring
No full textU ovom radu sintetizirana su i strukturno karakterizirana 2 nova hibridna spoja koji u svojoj strukturi
sadrže β-karbolinski prsten i ferocen, povezane 1H-1,2,3-triazolom, kao i prekursori potrebni za njihovu
sintezu, b-karbolinski azid 4 i b-karbolinski alkin 6, te ferocenazid 7, dok je etinilferocen nabavljen iz
komercijalnih izvora. b-karbolinski azid sintetiziran je u četiri reakcijska koraka. Pictet-Spenglerovom
kondenzacijom metilnog estera L-triptofana i acetaldehid-dimetil-acetala nastaje tetrahidro-bkarbolinski
međuprodukt 1 koji je oksidiran (aromatiziran) u odgovarajući b-karbolin s esterskom
skupinom na položaju 3. Redukcijom estera nastaje primarni alkohol koji je uz pomoć ADMP-a kao
donora azidne skupine uz DBU preveden u b-karbolinski azid 4. Sinteza alkina u položaju C3 β-
karbolinskog prstena nastavlja se od primarnog alkohola 3. Oksidacijom alkohola te reakcijom nastalog
aldehida i Bestmann-Ohirinog reagensa nastaje b-karbolinski alkin 6. Ferocenazid 7 je sintetiziran u
jednom reakcijskom koraku. Alkololna skupina ferocenmetanola se prevodi u azido uz ADMP u
bazičnim uvjetima. Za povezivanje b-karbolinskog azida 4 i etinilferocena, te b-karbolinskog alkina 6 i
ferocenazida 7 u hibridne spojeve 8 i 9, korištena je bakrom (I) katalizirana azid-alkin cikloadicija koja
rezultira stvaranjem triazolskog prstena, poveznice između b-karbolinskog prstena i ferocena. Strukture
sintetiziranih spojeva potvrđene su spektroskopskim i spektrometrijskim metodama (1H i 13C NMR, IR,
MS). U daljnjim istraživanjima bit će ispitano biološko djelovanje sintetiziranih hibridnih spojeva.Two new hybrid compounds, 8 and 9, consisting of β-carboline and ferrocene moieties, connected via
1H-1,2,3-triazole, have been synthesized and structurally characterized, as well as precursors required
for their synthesis, b-carboline azide 4, b-carboline alkyne 6, and ferrocenazide 7, while
ethynylferrocene was obtained from commercial sources. b-carboline azide has been sythesized in a
four steps procedure. Pictet-Spengler condensation of L-tryptophan with ADMA generated tetrahydrob-
carboline intermedier 1 which was subsequently oxidized to corresponding b-carboline ester 2.
Reduction of the ester gave the corresponding alcohol 3 which was converted to b-carboline azide 4 by
using ADMP under basic conditions (DBU). The synthesis of alkyne at the C3 position of the bcarboline
ring involves oxidation of the alcohol 3 to the aldehyde 5. Homologation of aldehyde with
dimethyl (1-diazo-2-oxopropyl) phosphonate in the presence of K2CO3 resulted in b-carboline alkyne 6.
Ferrocenazide 7 was synthesized in a one reaction step. The alcohol group of ferrocenmethanol was
converted to the azido using ADMP in the presence of DBU. The copper(I)-catalyzed azide-alkyne
cycloaddition was used as a method of choice for linking b-carboline azide 4 and ethynylferrocene or
β-carboline alkyne 6 and ferrocenazide 7, into hybrid compounds 8 and 9, respectively. As a result, a
triazole ring was formed. The structures of the prepared compounds were confirmed by analytical and
spectroscopic methods (1H and 13C NMR, IR, MS). In further studies, the biological activity of the
synthesized hybrid compounds, will be investigated
Development of capillary electrophoretic method for anastrozole analysis
No full textZbog velike učestalosti raka dojke u populaciji i razvoja različitih terapijskih mogućnosti liječenja ove bolesti, od iznimne je važnosti razvoj novih analitičkih metoda za terapijsko praćenje liječenja odabranim lijekovima.
Cilj je ovog istraživanja bio razviti brzu i jednostavnu kapilarnoelektroforetsku metodu za analizu anastrozola koja će uz to biti ekološki prihvatljivija i jeftinija od već uvažene HPLC metode. Kao prikladna tehnika odabrana je micelarna elektrokinetička kromatografija.
