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Antidepressant utilization in the Republic of Croatia from 2016 to 2020
No full textDepresija je jedan od najčešćih mentalnih poremećaja. Procjenjuje se da na globalnoj razini od depresije boluje preko 280 milijuna ljudi. Na razini Hrvatske prevalencija depresije iznosi oko 6,6 %. Depresija ne samo da smanjuje kvalitetu života i funkcionalnost pojedinca, već predstavlja i ekonomski teret za zdravstveni sustav. Obzirom na uređenost zdravstvenog sustava u Republici Hrvatskoj, pacijentima s postavljenom dijagnozom depresije na raspolaganju su antidepresivi s osnovne ili dopunske liste lijekova Hrvatskog zavoda za zdravstveno osiguranje.
U ovom je radu analizirano tržište antidepresiva u Hrvatskoj. Proučavan je broj registriranih lijekova, njihova cijena te potrošnja u razdoblju od 2016. do 2020. godine. U Hrvatskoj je u navedenom razdoblju bilo registrirano 18 molekula u različitim dozama. U 2016. na tržištu je bilo registrirano ukupno 98 različitih formulacija različitih proizvođača. Taj se broj do 2020. smanjio na 76.
Cijene jediničnih oblika lijekova varirale su. Najvišu je cijenu imala tableta od 25 mg agomelatina (8,97 kn), a najnižu tableta od 10 mg amitriptilina (0,33 kn).
Zaključeno je da je potrošnja antidepresiva rasla u analiziranom periodu. Najviše su propisivani selektivni inhibitori ponovne pohrane serotonina (sertralin i escitalopram), a najmanje triciklički antidepresivi. Obzirom na to da je financijski utrošak na terapiju antidepresivima godišnje iznosio 70-80 milijuna kuna, depresija predstavlja velik financijski teret za hrvatski zdravstveni sustav.Depression is one of the most common mental health issues. It is estimated that over 280 million people globally suffer from depression. The prevalence of depression in Croatia is around 6,6%. Depression does not only affect the quality of life and functionality of the patient but is also an economic burden for the health system. Considering the organization of the Croatian health system, all patients with diagnosed depression have access to antidepressants registered within Croatian Health Insurance Fund's registered drugs lists. This article analyses the antidepressants market in Croatia. The number of registered antidepressants, their price and consumption during the period from 2016 to 2020 have been studied. During the analyzed period 18 molecules were registered as antidepressants in different doses and forms in Croatia. In 2016 there were 98 different formulations registered by different brands. By 2020, the number of registered formulations was reduced to 76. Prices per pill varied during the analysis period. The highest price was noted for a 25 mg agomelatine pill (8,97 kn), and the lowest price was noted for a 10 mg amitriptyline pill (0,33 kn). It s concluded that the general consumption of antidepressants increased during the analysis period. Selective serotonin reuptake inhibitors (sertraline and escitalopram) were used most often, while tricyclic antidepressants were rarely used. Considering the fact that annually 70-80 million kunas is spent on depression therapy, depression presents a great financial burden for the Croatian health system
Utjecaj pandemije uzrokovane bolesti COVID-19 na adherenciju kroničnih pacijenata
No full textCilj: Svrha ovog istraživanja bila je ispitati adherenciju pacijenata s kroničnim bolestima te njihovo iskustvo i stavove vezane uz utjecaj pandemije COVID-19 na dostupnost zdravstvenih radnika, straha od zaraze u zdravstvenim ustanovama i utjecaja na adherenciju.
Ispitanici i metode: Ispitivanje je bilo dizajnirano kao presječno, opservacijsko. U ispitivanju je sudjelovalo 200 nasumično odabranih pacijenata diljem Hrvatske. Uključne kriterije su činili dob veća od 18 godina, dijagnoza barem jedne kronične bolesti, najmanje dva propisana lijeka na recept i da pacijent sam podiže svoje lijekove u ljekarni. Kriterije isključivanja činila su stanja u kojima pacijent nije u mogućnosti dati točne informacije, primjerice dijagnoza demencije. Sudjelovanje u istraživanju je bilo dobrovoljno, a pacijenti koji su zadovoljili kriterije za uključivanje, sami su ispunjavali upitnik. Upitnik je razvijen za potrebe ovog istraživanja, a sadržavao je podatke o socio-demografskim karakteristikama ispitanika, zatim dvije skale za procjenu adherencije (MAQ - Medication Adherence Questionnaire i MARS - Medication Adherence Report Scale© Prof. Rob Horne) te dio o utjecaju COVID-19 pandemije na uzimanje lijekova. Svi su podaci obrađeni statistički.
Rezultati: U ispitivanje je bilo uključeno 200 pacijenata, prosječne dobi 64,32 ± 13,04 godina. 44,5% ispitanika su bile osobe muškog, a 55,5% osobe ženskog spola. Svi ispitanici su imali dijagnozu barem jedne kronične bolesti, najčešće hipertenzije (71%). Ispitanici su u prosjeku imali 3,98 ± 1,68 dijagnoza te 6,40 ± 2,87 lijekova propisanih na recept. 57% ispitanika koristilo je barem jedan pripravak za samoliječenje. Rezultati dobiveni na MAQ i MARS skalama upućuju na visok stupanj adherencije među pacijentima (MAQ 2,45 ± 2,05; MARS 22,38 ± 2,64). Nisu pronađene statistički značajne razlike s obzirom na spol, dob, obrazovanje i bračni status. Pronađena je statistički značajna razlika adherencije prema mjestu stanovanja pri čemu su ispitanici koji žive u ruralnim područjima bili manje adherentni no oni u urbanim sredinama. S obzirom na dijagnozu, pronađena je statistički značajna razlika za pacijente koji boluju od astme i reumatoidnog artritisa (RA), pri čemu su se astmatičari pokazali manje adherentnima no ostali, a pacijenti s RA adherentnijima. Manji dio pacijenata je prestao s uzimanjem lijekova tijekom pandemije uzrokovane COVID-19 virusom, što se uglavnom odnosilo na pacijente s RA. 39% ispitanika izbjegavalo je zdravstvene ustanove zbog straha od zaraze, a 34% je imalo problema stupiti u kontakt s liječnikom obiteljske medicine.
