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The use of topical retinoids in skin photoaging
No full textStarenje kože je multisistemski proces koji započinje sredinom dvadesetih godina. Razlikuje se
intrinzično i ekstrinzično starenje. Intrinzično (kronološko) starenje je prirodan proces, dok je
ekstrinzično uvjetovano vanjskim čimbenicima te se često naziva i fotostarenje. Fotostarenje kože
je izravno u korelaciji s izlaganjem UV zračenju tijekom života te se uglavnom ispoljava prije nego
kronološko starenje. Fotooštećenu kožu karakteriziraju hiperpigmentacijske mrlje, opadanje razine
kolagena i elastina te bore. Pojedincima koji više vremena provode na otvorenom, svijetle su puti ili
pak žive u sunčanom podneblju koža brže stari. Kako bi se preveniralo oštećenje kože uzrokovano
UV zračenjem koriste se proizvodi sa zaštitnim faktorom. Razlikuju se proizvodi s kemijskim i
mineralnim filterima koji se mogu naći u različitim kozmetičkim oblicima (npr. krema, fluid, losion,
mlijeko). U svrhu prevencije i usporavanja fotostarenja koriste se proizvodi koji sadrže vitamin C,
azelaičnu kiselinu te retinoide. Studije potvrđuju kako su kod fotostarenja najučinkovitiji retinoidi.
Najviše se koriste tretinoin, retinol i retinal. Potrebno ih je uvoditi s oprezom zbog moguće
retinoidne reakcije koju karakteriziraju svrbež, crvenilo i ljuskanje kože. Trudnicama, dojiljama i
ženama koje planiraju trudnoću ne preporuča se korištenje retinoida zbog teratogenog djelovanja te
se sugerira korištenje glikolne kiseline, vitamina C te bakuchiola.Skin aging is a multisystemic process that begins in the mid-twenties. We differentiate intrinsic and
extrinsic aging. Intrinsic (chronological) aging is a natural process, while extrinsic aging is
conditioned by external factors and is often called photoaging. Photoaging of the skin is directly
correlated with the amount of UV rays exposed during life and is generally manifested earlier than
chronological aging. Photodamaged skin is characterized by hyperpigmentation spots, decreasing
levels of collagen and elastin, and wrinkles. Individuals's skin who spend more time outside, have
fair skin, or live in sunny climates ages faster. In order to prevent skin damage caused by UV rays,
products with a protective factor are used. We distinguish between products with chemical and
mineral filters that can be found in different cosmetic forms (eg cream, fluid, lotion, milk, etc.). In
order to prevent and treat photoaging, products containing vitamin C, azelaic acid and retinoids are
used. Studies confirm that retinoids are the most effective in photoaging. The most commonly used
are tretinoin, retinol and retinal. They should be introduced with caution due to a possible retinoid
reaction characterized by itching, redness and scaling of the skin. Pregnant women, lactating women
and women planning to become pregnant are advised to avoid the use of retinoids due to their
teratogenic effect, and the use of glycolic acid, vitamin C and bakuchiol is suggested
Valorization of tomato pomace as a source of antioxidants
No full textKomina rajčice je otpadni materijal procesuiranja rajčice te se sastoji od pokožice, koštica i ostataka usplođa.