Analiza je provedena na kapilari od izvučenog kvarca duljine 35 cm, duljine puta do detektora od 27 cm i unutrašnjeg promjera 50 μm. Uzorci su hidrodinamički injektirani u kapilaru pod tlakom od 50 mbar, pri temperaturi od 20°C u vremenu od 4 sekunde. Valna duljina od 210 nm korištena je za detekciju anastrozola.
Promatran je utjecaj koncentracije boratnog pufera (15 – 45 mM) i SDS-a (15 – 50 mM) te temperature (17,5 – 27,5 °C) i napona (22,5 – 30 kV) na vrijeme analize, površinu pika te broj teorijskih tavana. Kao optimalne vrijednosti uzete su 20 mM boratni pufer, 45 mM SDS i temperatura od 20 °C.
Predlaže se daljnja optimizacija metode uz nižu koncentraciju anastrozola cijepljenog u plazmi. Predmet daljnjeg istraživanja bit će optimizacija uvjeta istovremene analize anastrozola i lijekova s kojima se on koristi u kombiniranoj terapiji za liječenje uznapredovalog hormonski ovisnog tumora dojke negativnog na HER2: palbocikliba, ribocikliba ili abemacikliba.Considering the high incidence of breast cancer that is present in our population and the development of various treatment options for this disease, it is of great importance to develope new analytical methods for therapeutic drug monitoring of the drugs of interest.
The aim of this study was to develop a fast and simple capillary electrophoretic method for the analysis of anastrozole, which will also be more environmentally friendly and cheaper than the already respected HPLC method. Micellar electrokinetic chromatography was selected as a suitable technique.
This analysis was performed on a 35 cm long capillary of fused silica, with effective length of 27 cm, and an inner diameter of 50 μm. The samples were hydrodynamically injected into the capillary under 50 mbar pressure, at a 20 °C temperature for 4 seconds. A wavelength of 210 nm was used to detect anastrozole.
The effects of borate buffer (15 – 45 mM) and SDS (15 – 50 mM) concentration, as well as temperature (17.5 – 27.5 °C) and voltage (22.5 – 30 kV) on the migration time, peak area, and theoretical plates were observed. Considering the experimental results, 20 mM borate buffer, 45 mM SDS, and a temperature of 20 ° C were taken as optimal values.
It is required to further optimize this method using a lower concentration of anastrozole spiked in plasma. The subject of further research will also be the optimization of conditions in simultaneous analysis of anastrozole and other drugs that are used as a combination therapy for treatment of advanced hormone-dependent HER2 - negative breast cancer: palbocyclib, ribocyclib or abemacyclib
Gamma irradiation resistance of Cladosporium sphaerospermum
No full textPredmeti kulturne baštine na papiru predstavljaju značajan dio kulturne baštine pohranjen u
knjižnicama i muzejima. Pogodni su za rast i razvoj mikroorganizama koji uzrokuju fizikalna,
kemijska i biološka oštećenja. Plijesan Cladosporium sphaerospermum čest je kolonizator
papirnih dokumenata i slika te uzrokuje njihovo propadanje zbog mogućnosti da prodre duboko u
materijal gdje dovodi do enzimske degradacije i posljedično mehaničke razgradnje. Postoje
različite metode dekontaminacije predmeta od papira. Kao najučinkovitija i najprihvatljivija
metoda pokazalo se gama zračenje. U ovom radu ispitan je utjecaj gama zračenja u dozama od 2
kGy, 5 kGy, 10 kGy, 15 kGy i 20 kGy pri brzinama od 0,04 Gy/s, 0,1 Gy/s, 0,2 Gy/s, 0,4 Gy/s i
6,7 Gy/s na inhibiciju rasta vrste Cladosporium sphaerospermum neposredno nakon zračenja.
Kladosporija se pokazala visoko rezistentnom budući da je preživjela i najveće doze zračenja (20
kGy) pri nižim brzinama. Iz rezultata je vidljivo da se povećanjem doze proporcionalno smanjuje
otpornost kladosporije prema zračenju i pri nižim brzinama. Decimalna redukcijska doza – D10
pri brzini od 0,04 Gy/s iznosi 9,9 kGy; pri brzini od 0,1 Gy/s iznosi 16 kGy; pri brzini od 0,2 Gy/s
iznosi 4,77 kGy; pri brzini od 0,4 Gy/s iznosi 1,93 kGy; te pri brzini od 6,7 Gy/s iznosi 1 kGy.