Zaključak: Većina se pacijenata prilagodila promjenama do kojih je uslijed pandemije COVID-19 došlo u zdravstvenom sustavu te novonastala situacija nije značajnije utjecala na njihovu adherenciju. Ipak, pokazalo se da je više od trećine pacijenata imalo otežan pristup zdravstvenim ustanovama i liječnicima obiteljske medicine te bi trebalo poduzeti mjere kako bi u okolnostima epidemije zdravstvena skrb ostala jednako dostupna svim potrebitim osobama. Istraživanje je također ukazalo na skupine pacijenata pod povećanim rizikom od neadherencije; osobe koje boluje od astme su imale najnižu adherenciju, dok su osobe koje boluju od RA bile adherentnije od ostalih, ali najčešće ukinuli pojedine lijekove zbog straha od utjecaja COVID-19 bolesti.Objectives: The purpose of the study was to examine the adherence of patients with chronic diseases and their experience related to the impact of the COVID-19 pandemic on the availability of health workers, fear of infection in health facilities and the impact on adherence itself.
Patients and methods: The study was designed as a cross-sectional, observational study. The study involved 200 randomly selected patients throughout Croatia. Including criteria were age over 18, diagnosis of at least one chronic disease, at least two prescription drugs, and the patient picking up his or her own medication at the pharmacy. Exclusion criteria consisted of conditions in which the patient was unable to provide accurate information, such as a diagnosis of dementia. Participation in the study was voluntary, and patients who met the inclusion criteria completed the questionnaire themselves. The questionnaire was developed for the purposes of this research, and contained data on socio-demographic characteristics of respondents, then two scales for assessing adherence (MAQ - medication adherence questionnaire and MARS - Medication Adherence Report Scale © Prof. Rob Horne) and part on the impact of COVID- 19 pandemics on medication. All data were processed statistically.
Results: The study included 200 patients, mean age 64.32 ± 13.04 years. 44.5% of respondents were male and 55.5% female. All subjects were diagnosed with at least one chronic disease, most commonly hypertension (71%). Subjects had an average of 3.98 ± 1.68 diagnoses and 6,40 ± 2.87 prescription drugs. 57% of respondents used at least one self-medication drug. The results obtained on the MAQ and MARS scales indicate a high degree of adherence among patients (MAQ 2.45 ± 2.05; MARS 22.38 ± 2.64). No statistically significant differences were
found with respect to gender, age, education, and marital status. A statistically significant difference in adherence to place of residence was found, with respondents in rural areas being less adherent than those in urban areas. Based on the diagnosis, a statistically significant difference was found for patients with asthma and rheumatoid arthritis (RA), with asthmatics being less adherent and patients with RA being more adherent than others. A small proportion of patients stopped taking the medication during a pandemic caused by the COVID-19 virus, which mainly affected RA patients. 39% of respondents avoided health facilities for fear of infection, and 34% had trouble getting in touch with a physician.
Conclusion: Most patients have adapted to the changes that have taken place in the health care system as a result of the COVID-19 pandemic, and the new situation has not significantly affected their adherence. However, more than a third of patients have been shown to have difficulty accessing health facilities and family physicians, and measures should be taken to keep health care equally accessible to all those in need in the circumstances of the pandemic. The study also indicated groups of patients at increased risk of nonadherence; people with asthma had the lowest adherence, while people with RA were more adherent than others, but most often discontinued certain medications for fear of being affected by COVID-19 disease
Optimization of method for determination of transcripts of RNA and miRNA in exosomes from colorectal cancer patients
No full textKolorektalni karcinom (CRC) multifaktorska je bolest složene etiologije i visoke prevalencije. U većini slučajeva nastaje iz na početku benignih adenoma koji postaju maligni nakon niza genskih mutacija u epitelnim stanicama kolona. Karakterizira ga spor razvoj i duga presimptomatska faza što predstavlja mogućnost za njegovo rano otkrivanje i liječenje. Tekuća biopsija neinvazivna je metoda za određivanje molekularnog profila tumora uključujući CRC, a egzosomalne RNA i miRNA obećavajući su biomarkeri za dijagnozu, prognozu i evaluaciju odgovora na terapiju u CRC-u. Cilj ovog rada bila je optimizacija metode za određivanje transkripata RNA i miRNA u egzosomima pacijenata sa CRC-om koji su u literaturi istaknuti kao potencijalni prognostički i terapijski biljezi ove bolesti. RNA je izolirana iz egzosoma iz plazme 18 bolesnika s potvrđenim CRC-om. Ekspresija C-MYC te referentnih gena B2M, PPIA i GAPDH, određena je pomoću qPCR tehnike i TaqMan eseja, a ekspresija miR-19a-3p, miR-92a-3p, miR-125-3p, miR-193a-3p, miR-210-3p te referentnih