Dosadašnja istraživanja potvrdila su prisutnost fenolnih spojeva s visokom antioksidativnom aktivnošću koja
omogućavaju valorizaciju komine rajčice za proizvodnju nutraceutika, odnosno spojeva s dodanom
vrijednošću uz istodobno rješavanje problema odlaganja bio-otpada. Biološki aktivne komponente komine
rajčice, prvenstveno karotenoidi i fenolni spojevi ispoljavaju protuupalno, antimutageno i antikancerogeno
djelovanje. Ovaj diplomski rad istražuje utjecaj različitih vrsta sušenja (sušenje u termostatu na 70°C i sušenje
smrzavanjem) na sadržaj bioaktivnih sastavnica s antioksidativnim djelovanjem te uspoređuje udio navedenih
sastavnica u različitim dijelovima komine rajčice (cjelokupna komina, pokožica i koštice). Određivanje
ukupnih fenola provedeno je Folin-Ciocalteu metodom, zatim je TEAC metodom određena sposobnost
vezanja radikala te je ORAC metodom izmjerena antioksidacijska učinkovitost. Iz dobivenih rezultata
proizlazi kako postupak sušenja značajno utječe na udio polifenola, tj. sušenje komine rajčice u termostatu
na 70°C predstavlja bolju opciju za očuvanje antioksidativnog potencijala u odnosu na sušenje komine rajčice
smrzavanjem. Dokazana je korelacija između udjela polifenola i antioksidativnog potencijala. Također
potvrđeno je kako pokožica rajčice sadrži značajno veću količinu polifenolnih spojeva s antioksidativnom
aktivnošću od koštice rajčice. Rezultati mogu doprinijeti postojećim saznanjima o komini rajčice kao vrijedne
sekundarne sirovine za njeno bolje iskorištavanje u vidu dobivanja bioaktivnih sastavnica s antioksidativnim
djelovanjem.Tomato pomace is a waste material from the processing of tomatoes and consists of the skin, seeds and
remains of the pulp. Previous research has confirmed the presence of phenolic compounds with high
antioxidant activity that enable the valorization of tomato pomace for the production of nutraceuticals, i.e.
compounds with added value while also solving the problem of bio-waste disposal. Biologically active
components of tomato pomace, primarily carotenoids and phenolic compounds exhibit anti-inflammatory,
antimutagenic and anticancer effects. This diploma thesis investigates the influence of different types of
drying (drying in a thermostat at 70°C and freeze drying) on the content of bioactive components with
antioxidant activity and compares the proportion of said components in different parts of tomato pomace
(whole pomace, skin and seeds). Total phenols were determined using the Folin-Ciocalteu method, radical
binding capacity was determined using the TEAC method, and antioxidant efficiency was measured using
the ORAC method. The obtained results show that the drying process significantly affects the content of
polyphenols, i.e. drying tomato pomace in a thermostat at 70°C is a better option for preserving the antioxidant
potential compared to drying tomato pomace by freezing. A correlation between the content of polyphenols
and antioxidant potential has been proven. It was also confirmed that the skin of the tomato contains a
significantly higher amount of polyphenolic compounds with antioxidant activity than the seeds of the tomato.
The results can contribute to existing knowledge about tomato pomace as a valuable secondary raw material
for its better utilization in the form of obtaining bioactive components with antioxidant activity
Drug-related problems at hospital admission in older patients with cardiology diseases
No full textKronične, nezarazne bolesti, među kojima su najčešće kardiovaskularne bolesti (KVB), vodeći su uzrok smrtnosti i pobola u svijetu. Od čimbenika
rizika za razvoj KVB-a najvažniji su hipertenzija, hiperlipidemija, pretilost, nepravilna prehrana, pušenje, tjelesna neaktivnost i šećerna bolest.
Prema najnovijim podacima, osobe starije životne dobi (stariji od 65 godina) čine petinu stanovništva Europske unije. Starenjem dolazi do
progresivnog oštećenja više organa, zbog čega se mijenja farmakokinetika i farmakodinamika brojnih lijekova i povećava rizik neželjenih
djelovanja lijekova. Zbog multimorbiditeta kod starijih osoba raste potrošnja lijekova i nastanak terapijskih problema tijekom liječenja. Cilj ovog
istraživanja bio je utvrditi učestalost i vrstu politerapije, potencijalno neprikladnih lijekova, klinički značajnih interakcija između lijekova i rizičnih
lijekova s obzirom na oslabljenu bubrežnu funkciju primjenom „najbolje moguće povijesti lijekova“ (BPMH). Također, za svaki od navedenih
terapijskih problema cilj je bio utvrditi zastupljenost lijekova s djelovanjem na kardiovaskularni sustav. U istraživanju je sudjelovalo 105 ispitanika
u dobi ≥ 65 godina zaprimljenih u KB Dubrava, Zavod za bolesti srca i krvnih žila. Politerapija je definirana kao istovremena primjena 5-9 lijekova,
dok se primjena ≥ 10 lijekova definirala kao pretjerana politerapija. Potencijalno neprikladni lijekovi (PNL-ovi) određeni su primjenom EU(7)-PIM
kriterija. Potencijalno klinički značajne interakcije su analizirane pomoću softverskog programa Lexicomp® koji svrstava interakcije u 5 kategorija
prema kliničkom značaju (A, B, C, D, X). Analiza rizičnih lijekova kod oslabljene bubrežne funkcije provedena je kod pacijenata s eGFR < 60
ml/min/1,73 m2
(KDIGO stadiji G3a, G3b, G4 i G5), korištenjem sažetaka opisa svojstava lijekova (HALMED). Istraživanje je utvrdilo prisutnost
politerapije kod 56,2% ispitanika, dok je 27,6% njih uzimalo ≥ 10 lijekova. PNL-ovi su utvrđeni kod 74,3% ispitanika, od čega je 20,7% lijekova
uključenih u PNL-ove pripadalo ATK skupini C. Kod 93,3% pacijenata utvrđena je najmanje jedna potencijalno klinički značajna interakcija.