Potrebno je provesti ispitivanja mogućeg oporavka plijesni nekoliko mjeseci i godina nakon
zračenja. Također, potrebno je proučiti moguće promjene kemijskih i fizikalnih svojstava papira
budući da gama zračenje izravno uzrokuje degradaciju materijala.Paper-based materials represent major part of cultural heritage kept in libraries and museums.
They are suitable for growth and development of microorganisms and they cause physical,
chemical and biological damages. Cladosporium sphaerospermum often colonises paper-based
documents and paintings and causes their destruction due to the ability of penetration deep into
material that leads to enzymatic degradation and mechanical decomposition. There are various
decontamination methods of paper-based documents. Gamma irradiation is the most efficient and
acceptable method. The paper analyzes effects of gamma irradiation in radiation doses of 2 kGy,
5 kGy, 10 kGy, 15 kGy and 20 kGy at dose rates of 0,04 Gy/s, 0,1 Gy/s, 0,2 Gy/s, 0,4 Gy/s and
6,7 Gy/s on Cladosporium sphaerospermum immediately after irradiation. Cladosporium
sphaerospermum is highly resistant to gamma irradiation because it survived highest doses (20
kGy) at lower dose rates. The results have shown that the increase of applied doses proportionally
reduces resistance to irradiation at lower dose rates. Decimal reduction dose – D10 at dose rate of
0,04 Gy/s is 9,9 kGy; at dose rate of 0,1 Gy/s is 16 kGy; at dose rate 0,2 Gy/s is 4,77 kGy; at dose
rate 0,4 Gy/s is 1,93 kGy; at dose rate 6,7 Gy/s is 1 kGy. Further testing of possible recovery of
moulds several months and years after the irradiation is required. Additionally, new studies of
possible changes in chemical and physical properties of paper are needed, because gamma
irradiation directly causes material degradation
Sigurnost primjene antipsihotika u trudnoći
No full textCilj istraživanja: Cilj ovog rada je utvrditi sigurnost, učinkovitost, prednosti i nedostatke korištenja antipsihotika u trudnoći s naglaskom na najčešće korištene atipične antipsihotike.
Materijali i metode: Pri izradi specijalističkog rada bit će napravljen sustavni pregled znanstvene i stručne literature. Bit će pretražene trenutno važeće terapijske smjernice za liječenje shizofrenije i drugih psihotičnih poremećaja, publikacije stručnih udruga i institucija te baza lijekova Agencije za lijekove i medicinske proizvode.
Rezultati: Identificirane su i na jednom mjestu pregledno prikazane glavne specifičnosti primjene svih antipsihotika prve i druge generacije u trudnoći registriranih u Hrvatskoj.
Zaključak: Sa sigurnosnog gledišta, značajna i umirujuća količina podataka o antipsihoticima druge generacije općenito ne sugerira klinički značajan povećani rizik od kongenitalnih malformacija. Iako nisu značajno povećani rizici od kongenitalnih malformacija, podaci o drugim ishodima trudnoće od interesa, tj. spontani pobačaj, mrtvorođenje, prijevremeni porod, mala težina za gestacijsku dob, neonatalna prilagodba i neurorazvoj u djetinjstvu, općenito su nedostatni za pružanje pouzdanih procjena. Tipični antipsihotici prve generacije, kao i atipični ne uzrokuju povećanje stope kongenitalnih malformacija iznad populacijske norme. Prema dostupnim podacima, prva generacija antipsihotika ne predstavlja tijekom trudnoće povećan rizik od pobačaja ili mrtvorođenja. Moguće je povećanje rizika od prijevremenog poroda. Stvarni izbor lijeka za pojedinu trudnicu mora uzeti u obzir i ostale čimbenike, ne samo podatke o sigurnosti. Ključno je pažljivo razmotriti individualnu povijest bolesti, karakteristike i odgovor na liječenje, profil nuspojava i sklonosti bolesnika.Objectives: The aim of this paper is to determine the safety, effectiveness, advantages and disadvantages of using antipsychotics in pregnancy with emphasis on the most commonly used atypical antipsychotics.
Materials and methods: A systematic review of scientific and professional literature will be done during the preparation of this paper. Current therapeutic guidelines for the treatment of schizophrenia and other psychotic disorders, publications of professional associations and institutions, and the drug database of the Agency for Medicines and Medical Products will be searched.
Results: The main specificities of the use of all first and second generation antipsychotics registered in Croatia in pregnant women have been identified and presented in one place.