mir-103a-3p, mir 1228-3p i miR-520d-3p pomoću SYBR green tehnologije. Koncentracija RNA kretala se u rasponu od 2,44-51,20 ng/ μl sa medijanom od 11,48 ng/μl. Gen C-MYC kao i ispitivani referentni geni nisu dokazani niti u jednom uzorku što može značiti da su te mRNA prevelike za pakiranje u egzosome. S druge strane, od predloženih referentnih miRNA dokazana je ekspresija jedino miR-103a-3p zbog čega je kao standard s kojim se uspoređivala ekspresija ciljnih miRNA korištena sintetička UniSp6. U najvećem broju uzoraka (svih 18) dokazane su miR-19a-3p i miR-92a-3p dok je u najmanjem broju uzoraka (3) dokazana miR-125-3p. Iz dobivenih rezultata može se zaključiti da su uzorci unatoč niskim koncentracijama RNA dovoljno kvalitetni za određivanje većine miRNA od interesa u našem istraživanju ali ne i za mRNA.Colorectal cancer (CRC) is multifactorial disease with complex etiology and high prevalence among population. In most cases it arises from initially benign adenomas that become malignant after series of gene mutations in colon epithelial cells. It is characterized by slow development and long presymptomatic phase which gives opportunities for early detection and treatment. Liquid biopsy is non-invasive method for determination of cancer molecular profile including CRC, while exosomal RNAs and miRNAs are promising biomarkers for diagnosis, prognosis, and evaluation of therapy response in CRC patients. The goal of this research was to optimize the method for assessment of RNA and miRNA isolated from exosomes of CRC patients found to be promising potential prognostic and therapeutic markers of this disease. RNA was isolated from exosomes from plasma of 18 patients diagnosed with CRC. Expression of C-MYC and reference B2M, PPIA and GAPDH genes was determined using qPCR and TaqMan assays, and expression of miR-19a-3p, miR-92a-3p, miR-125-3p, miR-193a-3p, miR-210-3p and three reference miRNAs: mir-103a-3p, mir 1228-3p and miR-520d-3p was determined using SYBR green technology. Concentration of RNA ranged from 2,44 ng/μl to 51,20 ng/μl with median of 11,48 ng/μl. C-MYC gene and three reference genes weren’t detected in any sample what can imply that these mRNAs are too big for packing in exosomes. On the other hand, only miR-103a-3p was detected of three potential reference genes, which is why UniSp6 was used as standard to normalise expression of target miRNAs. MiR-19a-3p and miR-92-a-3p were detected in most samples (18) while miR-125-3p was detected in lowest number of samples (3). We can conclude that despite low concentrations, our samples have sufficient quality for determination of the expression of most of the targeted miRNAs in this research, but the same cannot be said for mRNAs
Ultrasound isolation of antioxidants from olive pomace and development of highly valued nutraceutical
No full textProizvodnjom maslinovog ulja zaostaju velike količine nusproizvoda koji se smatraju otpadom, a zbog
kompleksnosti sastava i dokazane toksičnosti velika su opasnost za okoliš. Komina masline, jedan od glavnih
nusprodukata proizvodnje maslinovog ulja, značajan je izvor prirodnih antioksidansa, od kojih su najznačajniji
tirosol, hidroksitirosol i oleuropein. Uzevši u obzir njihove brojne pozitivne učinke na zdravlje, osnovni cilj ovog
istraživanja bio je razvoj zelenog postupka dobivanja suhog ekstrakta komine masline bogatog hidroksitirosolom,
tirosolom i oleuropeinom primjenom kombinacije ultrazvučne ekstrakcije i uklapanja u ciklodekstrine. S ciljem
utvrđivanja potencijala daljnje primjene dobivenih ekstrakata bila je nužna njihova funkcionalna karakterizacija. U
prvoj fazi istraživanja optimirani su postupci klasične ekstrakcije, inovativne ultrazvučne ekstrakcije i ultrazvučne
ekstrakcije uz dodatak ciklodekstrina. Zatim je u drugom dijelu istraživanja ispitana primjenjivost postupka
liofilizacije te utjecaj korištenih ciklodekstrina na tehnološke i kemijske karakteristike suhog ekstrakta. U završnoj
fazi istraživanja provedena je funkcionalna karakterizacija suhog ekstrakta komine masline u naprednim biološkimi
model sustavima hrane te je određena bioraspoloživost glavnih aktivnih polifenolnih sastavnica. Optimiranom
klasičnom ekstrakcijom dobiveni su ekstrakti s oleuropeinom kao najzastupljenijim fenolnim spojem (115,14±0,19
mg/kg svježe komine masline). Primjenom optimalnih uvjeta ultrazvučne ekstrakcije u kombinaciji s uklapanjem u
ciklodekstrine, postignuti su još veći prinosi oleuropeina (1744 mg/kg komine masline), tirosola (1117 mg/kg komine
masline) i hidroksitirosola (887 mg/kg). Uklapanje u cikodekstrine imalo je pozitivan utjecaj na kemijski sastav i
antioksidativnu aktivnost dobivenih ekstrakata. Ekstrakti s dodatkom hidroksipropil-β-ciklodekstrina i nasumično
metiliranog β-ciklodekstrina pokazali su osobitu antioksidativnu aktivnost, pa su tako u emulzijskom modelu imali
značajno višu antioksidativnu aktivnost (1242 mg/g i 1422 mg/g Trolox ekvivalentna) od Troloxa kao referentnog
antioksidansa. U ostalim su modelima (primjenjeni u koncentracijskim nivoima 2-3%) pružili antioksidativnu zaštitu
usporedivu s često korištenim sintetskim antioksidansima. Rezultati dobiveni primjenom gastrointestinalnog modela