Primjenom BPMH utvrđeno je 35 rizičnih lijekova kod oslabljene bubrežne funkcije, od čega je čak 62,9% lijekova pripadalo ATK skupini C.
Dobiveni podaci ukazuju na važnost primjene BPMH i usklađivanja terapije pri prijelazima skrbi kako bi se osigurala što bolja i sigurnija skrb za
pacijenta.Chronic, non-communicable diseases, among which cardiovascular diseases (CVD) are the most common, are the leading cause of mortality and
morbidity in the world. Among the risk factors for CVD, the most important are hypertension, hyperlipidemia, obesity, poor eating habits, tobacco
smoking, physical inactivity and diabetes mellitus. According to the latest data, older adults (over 65 years old) make up a fifth of the population of
the European Union. Aging leads to progressive loss of organ function over time, which changes the pharmacokinetics and pharmacodynamics of
numerous drugs and increases the risk of adverse drug events. Due to multimorbidity in the older patients, the consumption of drugs and the
emergence of drug-related problems during treatment is increasing. The aim of the study was to evaluate the prevalence of polypharmacy,
potentially inappropriate medications (PIMs), clinically significant interactions between drugs (DDIs) and inappropriately prescribed renal risk
drugs (RRDs) using the "best possible medication history" (BPMH). Additional aim was to determine the prevalence of cardiovascular drugs among
identified drug-related problems. The study included 105 subjects aged 65 years or older, admitted to KB Dubrava, Institute for Heart and Blood
Vessel Diseases. Polypharmacy was defined as the simultaneous use of 5-9 drugs, while the use of 10 drugs and more was defined as
hyperpolypharmacy. The EU(7)-PIM criteria were applied for PIMs detection. Potential DDIs were detected using Lexicomp software that
categorizes DDIs into five categories according to clinical significance (A, B, C, D, X). The analysis of inappropriately prescribed renal risk drugs
was performed in patients with eGFR < 60 ml/min/1.73 m2 (KDIGO stages G3a, G3b, G4 and G5), using Summary of Product Characteristics
(HALMED). The research determined the presence of polypharmacy in 56,2% of patients, while 27,6% of them used 10 or more medications. PIMs
were found in 74,3% of patients, of which 20,7% were drugs belonging to Anatomical Therapeutic Chemical classification (ATC) group C. At least
one potential clinically significant interaction was found in 93,3% of patients. 35 renal risk drugs were detected in patients with renal impairment by
using BPMH, of which 62,9% of drugs belonged to ATC group C. The obtained data highlights the importance of using the BPMH and optimise
therapy during transitions of care in order to ensure patient safety
N-glycosylation of immunoglobulin A depending on the age and gender of a subject
No full textPromjene u procesu N-glikozilacije glikana vezanih na imunoglobulin A dokazano modificiraju djelovanje imunološkog
sustava budući da glikani sudjeluju u procesu smatanja i transporta proteina, ali i izvršavanja funkcije proteina
unutarstaničnom i izvanstaničnom signalizacijom. Obzirom da je N-glikozilacija imunoglobulina A do sada neistražena,
ciljevi ovog diplomskog rada bili su 1) analizirati N-glikozilaciju IgA kod 84 zdrava ispitanika, 2) ispitati ponašanje
pojedine glikanske strukture ovisno o dobi i spolu te 3) identificirati glikanske strukture prisutne na IgA koje se razlikuju
između žena i muškaraca u pojedinoj dobnoj skupini. Učinjena je izolacija IgA iz plazme ispitanika, deglikozilacija Nglikana te obilježavanje i pročišćivanje N-glikana, a analiza je učinjena kromatografskom tehnikom hidrofilne
interakcije s detekcijom fluorescencije (HILIC-UPLC).