Conclusion: From a safety perspective, the substantial and reassuring data on atypical antipsychotics generally does not suggest significantly increased risk of congenital malformations. Although the risks of congenital malformations are not significantly increased, data on other pregnancy outcomes like miscarriage, stillbirth, preterm birth, small for gestational age, neonatal adjustment, and childhood neurodevelopment, are generally insufficient to provide reliable estimates. Typical antipsychotics, as well as atypical ones, do not cause an increase in the rate of congenital malformations above the population norm. According to the available data, they don't present an increased risk of miscarriage or stillbirth. It is possible they increase the risk of premature birth. The actual choice of drug for pregnant woman must take into account other factors, not only safety data. It is crucial to consider the individual medical history, characteristics and response to treatment, side effect profile and patient preferences achieving better treatment outcomes
Effect of high-intensity exercise on galectin-3 plasma concentration
No full textGalektin-3, lektin koji prepoznaje i veže β-galaktozidne jedinice glikokonjugata, može biti smješten u različitim dijelovima stanice ili izvan nje, eksprimiran u brojim tkivima te sudjelovati u raznovrsnim procesima u organizmu. Odnedavno je prepoznat i kao biomarker određenih patoloških stanja. Rezultati dosadašnjih malobrojnih istraživanja o učinku fizičke aktivnosti na plazmatske koncentracije galektina-3 nisu jednoznačni. U ovom radu istražen je učinak kontinuirane visokointenzivne tjelovježbe provedene tijekom šestotjednih progresivno intenzivnijih ponavljanih sprinterskih treninga na mladim i zdravim muškarcima. Uzorci krvi uzimani su u tri vremenske točke: a - prije početka eksperimentalnog protokola, b - neposredno nakon predzadnjeg i najintenzivnijeg treninga te c - mjesec dana nakon završetka protokola. Koncentracije galektina-3 izmjerene su metodom „sendvič“ ELISA, primjenom komercijalno dostupnog kita Quantikine® ELISA Human Galectin-3 Immunoassay. Statistička analiza podataka provedena je dvosmjernom analizom varijance ponovljenih mjerenja u programu GraphPad Prism 9.0.0. Niti u jednoj od tri ispitane vremenske točke, intenzivna tjelovježba nije uzrokovala statistički značajne razlike u plazmatskoj koncentraciji galektina-3 između eksperimentalne i kontrolne skupine. U obje skupine uočen je sličan obrazac smanjenja koncentracije galektina-3, posebice u posljednjoj točki mjerenja (1 mjesec nakon završetka protokola) u odnosu na prvu točku (prije početka protokola). Uzrok takvog ishoda u ovom je istraživanju nepoznat, međutim, s obzirom da su i kontrolnu i eksperimentalnu skupinu činili studenti Kineziološkog fakulteta te da je tijekom istraživanja svima bila dozvoljena tjelovježba u sklopu studija, moguće je da je ta tjelovježba, koja bi se mogla klasificirati kao umjerena do intenzivna, već sama bila dostatna za postizanje uočenog učinka.Galectin-3, a β-galactoside-binding lectin, is localised within various parts of the cell and outside of
it, expressed in multiple tissues and participates in various processes within the organism. Galectin-3 has
recently been recognized as a biomarker of certain pathological states. The results of the few studies done
on the effect of physical activity on plasma concentrations of galectin-3 are not in unison. In this study, the
effect of high-intesity interval training, organised as repeated sprint training with a progressive increase in
intesity in duration of six weeks, has been investigated. The study subjects were young healthy males. The
blood samples were taken at three different time points: a – before the start of the experimental protocol, b –
immediately after the penultimate and most intense training session and c – 1 month after the end of the
experimental protocol. Galectin-3 concentrations were measured by a „sandwich“ ELISA method, using a
commercially available Quantikine® ELISA Human Galectin-3 Immunoassay kit. The statistical data
analysis was done by a two-way analysis of variance in GraphPad Prism 9.0.0. In none of the three
examined time points, intense exercise did not cause statistically significant differences in the plasma
concentration of galectin-3 between the experimental and control groups. In both groups, a similar pattern
of reduction in galectin-3 concentration was observed, especially in the last measurement point (1 month
after the end of the protocol) compared to the first (before the start of the protocol). The cause of such an
outcome in this research is unknown, however, given that both the control and experimental groups were
students of the Faculty of Kinesiology and that during the investigation everyone was allowed to exercise as
part of their studies, it is possible that this exercise, which could be classified as moderate to intense, alone
was sufficient to achieve the observed effect