pokazuju visoku biodostupnost polifenola komine masline, a dodatkom ciklodekstrina dodatno je poboljšana
gastrointestinalna stabilnost tirosola.Olive oil production generates large quantities of by-products, which are considered waste and pose a major threat
to the environment due to their complex composition and proven toxicity. Olive pomace, one of the main by-products
of olive oil production, is a significant source of natural antioxidants, the most important of which are tyrosol,
hydroxytyrosol and oleuropein. Due to its numerous beneficial effects on health, the main objective of this study was
developing an environmentally friendly process of production of the olive pomace dry extract rich in hydroxytyrosol,
tyrosol and oleuropein using a combination of ultrasonic extraction and cyclodextrin encapsulation. Functional
characterization of the extracts obtained was necessary to determine their further application potential. In the first
phase of the research, the methods of classical extraction, innovative ultrasonic extraction and ultrasonic extraction
combined with cyclodextrin encapsulation were optimized. In the second part of the research, the applicability of the
freeze-drying process and the influence of cyclodextrins on the technological and chemical properties of the dry
extracts were studied. In the last phase of the research, the functional characterization of olive pomace dry extracts
in advanced biological and food model systems was performed and the bioavailability of the main active polyphenolic
components was determined. Optimized classical extraction yielded extracts with oleuropein as the most abundant
phenolic compound (115.14 ± 0.19 mg/kg fresh olive pomace). By applying optimal ultrasonic extraction conditions
in combination with cyclodextrin encapsulation, even higher yields of oleuropein (1744 mg/kg olive pomace), tyrosol
(1117 mg/kg olive pomace), and hydroxytyrosol (887 mg/kg) were obtained. Encapsulation with cyclodextrin had a
positive effect on the chemical composition and antioxidant activity of the extracts obtained. Among the
cyclodextrins studied, the extracts encapsulated with hydroxypropyl-β-cyclodextrin and random methylated-β-
cyclodextrin showed particularly good antioxidant activity and were especially effective in emulsion systems (1242
mg/g and 1422 mg/g Trolox equivalent, respectively), exhibiting significantly higher antioxidant activity than Trolox
(reference antioxidant). In other models, they provided antioxidant protection comparable to commonly used
synthetic antioxidants at concentrations of 2-3%. The results of the gastrointestinal model showed high bioavailability
of olive pomace polyphenols, and the addition of cyclodextrins further improved the gastrointestinal stability of
tyrosol
Influence of the inlet temperature on the properties of the spray-dried donepezil-loaded microspheres
No full textMetoda sušenja raspršivanjem pogodna je za pripravu praškastih sustava za nazalnu primjenu zbog mogućnosti optimizacije procesnih i formulacijskih parametara te priprave produkta željenih svojstava. Zbog svojih prednosti, nazalni put primjene lijekova sve se više istražuje te se potiču daljnja istraživanja kritičnih atributa kvalitete nazalnih formulacija lijeka kako bi se osigurala optimalna primjena i učinkovitost.
Cilj ovog diplomskog rada bio je pripraviti mikrosfere s donepezilom za nazalnu primjenu metodom sušenja raspršivanjem te ispitati ovisnost fizičko-kemijskih svojstava mikrosfera o ulaznoj temperaturi u proizvodnom procesu. Mikrosfere s donepezilom uspješno su pripravljene sušenjem raspršivanjem otopine donepezila (0,4 %, m/V), manitola (6,0 %, m/V) i kitozana (1,5 %, m/V) pri ulaznoj temperaturi od 110, 125, 140 i 155 °C, snazi sapnice od 65 %, radu aspiratora od 100 %, radu pumpe od 10 % te protoku zraka od 35 %. Iskorištenje procesa iznosilo je 54,5 – 66,0 %. Postignuta je visoka uspješnost uklapanja donepezila u rasponu 97,5 ± 2,6 – 99,4 ± 2,0 % te je sadržaj lijeka (4,94 ± 0,13 – 5,03 ± 0,10 %) bio blizu teorijske vrijednosti (5,06 %). Volumni promjeri Dv10, Dv50 i Dv90 bili su redom u rasponima 7,3 ± 0,5 – 9,9 ± 1,4 μm, 26,3 ± 0,9 – 35,7 ± 1,6 μm i 60,3 ± 0,7 – 72,7 ± 1,1 μm. Povećanje ulazne temperature zraka za sušenje rezultiralo je povećanjem iskorištenja procesa (do 140 °C), smanjenjem veličine mikrosfera s donepezilom i poboljšanjem svojstava tečenja. Za sve pripravljene mikrosfere s donepezilom i neovisno o ulaznoj temperaturi u procesu sušenja, kut raspršenja (17,5 ± 1,7 – 19,2 ± 0,2 º) i ostatak mikrosfera u kapsuli nakon raspršivanja (0,0 ± 0,0 – 2,0 ± 0,7 % nominalne doze) pokazuju potencijal za učinkovitu dostavu adekvatne doze donepezila u nosnu šupljinu.Spray drying presents a suitable method for the preparation of nasal powder formulations offering the possibility of optimizing process and formulation parameters to gain the product with desired properties. Nasal route of drug delivery is being increasingly investigated due to its recognized advantages, thus further research of critical quality attributes of nasal drug formulations is encouraged to ensure optimal drug administration and efficacy.