Rezultati su pokazali događanje većih promjena u razini glikana niskog stupnja grananja u usporedbi s glikanima visokog
stupnja grananja (GP 23-30). Uočen je trend porasta negalaktoziliranih glikana izraženiji kod žena povećanjem dobi.
Monogalaktozilirani i digalaktozilirani glikani pokazuju trend porasta kod žena, dok se razina digalaktoziliranih glikana
smanjuje kod muškaraca s dobi. Glikanske strukture GP 8, 11, 16 i 21 pokazuju statistički značajnu razliku između žena
i muškaraca u trećoj dobnoj skupini (50-60) što se podudara sa grafičkim prikazima tendencija glikana. Stoga možemo
zaključiti da se najveće promjene razina glikana s naglaskom na ženski spol događaju u trećoj dobnoj skupini (50-60)
što se može povezati sa ulaskom većina žena u period menopauze kada se događaju brojne biološke promjene u
organizmu.
Pokazane promjene koje se događaju ovisno o dobi i spolu i bolje poznavanje biološke varijabilnosti N-glikana
imunoglobulina A trebaju se uzeti u obzir u budućim istraživanjima potencijalnih prognostičkih, dijagnostičkih i
terapijskih biljega kao i biljega starenja.Changes in the N-glycosylation profile of immunoglobulin A have been proven to modify the function of the immune
system, as glycans participate in the protein folding and transport process, as well as in the intracellular and extracellular
signaling processes. Since N-glycosylation of immunoglobulin A has been unexplored so far, the aim of this study was
to 1) analyze the N-glycosylation of IgA in 84 healthy individuals, 2) investigate the behavior of individual glycan
structures depending on age and gender, and 3) identify glycan structures present on IgA that differ between women and
men in specific age groups. Glycan analysis included isolation of IgA from participants' plasma, deglycosylation of Nglycans, glycan labeling, purification and final separation of N-glycans using ultra-performance liquid chromatography
based on hydrophilic interactions (HILIC-UPLC).
The results showed greater changes in the levels of low-branched glycans compared to high-branched glycans (GP 23-
30), which level is more stable over time. Increased levels of agalactosylated glycans were observed in women with
increasing age. Monogalactosylated and digalactosylated glycans showed an increasing trend in women, while
digalactosylated glycans decreased in men with age. Glycan structures GP 8, 11, 16, and 21 exhibited statistically
significant differences between men and women in the third age group (50-60), which aligns with the graphical
representations of glycan trends. Therefore, we can conclude that the most significant changes in glycan levels,
particularly for the female gender, occur in the third age group (50-60), which may be associated with entering
menopause for most women when numerous biological changes occur in the body.
Shown results of changes depending on age and gender lead to a better understanding of the biological variability of Nglycans in immunoglobulin A, which should be taken into account for future research in identifying potential prognostic,
diagnostic, and therapeutic biomarkers, as well as biomarkers of aging
Towards the development of a biorelevant in vitro method for the prediction of nanoemulsion stability on the ocular surface
No full textOphthalmic oil-in-water nanoemulsions (NEs) are a complex technological platform, representing an advancement in the treatment of dry eye disease. In addition to enabling the incorporation of poorly soluble active pharmaceutical ingredients (APIs), NEs provide prolonged residence time of APIs and other formulation components and consequent replenishment and stabilization of the compromised tear film. Ophthalmic NEs have been on the market for over 20 years, but considering their complexity, as well as the complex nature of the ocular surface, they are still a poorly understood advanced dosage form. The objective of this study was to develop a biorelevant in vitro method that would be able to predict the behavior of ophthalmic NEs after application. With that goal, NE formulations differing in critical material attributes and critical formulation variables were employed and subjected to simulated tear turnover and blinking. By gradually increasing the complexity of the in vitro method, we were able to detect key parameters influencing NE stability. The undertaken study presents a step forward in the development of in vitro tools that are fundamental to the reliable, cost and time-effective development of innovative and generic topical ophthalmic NEs
Phytotherapy approach to the treatment of dyslipidemia with the aim of preventing cardiovascular diseases
No full textDislipidemija označava patološko stanje koje se manifestira kao neravnoteža koncentracije lipida,
odnosno povišene vrijednosti ukupnog i LDL-kolesterola te triglicerida i snižene vrijednosti HDLkolesterola.