Stability of citric acid in aqueous solutions. 1H NMR studyU okviru projekta koji proučava nanočestice zlata i provodi se na Institutu za medicinska istraživanja i medicinu rada u Zagrebu, provedene su dvije NMR studije na Farmaceutsko-biokemijskom fakultetu u Zagrebu. Jedna od provedenih NMR studija istražuje strukturalne promjene limunske kiseline tijekom sinteze nanočestica uz upotrebu limunske kiseline. Druga NMR studija, odnosno ovaj diplomski rad, fokusira se na ispitivanje stabilnosti limunske kiseline u vodenim otopinama pri reakcijskim uvjetima koji su prisutni tijekom sinteze nanočestica zlata. Stabilnost limunske kiseline provjerena je u uvjetima aeracije, zakiseljavanja i refluksiranja vodene otopine limunske kiseline. Snimanjem 1H NMR spektara dokazano je da u navedenim reakcijskim uvjetima nije došlo do strukturalnih promjena limunske kiseline. Iako tijekom zakiseljavanja vodene otopine limunske kiseline nije došlo do promjene u strukturi limunske kiseline, primijećen je pomak signala limunske kiseline prema području nižeg magnetskog polja. Promjena u strukturi limunske kiseline javlja se tek nakon primjene vrlo agresivnih reakcijskih uvjeta, odnosno kiselim refluksiranjem vodene otopine limunske kiseline. Tijekom refluksa zakiseljene vodene otopine limunske kiseline dolazi do kiselo katalizirane i temperaturom potpomognute dehdidratacije limunske kiseline uz zatvaranje peteročlanog anhidridnog prstena. Rezultati ovog diplomskog rada upućuju na stabilnost limunske kiseline pri reakcijskim uvjetima sinteze nanočestica zlata uz prisutnost limunske kiseline.v
No full textU okviru projekta koji proučava nanočestice zlata i provodi se na Institutu za medicinska istraživanja i medicinu rada u Zagrebu, provedene su dvije NMR studije na Farmaceutsko-biokemijskom fakultetu u Zagrebu. Jedna od provedenih NMR studija istražuje strukturalne promjene limunske kiseline tijekom sinteze nanočestica uz upotrebu limunske kiseline. Druga NMR studija, odnosno ovaj diplomski rad, fokusira se na ispitivanje stabilnosti limunske kiseline u vodenim otopinama pri reakcijskim uvjetima koji su prisutni tijekom sinteze nanočestica zlata. Stabilnost limunske kiseline provjerena je u uvjetima aeracije, zakiseljavanja i refluksiranja vodene otopine limunske kiseline. Snimanjem 1H NMR spektara dokazano je da u navedenim reakcijskim uvjetima nije došlo do strukturalnih promjena limunske kiseline. Iako tijekom zakiseljavanja vodene otopine limunske kiseline nije došlo do promjene u strukturi limunske kiseline, primijećen je pomak signala limunske kiseline prema području nižeg magnetskog polja. Promjena u strukturi limunske kiseline javlja se tek nakon primjene vrlo agresivnih reakcijskih uvjeta, odnosno kiselim refluksiranjem vodene otopine limunske kiseline. Tijekom refluksa zakiseljene vodene otopine limunske kiseline dolazi do kiselo katalizirane i temperaturom potpomognute dehdidratacije limunske kiseline uz zatvaranje peteročlanog anhidridnog prstena. Rezultati ovog diplomskog rada upućuju na stabilnost limunske kiseline pri reakcijskim uvjetima sinteze nanočestica zlata uz prisutnost limunske kiseline.Within the project focused on gold nanoparticles, conducted at the Institute for Medical Research and Occupational Health in Zagreb, two NMR studies were carried out at the Faculty of Pharmacy and Biochemistry in Zagreb. One of the conducted NMR studies investigates the structural changes of citric acid during the synthesis of nanoparticles using citric acid. The second NMR study, which is the subject of this thesis, focuses on examining the stability of citric acid in aqueous solutions under the reaction conditions present during the synthesis of gold nanoparticles. The stability of citric acid was tested under conditions of aeration, acidification, and reflux of the citric acid solution. By recording 1H NMR spectra, it was demonstrated that there were no structural changes in citric acid under the mentioned reaction conditions. Although no structural changes occurred during the acidification of the citric acid solution, a shift in the signals of citric acid towards lower magnetic field regions was observed. The change in the structure of citric acid only occurred after applying highly aggressive reaction conditions, namely, the acidic reflux of the citric acid solution. During the reflux of the acidified citric acid solution, acid-catalyzed and temperature-assisted dehydration of citric acid took place, resulting in the closure of a five-membered anhydride ring. The results of this thesis indicate the stability of citric acid under the reaction conditions of gold nanoparticle synthesis in the presence of citric acid
The association of serotonin transporter gene polymorphisms with neonatal anthropometric characteristics
No full textSerotonin je multifunkcionalna signalna molekula uključena u širok raspon fizioloških
funkcija, a posebno se ističe njegova uloga u regulaciji energijske ravnoteže organizma.