The aim of this study was to prepare spray-dried microspheres for nasal donepezil delivery and to investigate the influence of inlet air temperature in the production process on the physico-chemical properties of the microspheres. Donepezil-loaded microspheres were successfully prepared by spray drying of a donepezil (0.4%, m/V), mannitol (6.0%, m/V) and chitosan (1.5%, m/V) solution at inlet temperature of 110, 125, 140 and 155 °C, nozzle power of 65 %, aspirator rate of 100 %, pump rate of 10 % and air flow of 35 %. The process yield ranged between 54.5 and 66.0 %. Drug entrapment efficiency was high (97.5 ± 2.6 – 99.4 ± 2.0 %) and drug loading (4.94 ± 0.13 – 5.03 ± 0.10 %) was close to the theoretical value (5.06 %). Volume diameters Dv10, Dv50 and Dv90 ranged from 7.3 ± 0.5 to 9.9 ± 1.4 μm, 26.3 ± 0.9 to 35.7 ± 1.6 μm and 60.3 ± 0.7 to 72.7 ± 1.1 μm, respectively. Increase of the inlet air temperature resulted with an increase in process yield (up to 140 °C), a reduction in size distribution of donepezil-loaded microspheres and an improvement of flow properties. For all donepezil-loaded microspheres, regardless of inlet-air temperature in the production process, spray cone angle (17.5 ± 1.7 – 19.2 ± 0.2 º) and percentage of microspheres retained within the capsule upon aerosolization (0.0 ± 0.0 – 2.0 ± 0.7 % of the nominal dose) indicate the potential for effective delivery of adequate donepezil dose to the nasal cavity
Evaluation of serum markers in diagnosis of hepatocellular carcinoma in liver cirrhosis of alcohol etiology
No full textHepatocelularni karcinom (HCC) je epitelna zloćudna novotvorina s prisutnom hepatocelularnom diferencijacijom
i najčešća je primarna zloćudna novotvorina jetre. Ciroza jetre je najznačajni rizični čimbenik za razvoj HCC-a.
Dosadašnja istraživanja pokazuju da će 1/3 bolesnika s cirozom razviti i HCC, a oko 90% bolesnika s HCC-om
ima i cirozu jetre. S obzirom da je ciroza ključan rizični čimbenik u nastanku HCC-a, a etilogija ciroze ima ulogu
u mehanizmima kancerogeneze, temeljni cilj ovog istraživanja bio je ispitati individualnu i kombiniranu
dijagnostičku točnost alfa-fetoproteina (AFP), lens culinaris aglutinin A-reaktivne frakcije alfa-fetoproteina (AFPL3),
des-gama-karboksi protrombina (PIVKAII), glipikana 3 (GP3), antigena pločastih stanica karcinoma-1
(SCCA1), cistatina B (CSTB) i hepatocitnog faktora rasta (HGF) kao potencijalnih tumorskih biljega za dijagnozu
HCC-a kod bolesnika s alkoholnom cirozom jetre. Radiološke slikovne metode i/ili tkivno uzorkovanje (biopsija
tumora) korišteni su kao "zlatni dijagnostički standard" u dijagnozi HCC-a.
Ispitivanje je provedeno kod 31 bolesnika s alkoholnom cirozom bez HCC-a i 32 bolesnika s alkoholnom cirozom
sa HCC-om. U ispitivanje je uključeno i 20 zdravih ispitanika kako bi se verificirale granične vrijednosti za one
biljege za koje ne postoji specifikacija proizvođača. Prvo uzorkovanje periferne venske krvi provedeno je u stanju
gladovanja, a drugo nakon urađenih slikovnih pretraga i prije bilo kakvih terapijskih intervencija. Biopsija tumora
je rađena nakon uzorkovanja, ukoliko je bila indicirana.
Koncentracije PIVKAII i AFP-a, bile su značajno više u bolesnika s alkoholnom cirozom i HCC-om nego u
bolesnika s alkoholnom cirozom bez HCC-a, dok su pojedinačne dijagnostičke izvedbe ostalih ispitivanih biljega
bile nedostatne.
"Najbolja" kombinacija tumorskih biljega uključuje AFP i PIVKAII s dijagnostičkom točnosti od 97,4%. Također,
koncentracija AFP –a pokazala je diskriminativnu sposobnost za razlikovanje kurabilnog od inkurabilnog stadija
bolesti (s obzrom na veličinu i broj tumora), što je potrebno potvrditi daljnjim istraživanjima.
Među ostalim provedenim testovima, koncentracija hemoglobina, broj trombocita, aktivnosti alaninaminotransferaze
(ALT) i gama-glutamil-transferaze (GGT) te koncentracije amonijaka i feritina bile su značajno
više u bolesnika s HCC-om i alkohonom cirozom u odnosu na bolesnike s alkoholnom cirozom bez HCC-a.
Dodatno, serumske koncentracije CSTB i SCCA1 pokazale su dobru pozitivnu povezanost s funkcionalnim
stadijem ciroze.
Rezultati ovog istraživanja upućuju na zaključak da AFP i PIVKAII imaju najbolju diskriminativnu sposobnost za
dijagnozu HCC-a u bolesnika s alkoholnom cirozom jetre, uz dodatno poboljšanje dijagnostičke točnosti ukoliko
se koriste u kombinaciji. U usporedbi s ranijim istraživanjima, može se pretpostaviti da bi dijagnostička izvedba
tumorskih biljega mogla ovisiti o etiologiji bolesti jetre u podlozi HCC-a, za što su potrebna daljnja istraživanja.Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Approximately 90 % of HCC
cases are diagnosed in patients with pre-existing cirrhotic liver. Since cirrhosis is a key risk factor in the
development of HCC, and the etiology of cirrhosis plays a role in the mechanisms of carcinogenesis, the basic
goal of this study was to examine the individual and combined diagnostic accuracy of alpha-fetoprotein (AFP),
lens culinaris agglutinin (LCA) reactive fration of AFP (AFP-L3), protein induced by vitamin K absence or
antagonist-II (PIVKAII), glypican-3 (GP3), squamous cell carcinoma antigen 1 (SCCA1), cystatin B (CSTB) and
hepatocyte growth factor (HGF) as potential tumor markers for the diagnosis of HCC in patients with alcoholic
liver cirrhosis(ALC) using imaging techniques and/or tumor biopsy as reference standard in the diagosis of HCC.