Predstavlja jednog od glavnih čimbenika razvoja ateroskleroze i s njome povezanih
kardiovaskularnih bolesti. Poremećene koncentracije lipida čisti su primjer patološkog stanja
nastalog kako lošim prehrambenim navikama, tako i lošeg stila života. U svrhu pronalaska
potencijalnih fitopreparata za prevenciju i liječenje dislipidemije sa znanstveno potkrijepljenim
dokazima, pretraživane su baze podataka PubMed, Cochrane i ScienceDirect. Fitoterapeutici
proučavani u ovom diplomskom radu, crvena riža, češnjak, beta-glukani, artičoka, fitosteroli,
omega-3 masne kiseline, berberin, soja i polikozanol, kroz pregledana istraživanja pokazala su
pozitivne blagotvorne učinke na vrijednosti lipidnih parametara djelujući na više meta (inhibicija
sinteze, inhibicija apsorpcije i povećano izlučivanje kolesterola) uz minimalne nuspojave ukoliko se
primjenjuju sukladno preporukama. Osim na vrijednosti lipida, određeni fitoterapeutici pokazali su
pozitivne učinke na sam kardiovaskularni sustav. Trenutni podaci iz istraživanja ukazuju na
potencijalnu mogućnost primjene fitoterapeutika kao ključnog alata u poboljšanju koncentracija
lipida u plazmi kod ispitanika s blagom do umjerenom dislipidemijom uz niski kardiovaskularni
rizik, kao samostalni dodatak prehrani ili kao kombinacija sa standardnom farmakoterapijom te ih
je kao takve potrebno dodatno istraživati kroz dobro dizajnirana klinička ispitivanja.Dyslipidaemia is a pathological condition that manifests itself as an imbalance in the concentration
of lipids. It includes increased values of total and LDL-cholesterol and triglycerides and decreased
values of HDL-cholesterol. Dyslipidaemia is one of the main factors in the appearance of
atherosclerosis and cardiovascular diseases. Imbalance od lipid concentrations is an example of a
pathological condition caused by both bad nutrition habits and bad lifestyle. In order to find potential
phytopreparations for the prevention and treatment of dyslipidemia with scientifically supported
evidence were searched PubMed, Cochrane and ScienceDirect. The phytotherapeutics studied in this
thesis, red rice, garlic, beta-glucans, artichoke, phytosterols, omega-3 fatty acids, berberine, soy and
policosanol, through reviewed studies have shown positive beneficial effects on concetrations of
lipid parameters by affecting on multiple targets (synthesis inhibition, inhibition of absorption and
increased excretion of cholesterol) with minimal side effects if they are used according to
recommendations. In addition to lipid values, certain phytotherapeutics have also shown positive
effects on the cardiovascular system. Current research results indicate the potential possibility of
using phytotherapeutics as a key in improving plasma lipid concentrations in patients with mild to
moderate dyslipidemia with low cardiovascular risk, used as an independent dietary supplement or
in combination with standard pharmacotherapy. Also, there is a need for new researches of potential
phytotherapeutics through well-designed clinical trials
Uloga farmakogenomike i interakcija lijekova u varijabilnosti učinkovitosti i sigurnosti primjene direktnih oralnih antikoagulansa
No full textCilj istraživanja: Cilj ovog istraživanja je kritički osvrt na literaturne podatke koji se odnose
na utjecaj genskih varijanti na učinak i neželjene reakcije direktnih oralnih antikoagulacijskih
lijekova.