Serotoninska signalizacija u velikoj je mjeri modulirana serotoninskim transporterom,
transmembranskim proteinom kroz koji serotonin ulazi u stanicu čime se terminira serotoninski
signal. Određeni polimorfizmi gena SLC6A4 koji kodira za serotoninski transporter povezuju
se s intenzitetom transkripcije navedenog gena te s podložnosti razvoja pretilosti i povezanih
komorbiditeta. Glavni cilj istraživanja bio je pobliže ispitati potencijalnu povezanost
polimorfizama gena SLC6A4 s antropometrijskim karakteristikama novorođenčadi, uzimajući
u obzir mogući utjecaj različitih karakteristika novorođenčadi i majki. Genomska DNA
izolirana je iz tkiva posteljice, a genotipizacija promotorskog polimorfizma 5-HTTLPR te
intronskog polimorfizma STin2 provedena je pomoću lančane reakcije polimerazom (PCR),
dok je genotipizacija polimorfizma zamjene pojedinačnih nukleotida rs25531 provedena
digestijom dobivenih 5-HTTLPR PCR produkata restrikcijskom endonukleazom MspI. U
okviru istraživanja proveden je i postupak optimizacije metode koji je obuhvaćao modifikaciju
metoda PCR i agarozne gel elektroforeze. Utvrđene frekvencije genotipova i alela analiziranih
polimorfizama bile su u skladu s dosad zabilježenom distribucijom u hrvatskoj populaciji.
Opažen je statistički značajan učinak spola i gestacijske dobi novorođenčadi na porođajnu masu
i duljinu, ali ne i na ponderalni indeks. Zabilježena je statistički značajna razlika u ponderalnom
indeksu između novorođenčadi različitog genotipa za polimorfizam STin2, u ukupnom uzroku
i u skupini ženske, ali ne i muške novorođenčadi. Razumijevanje bioloških i ostalih čimbenika
koji utječu na antropometrijske karakteristike novorođenčadi moglo bi doprinijeti razvoju
programa rane intervencije i prevencije metaboličkih poremećaja i pratećih komorbiditeta
tijekom daljnjeg životnog vijeka.Serotonin is a multifunctional signaling molecule involved in a wide range of
physiological functions, with a particularly prominent role in regulating the body's energy
balance. Serotonin signaling is largely modulated by the serotonin transporter, a transmembrane
protein through which serotonin enters the cell, what leads to termination of the serotonin
signaling. Certain polymorphisms of the SLC6A4 gene, coding for the serotonin transporter, are
associated with the intensity of transcription of this gene and with its susceptibility to the
development of obesity and related comorbidities. The main goal of this study was to
investigate the potential association of SLC6A4 gene polymorphisms with neonatal
anthropometric characteristics, taking into account the possible influence of different neonatal
and maternal characteristics. Genomic DNA was isolated from placental tissue and genotyping
of the 5-HTTLPR promoter polymorphism and STin2 intron polymorphism was performed by
polymerase chain reaction (PCR), while genotyping of the single nucleotide polymorphism
rs25531 was performed by digestion of the obtained 5-HTTLPR PCR products with restriction
endonuclease MspI. A method optimisation procedure was carried out as part of the study,
which included modification of the PCR and agarose gel electrophoresis methods. The
determined frequencies of the genotypes and alleles of the analyzed polymorphisms were in
accordance with the previously observed in the Croatian population. A statistically significant
effect of sex and gestational age of the newborns on birth weight and length, but not on the
ponderal index, was observed. A statistically significant difference in the ponderal index was
found between newborns of different genotypes for the STin2 polymorphism, both in the total
sample and in the group of female, but not male newborns. Understanding the underlying
influence of biological and other factors on the neonatal anthropometric characteristics could
contribute to the development of programs of early intervention and prevention of metabolic
disorders and accompanying comorbidities later in life