The study was performed in 31 patients with ALC and 32 patients with ALC and HCC. 20 healthy subjects were
also included in order to verify cut-off values. The first sampling of peripheral venous blood was performed in the
fasting state, and the second after imaging tests and before any therapeutic interventions. Tumor biopsy was
performed after second sampling, if it was indicated.
Serum concentrations of AFP and PIVKAII were significantly higher in patients with ALC and HCC than in
patients with ALC, while individual diagnostic performance of the other markers was inadequate.
The “best” combination of tumor markers includes AFP and PIVKAII with diagnostic accuracy of 97,4%.
The concentration of AFP showed a discriminant ability to distinguish curable from incurable stage of the disease
(given the size and number of tumors), which needs to be confirmed by further research.
Among other performed tests, hemoglobin concentration, platelet count, alanine aminotransferase (ALT) and
gamma-glutamyl transferase (GGT) activities, and ammonia and ferritin concentrations were significantly higher
in patients with HCC and ALC than in patients with ALC.
Additionally, serum concentrations of CSTB and SCCA1 showed a good positive correlation with the functional
stage of cirrhosis.
The results of this study suggest that AFP and PIVKAII have the best discriminant ability to diagnose HCC in
patients with alcoholic liver cirrhosis, with a further improvement in diagnostic accuracy when used in
combination. Compared to previous studies, it can be assumed that the diagnostic performance of tumor markers
could depend on the etiology of HCC-based liver disease and further research is needed to confirm this
Role of extracellular adenosine-triphosphate and heat shock protein 70 in chronic obstructive pulmonary disease
No full textKronična opstrukcijska plućna bolest je treći vodeći uzrok smrtnosti u svijetu i time predstavlja veliki izazov moderne
medicine. Svjetska zdravstvena organizacija pretpostavlja značajan porast broja oboljelih u budućnosti zbog povećane
prisutnosti rizičnih čimbenika, od kojih su najznačajniji aktivno i pasivno pušenje te onečišćenje zraka. Unatoč velikoj
prevalenciji, dijagnostika i liječenje su još uvijek nedostatni. Velik broj oboljelih nema postavljenu dijagnozu, dijelom
zbog nedovoljne edukacije samog pacijenta koji simptome ne prepoznaje, a dijelom zbog nedovoljnih dijagnostičkih
metoda. Liječenje može smanjiti simptome i spriječiti buduće egzacerbacije, ali ne može dovesti do izlječenja.
Pacijenti koji boluju od KOPB-a imaju značajno narušenu kvalitetu života, a troškovi liječenja predstavljaju problem i
pacijentima i zdravstvenom sustavu. Kako bi se omogućila pravovremena dijagnostika i postigli bolji ishodi liječenja,
potrebno je identificirati i razjasniti patofiziološke mehanizme bolesti koji su trenutno kompleksni i nepoznati.
Cilj ovog diplomskog rada je napraviti pregled dostupnih podataka o KOPB-u te izvanstaničnom ATP-u i
izvanstaničnom Hsp70 kao potencijalnim biomarkerima. eATP i eHsp70 su molekule koje, kad se nalaze izvan
stanice, djeluju kao molekulski obrasci povezani s oštećenjem. Imaju važnu ulogu u upalnim procesima kod različitih
bolesti, pa tako i KOPB-a, a dosadašnja istraživanja potvrđuju njihovu povezanost s KOPB-om. Zabilježene su njihove
povećane koncentracije u pacijenata s KOPB-om u usporedbi sa zdravim ispitanicima. Daljnja istraživanja mogla bi
potvrditi njihovu ulogu kao potencijalnih biomarkera koji omogućuju raniju dijagnozu bolesti i olakšavaju
klasifikaciju pacijenata prema GOLD smjernicama. Saznanja o njihovom točnom djelovanju i signalnim putovima
mogla bi dovesti do razvoja novih dijagnostičkih metoda ili otkrivanja novih terapijskih meta, a time i do uspješnijeg
liječenja i smanjenja mortaliteta.Chronic obstructive pulmonary disease is the third leading cause of death in the world and thus represents a major
challenge for modern medicine. The World Health Organization assumes a significant increase in the number of patients
in the future due to the increased presence of risk factors, the most significant of which are active and passive smoking
and air pollution. Despite the high prevalence, diagnosis and treatment are still insufficient. A large number of patients
have not been diagnosed, partly due to insufficient education of the patients who do not recognize the symptoms, and
partly due to insufficient diagnostic methods. Treatment can reduce symptoms and prevent future exacerbations, but it
cannot cure the disease. Patients suffering from COPD have a significantly impaired quality of life, and the cost of
treatment is a problem for both patients and the health care system. In order to enable timely diagnosis and achieve better
treatment outcomes, it is necessary to identify and clarify the pathophysiological mechanisms of the disease that are
currently complex and unknown.