Materijali i metode: Za potrebe istraživanja i pisanja rada, od dostupnih baza podataka,
pretražene su baze podataka Medline i Pubmed prema ključnim riječima: direktni oralni
antikoagulansi (DOAK), dabigatran, rivaroksaban, apiksaban, edoksaban, farmakogenetika,
genski polimorfizmi CES1, CYP3A4, P-glikoprotein, MDR1/ABCB1, ABCB2. Odabrani
znanstveni članci obuhvaćaju sve dostupne članke iz područja farmakogenetike,
farmakogenomike DOAK-a u posljednjih 10 godina, uključujući originalne znanstvene članke
kao i pregledne radove koji zadovoljavaju tematiku rada. Također, u radu su prikazani
slučajevi iz kliničke prakse iz rutinskog testiranja u okviru obrade pacijenata u Kliničkom
bolničkom centru Zagreb u Odjelu za farmakogenomiku i individualizaciju terapije, uz
poštivanje svih etičkih načela.
Rezultati: Pregledom literature saznajemo da DOAK-i ovisno o metaboličkom putu stupaju u
interakcije sa određenim skupinama lijekova. Jednako tako, polimorfizmi prijenosnih
proteina i enzima utječu na pojavnost velikih štetnih događaja u vidu krvarenja.
Zaključak: Iako su novi oralni antikoagulansi sigurni lijekovi kod većine pacijenata, ipak
postoji određeni postotak pacijenata kod kojih je potrebna primjena s oprezom ovisno o
farmakogenetičkom profilu.Objectives: The aim of this study was to critically review the literature data related to the
influence of genetic variants on the effect and adverse reactions of direct oral
anticoagulants drugs.
Material and methods: For research and writing, from the available databases, Medline and
Pubmed databases were searched by keywords: direct oral anticoagulants (DOAC),
dabigatran, rivaroxaban, apixaban, edoxaban, pharmacogenetics, gene polymorphisms
CES1, CYP3A4, P-glycoprotein MDR1 / ABCB1, ABCB2. The selection of scientific articles in
the search included all available articles in the field of pharmacogenetics,
pharmacogenomics of DOAC in the last 10 years, including original scientific articles and
review papers that meet the topics and objectives of the research set in the paper. This
paper also included cases from routine testing within the treatment of patients at the
Clinical Hospital Center Zagreb in the Department of Pharmacogenomics and
Individualization of Therapy, in compliance with all ethical principles.
Results: A review of the literature reveals that DOAKs interact with certain groups of drugs
depending on their metabolic pathway. Likewise, polymorphisms of transport proteins and
enzymes affect the occurrence of major adverse events in the form of bleeding.
Conclusion: Although new oral anticoagulants are safe drugs in most patients, there is still a
certain percentage of patients who require caution depending on the pharmacogenetic
profile
Clinical and histological manifestations of drug-induced hepatotoxicity
No full textUnatoč pretkliničkim i kliničkim ispitivanjima, hepatotoksičnost predstavlja problem kod primjene mnogih postojećih
lijekova te ostaje najčešći uzrok povlačenja lijekova nakon stavljanja u promet.
U analiziranom razdoblju od siječnja 2019. do prosinca 2021. u KBC-u Zagreb nađen je 31 slučaj biopsijom potvrđenog
oštećenja jetrenog parenhima potencijalno uzrokovanog lijekovima; u 17 (54,84 %) žena i 14 (45,16 %) muškaraca.
Radilo se o 5 (16,13 %) pacijenata dječje dobi, 21 (67,74 %) pacijentu mlađe odrasle i odrasle dobi te o 5 (16,13 %)
pacijenata starije životne dobi. Kao najčešće kliničke manifestacije DILI-ja u ovom uzorku javljaju se nespecifična
jetrena lezija (12 pacijenata), abnormalni laboratorijski nalazi bez drugih kliničkih simptoma (8 pacijenata) te bilijarno
oštećenje, žutica i kolestaza (7 pacijenta). Laboratorijskim je pretragama najčešće nađeno miješano hepatocelularno i
bilijarno oštećenje, prisutno u 20 (64,52 %) pacijenata, slijedi hepatocelularno oštećenje u 10 (32,25 %) te bilijarno
oštećenje u jednog (3,23 %) pacijenta. U 10 (32,26 %) slučajeva radilo se o blagom, u 14 (45,16 %) o umjerenom, a u 7
(22,58 %) slučajeva o teškom oštećenju. Oštećenje se histološki najčešće manifestiralo steatozom, hemosiderozom te
steatohepatitisom, nađenima redom u 8, 7 i 6 slučajeva.