The aim of this thesis is to review the available data on COPD and extracellular ATP as well as extracellular Hsp70 as
potential biomarkers. eATP and eHsp70 are molecules that, when present outside the cell, act as danger-associated
molecular patterns. They play an important role in inflammatory processes in various diseases, including COPD, and
previous research confirms their association with COPD. Increased concentrations have been reported in patients with
COPD compared to healthy subjects. Further research could confirm their role as potential biomarkers that enable earlier
diagnosis of the disease and facilitate the classification of patients according to the GOLD guidelines. Knowledge of
their exact action and signalling pathways could lead to the development of new diagnostic methods or the discovery of
new therapeutic targets, and thus to more successful treatment and reduced mortality
Psihičke nuspojave statina
No full textCilj istraživanja: Utvrditi sigurnost primjene statina, posebice iz razloga što se oni široko primjenjuju u općoj populaciji, a mogu imati neželjene nuspojave koje narušavaju kvalitetu života.
Materijal: Pregledana je znanstvena i stručna literatura, publikacije stručnih udruga i institucija te drugih raspoloživih izvora.
Rezultati: Statini se često dovode u vezu sa ozbiljnim psihičkim nuspojavama kao što su: oštećenje kognitivnih funkcija, razvoj demencije i depresije te agresivnog ponašanja. Postoje istraživanja koji podupiru ove tvrdnje, ali isto tako, postoje i istraživanja koja su dala suprotne rezultate. Najviše kognitivnih nuspojava prijavljeno je za atorvastatin i simvastatin, što je vjerojatno posljedica njihove lipofilnosti i mogućnosti prolaska kroz krvno-moždanu barijeru. Kod osoba sa Alzheimerovom demencijom i normalnom razinom kolesterola, liječenje simvastatinom nije imalo utjecaj na pogoršanje simptoma bolesti. Samo se simvastatin može granično povezati sa povećanjem depresivnih simptoma, iako je kvaliteta dokaza koji tome idu u prilog niska. U mnogim studijama je istaknuto da su u osoba sa agresivnim poremećajima ponašanja te u onih pojedinaca koji su pokušali suicid, pronađene niske serumske koncentracije kolesterola.
Zaključak: Postoje oprečni rezultati istraživanja utjecaja statina na kognitivnu funkciju. Statini ne odgađaju kognitivno pogoršanje kod pacijenata sa poznatom demencijom. Psihijatrijski učinci povezani sa statinima rijetki su i ne sprečavaju moguće događaje koji će se najvjerojatnije dogoditi u osjetljivih bolesnika sa subkliničkim oštećenjem neurotransmiternih puteva. Pretpostavke nisu bile potvrđene u većini studija koje su trebale istražiti određene psihičke nuspojave. Potencijalne limititacije ovih studija predstavljaju varijabilnost kriterija koji su usvojeni za mjerenje krajnjih točaka, temeljenih na velikom broju različitih parametara i upitnika za procjenu neuropsihijatrijskih poremećaja. Neki od ovih alata možda nisu odgovarajući za identificiranje takvih događaja. Većina uključenih studija provedene su na malim populacijama i nisu mogle imati dovoljno snage za procijeniti rizik od takvih rijetkih događaja.Objectives: The aim of this paper is to determine the safety of statin therapy because it is widely used in the general population, and may have side effects that impair quality of life.
Material: For this purpose, relevant scientific and professional literature, publications of professional institutions and other available sources were reviewed.
Results: Statins are often associated with serious psychological side effects such as: impaired cognitive function, development of dementia and depression, aggressive behavior. There are studies that support these claims, but also, there are studies that have given the opposite results. Most cognitive side effects have been reported with atorvastatin and simvastatin, probably due to their lipophilicity and ability to cross the blood-brain barrier. In people with Alzheimer's dementia and normal cholesterol levels, simvastatin treatment had no effect on worsening the symptoms of the disease. Only simvastatin may be marginally associated with an increase in depressive symptoms, although the quality of the evidence to support this is low. Many studies have shown that low serum cholesterol levels have been found in people with aggressive behavioral disorders and in those individuals who have attempted suicide.
Conclusion: There are conflicting research results on the effect of statins on cognitive function. Statins do not delay cognitive deterioration in patients with known dementia. Psychiatric effects associated with statins are rare and do not prevent possible events that are most likely to occur in susceptible patients with subclinical neurotransmitter pathway impairment. Assumptions were not confirmed in most studies that were to investigate certain psychological side effects. The potential limitations of these studies represent the variability of the criteria adopted to measure endpoints, based on a large number of different parameters and questionnaires for the assessment of neuropsychiatric disorders. Some of these tools may not be appropriate for identifying that events. Most of the studies involved were conducted on small populations and could not have enough strength to assess the risk of such rare events
Utjecaj topikalne primjene vitamina C na proces starenja kože
No full textCilj istraživanja
Na tržištu se nalazi veliki broj različitih lokalnih pripravaka s različitim oblicima i dozama vitamina C koji se koriste za usporavanje procesa starenja kože lica. Cilj specijalističkog rada je pregled znanstvenih studija u kojima je ispitivano topikalno djelovanje vitamina C na proces starenja kože lica kako bi se napravila sistematizacija rezultata provedenih istraživanja.
Materijal / Ispitanici i metode
Za potrebe pisanja ovog specijalističkog rada je pretražena elektronička baza podataka PubMed. Pretraživanjem su obuhvaćene znanstvene studije koje su ispitivale topikalno djelovanje vitamina C na proces starenja kože. Uključene su i studije koje su ispitivale različite kombinacije vitamina C s brojnim sintetskim, ali i prirodnim djelatnim tvarima. Odabir znanstvenih studija je bio ograničen na kliničke studije objavljene na engleskom jeziku. Pregledane su sve one koje imaju dostupne cjelovite tekstove ili iznimno samo sažetke.