Lijekovi koji su potencijalno uzrokovali hepatotoksično oštećenje u više slučajeva su tamoksifen, prednizon,
amoksicilin-klavulanat, pembrolizumab i vinkristin, a pojedinačno nivolumab, metotreksat, azatioprin, didrogesteron,
valproat, izoniazid, aktinomicin D, ciklofosfamid, doksorubicin i paracetamol. Također su u više slučajeva nađeni
znakovi toksičnog djelovanja željeza kod pacijenata s višestrukim transfuzijama krvnih pripravaka u tijeku liječenja
hematoloških bolesti.Despite strict preclinical and clinical studies, drug-induced hepatotoxicity is a common problem during administration
of many drugs, and still remains the main reason for withdrawing drugs from the market.
This study evaluated liver biopsies with potential signs of drug induced liver injury (DILI), diagnosed in University
Hospital Centre Zagreb between January 2019 and December 2021. During the analyzed period, a 31 case of suspected
DILI was found: in 17 (54,84 %) females and 14 (45,16 %) males. There were 5 (16,13 %) pediatric patients and 26
(83,87 %) adults, including 5 older patients. Non-specific liver injury was the most common clinical diagnosis seen in
12 patients, abnormal liver tests without other symptoms were the main reason for biopsy in 8 patients, and biliary injury
with jaundice and cholestasis in 7 patients.
Mixed hepatocellular and biliary injury was the most common finding during laboratory work-up, seen in 20 (64,52 %)
cases, followed by hepatocellular injury in 10 (32,25 %) cases and biliary injury in a single (3,23 %) case. In 10 (32,26
%) cases injury was mild, in 14 (45,16 %) moderate, and in 7 (22,58 %) severe. The most common histological patterns
of injury were steatosis, hemosiderosis and steatohepatitis, seen in 8, 7 and 6 cases respectively.
Drugs suspected as a cause of DILI in multiple patients were tamoxifen, prednisone, amoxicillin-clavulanate,
pembrolizumab and vincristine. Nivolumab, methotrexate, azathioprine, dydrogesterone, valproic acid, isoniazid,
actinomycin D, cyclophosphamide, doxorubicin and paracetamol were suspected as a cause of DILI in one patient each.
Moreover, several patients showed signs of iron induced liver damage due to multiple blood transfusions during
chemotherapy treatment or after bone marrow transplantation
The influence of substituents on the nucleophilicity of purine bases
No full textKvantno-kemijskim metodama izračunate su kondenzirane Fukui funkcije za purin, adenin i derivate
adenina, te je provedena usporedba s prethodno poznatim eksperimentalnim rezultatima konjugacije
ferocenoil-klorida na purin i njegove derivate. SN2-slična supstitucijska reakcija između ferocenoilklorida i aniona adenina je regioselektivan proces u kojem omjer produkata (N7/N9-ferocenoil
izomera) ovisi o steričkim svojstvima supstituenta na N6-položaju. Veliki, razgranati supstituenti na
N6-atomu mogu ometati reakciju na N7-položaju, sprječavajući pristup elektrofila. Kao posljedica
toga, smanjuje se udio N7-produkta, tj. raste udio N9-ferocenoil regioizomera. U slučaju kad je
sterički učinak zanemariv, kao npr. kod purina, prevladava elektronski učinak N6-supstituenta, što
je potkrijepljeno izračunima kondenziranih Fukui funkcija. Svi izračuni pokazuju da je atom N7
nukleofilniji od N9-atoma u svim purinskim derivatima.Condensed Fukui functions for purine, adenine and adenine derivatives were calculated using
quantum chemical methods and a comparison was made with previously known experimental results
of ferrocenyl chloride conjugation to purine and its derivatives. The SN2-like substitution reaction
between ferrocenoyl chloride and adenine anion is a regioselective process in which the product
ratio (N7/N9-ferrocenoyl isomer) depends on the steric properties of the substituent at the N6-
position. Large, bulky substituents at the N6-atom can hinder the reaction at the N7-position,
preventing access of an electrophile. As a consequence, the proportion of N7-product decreases, i.e.