Rezultati
Obrađene su ukupno 23 studije koje su ispitivale učinkovitost topikalnog vitamina C na proces starenja kože. Pretražene studije su dokazale djelotvoran učinak vitamina C u biosintezi kolagena, povećanju gustoće kožnih papila, povećanju elastičnosti i kao antioksidansa. Nekoliko studija je pokazalo dobru podnošljivost tretmana. Inovativne formulacije vitamina C s različitim sustavima dostave pokazale su se dobre u rješavanju problema stabilnosti. Kombinacije vitamina C s drugim tvarima doprinijele su postizanju bolje učinkovitosti.
Zaključak
Topikalni pripravci s vitaminom C su pokazali značajno djelovanje u procesu starenja kože. Dodatak drugih aktivnih tvari kao i inovativni farmaceutski oblici mogu osigurati stabilnost vitamina C uz očuvanje učinkovitosti. Unatoč tomu, potrebna su dodatna ispitivanja uz dugoročno praćenje pacijenata i nakon prestanka upotrebe terapije, što će pridonijeti boljem uvidu u učinkovitost i sigurnost topikalne primjene vitamina C.Objectives
There is a large number of different topical preparations on the market with different forms and doses of vitamin C that are used to slow down the aging process of facial skin. The aim of the specialist work is to review scientific studies in which the topical effect of vitamin C on the aging process of facial skin was examined in order to systematize the results of research.
Material/Patients and Methods
For the purpose of writing this specialist paper, the electronic database PubMed was searched. The search included scientific studies that examined the topical effects of vitamin C on the aging process of the skin. The studies that have examined different combinations of vitamin C with a number of synthetic as well as natural active ingredients were also included. The selection of scientific studies was limited to clinical studies published in English. All of those studies that had full texts available or exceptionally only abstracts were reviewed.
Results
A total of 23 studies examining the effectiveness of topical vitamin C on the skin aging process were examined. These studies have proven the effective effect of vitamin C in collagen biosynthesis, increasing the density of skin papillae, as an antioxidant and increasing elasticity. Several studies have shown a good tolerability of treatment. Innovative vitamin C formulations with different delivery systems have proven to be good at solving stability problems. Combinations of vitamin C with other substances have contributed to achieving better efficacy.
Conclusion
Topical preparations with vitamin C have shown significant effects in the aging process of the skin. The addition of other active substances as well as innovative pharmaceutical forms can ensure the stability of vitamin C while maintaining efficacy. Nevertheless, additional studies are needed in addition to long-term monitoring of patients after discontinuation of therapy, which will contribute to better insight into the efficacy and safety of topical vitamin C administration
Resistance of linen canvas mycobiota to gamma irradiation
No full textVeliki dio kulturne baštine čine predmeti od organskog, biljnog materijala, platna. Kao takvi izrazito su podložni kontaminaciji gljivicama koje svojim djelovanjem ubrzavaju njegovo propadanje. Jedna od najpogodnijih metoda za zaustavljanje destruktivnog djelovanja gljivica je gama zračenje. U ovom radu ispitivana je otpornost mikobiote lanenog platna na gama zračenje, te otpornost inokuliranog sekundarnog kolonizatora, vrste Cladosporium sphaerospermum. Uzorci su tretirani pomoću izvora u Laboratoriju za radijacijsku kemiju i dozimetriju (LRKD) Instituta Ruđer Bošković (IRB). Primijenjene su apsorpcijske doze od 2, 7, 20 i 50 kGy u dvije brzine zračenja 0,1 Gy/s i 8,6 Gy/s. Mikrobiološka analiza ozračenih uzoraka provedena je neposredno nakon zračenja te 14., 28., i 56. dan nakon zračenja.
Prirodnu mikobiotu platna čine vrste iz rodova Penicillium, Cladosporium, Fusarium i kvasci. Antifungalni učinak gama zračenja ovisan je o dozi i brzini doze. Vrste Fusarium spp., narančasti kvasci i Cladosporium spp. pokazali su se najrezistentnijim gljivicama na gama zračenje. Iz rezultata pokusa određena je i D10 vrijednost od 13,72 kGy za višu brzinu zračenja (8,6 Gy/s). Potrebno je provesti kemijsku analizu platna kako bi se dobio bolji uvid u utjecaj određenih doza i brzina zračenja na sastav platna. Za učinkovitu primjenu gama zračenja u konzervaciji platnenih predmeta kulturne baštine potreban je interdisciplinarni pristup.Major part of the cultural heritage consists of objects of organic, plant material, canvas. As such, they are highly susceptible to fungal contamination, which by its action accelerate the deterioration of the canvas. One of the most suitable methods to stop the destructive action of fungi is gamma radiation. This paper investigates the resistance of linen mycobiota to gamma radiation as well as the resistance of the inoculated secondary colonizer type Cladosporium sphaerospermum. The samples were treated with a source at the Laboratory for radiation chemistry and dosimetry of Ruđer Bošković Institute. Absorption doses of 2, 7, 20 and 50 kGy were applied at two radiation rates of 0,1 and 8,6 Gy/s. Microbiological analysis of irradiated samples was carried out immediately after radiation and on the 14th, 28th and 56th day after radiation.
Natural mycobiota of linen material includes species from the genera Penicillium, Cladosporium, Fusarium and yeast. The antifungal effect of gamma radiation is dependent on dose and dose rate. Fusarium spp., orange yeasts and Cladosporium spp. proved to be the most resistant to gamma radiation. The test results also set D10 value of 13,72 kGy for higher radiation rate (8,6 Gy/s). A chemical analysis of the linen material should be carried out in order to obtain better insight into the impact of certain doses and the radiation rates on the composition of the canvas. An interdisciplinary approach is required for the effective application of gamma radiation in the conservation of canvas objects of cultural heritage