the proportion of N9-ferrocenoyl regioisomer increases. In the case when the steric effect is
negligible, such as for purines, the electronic effect of the N6-substituent prevails, which is
supported by calculations of condensed Fukui functions. All calculations show that the N7 atom is
more nucleophilic than the N9 atom in all purine derivatives
Biodiversity of mold in a damp dwelling
No full textStambeni prostori pogođeni vlagom pružaju idealne uvjete plijesnima za razmnožavanje. Povišena koncentracija određenih vrsta plijesni može uzrokovati ponajprije respiratorne simptome i bolesti u ljudi koji u tim prostorima provode duže vrijeme. Izolati plijesni iz zraka prikupljenih u stana pogođenog vlagom te iz vanjskog zraka (kontrolni uzorci) identificirani su do razine vrste na temelju molekularnog markera ITS za gljive te usporedbom nukleotidnih slijedova pojedinog izolata s podacima u javno dostupnim bazama podataka (NCBI, ISHAM). Veću bioraznolikost pokazali su izolati iz unutarnjeg prostora gdje su identificirane vrste: Aspergillus aureolatus (N=1), A. jensenii (N=1), A. purpureocrustaceus (N=11), A. sulphureoviridis (N=2), A. welwitschiae/A. niger (N=1), Cladosporium cycadicola (N=2), Penicillium robsamsonii (N=5), P. robsamsonii/P.hordei (N=1), P. rubens (N=1), P. speluncae (N=4), Stachybotrys limonispora/S. chartarum (N=1), Talaromyces wortmanii (N=1), Trametes versicolor (N=1) i Verruciconidia persicana (N=1). Vrste nađene samo u vanjskom zraku bile su Beauveria pseudobassiana (N=2) i Samsoniella hepiali (N=1), dok su vrste Ascochyta phacae (N=2), P. bialowiezense (N=5) i P. fimorum (N=10) identificirane u uzorcima unutarnjeg i vanjskog zraka. Dobiveni rezultati upućuju na razlike u identifikaciji obzirom na korištenu bazu podataka NCBI ili ISHAM te potrebu za ažuriranjem baze ISHAM nukleotidnim slijedovima novoopisanih vrsta roda Penicillium i Aspergillus. Upotreba sekundarnih molekularnih i/ili kemijskih markera omogućava preciznu identifikaciju plijesni do razine vrste zbog preklapanja u nukleotidnim slijedovima u regiji ITS među srodnim vrstama plijesni.Residential spaces affected by moisture provide ideal conditions for mold proliferation. Elevated concentrations of certain mold species can primarily cause respiratory symptoms and illnesses in individuals who spend extended periods of time in these areas. Mold isolates were recovered from indoor air sampled in moisture-affected homes and from outdoor air (control samples). Identification to the species level was conducted based on the ITS molecular marker for fungi by comparing nucleotide sequences of individual isolates with data in publicly available databases (NCBI, ISHAM). Greater biodiversity was observed among the indoor air isolates, and the following species were identified: Aspergillus aureolatus (N=1), A. jensenii (N=1), A. purpureocrustaceus (N=11), A. sulphureoviridis (N=2), A. welwitschiae/A. niger (N=1), Cladosporium cycadicola (N=2), Penicillium robsamsonii (N=5), P. robsamsonii/P.hordei (N=1), P. rubens (N=1), P. speluncae (N=4), Stachybotrys limonispora/S. chartarum (N=1), Talaromyces wortmanii (N=1), Trametes versicolor (N=1), and Verruciconidia persicana (N=1). The outdoor air isolates were identified to Beauveria pseudobassiana (N=2) and Samsoniella hepiali (N=1), while the species Ascochyta phacae (N=2), P. bialowiezense (N=5), and P. fimorum (N=10) were identified in both indoor and outdoor air samples. The results obtained indicate differences in identification depending on the NCBI or ISHAM database used and suggest updating the ISHAM database with nucleotide sequences of newly described species of the genus Penicillium and Aspergillus. The use of secondary molecular and/or chemical markers allows for precise mold identification at the species level due to overlap in nucleotide sequences in the ITS region among closely related mold species