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Objectives: The goal of this study was to analyze the quality of abstracts of RCTs regarding melatonin and sleep disorders. Materials and methods: This study assessed the reporting quality of abstracts on PubMed for melatonin and sleep RCTs. A search yielded 232 abstracts, with 13 exclusions. The CONSORT for abstracts checklist was used to assess various aspects including study design, methods, results and conclusions. Data was analyzed using MedCalc software. Results: Of the 232 abstracts initially found, 13 were excluded, leaving 219 abstracts for analysis. The median CONSORT score was 7, with a range of 6-9. Abstracts from higher ranked journals had higher scores. Significant differences in reporting were found between abstracts with significant and non-significant results. The most common components found in the abstracts were the objective, intervention and outcome, demonstrating their inherent importance. Conversely, aspects such as funding, type of randomization and trial registration were under-reported, suggesting opportunities for improvement. Conclusion: The review of abstracts from a PubMed search on melatonin and sleep revealed moderate reporting quality according to CONSORT. Notably, abstracts published in the top quartile had the highest CONSORT scores, while those in journals not indexed in the Web of Science (without quartile) had comparatively lower scores, highlighting the influence of journal prestige on reporting standards., Cilj istraživanja: Cilj ovog istraživanja bio je analizirati kvalitetu sažetaka RCT-ova koji se odnose na melatonin i poremećaje spavanja. Materijal i metode: Ova studija procijenila je kvalitetu izvješćivanja sažetaka na PubMedu za melatonin i RCT-ove spavanja. Pretraživanje je dalo 232 sažetka, s 13 isključenja. Kontrolni popis CONSORT za sažetke korišten je za procjenu različitih aspekata uključujući dizajn studije, metode, rezultate i zaključke. Podaci su analizirani pomoću softvera MedCalc. Rezultati: Od ukupno pronađenih 232 sažetka, isključeno je 13, ostavljajući 219 sažetaka za analizu. Medijan CONSORT bodova bio je 7, s rasponom od 6 do 9. Sažetci iz časopisa višeg ranga imali su više bodova. Utvrđene su značajne razlike u izvještavanju između sažetaka s značajnim i nesignifikantnim rezultatima. Najčešći elementi u sažecima bili su cilj, intervencija i ishod, što ukazuje na njihovu inherentnu važnost. Nasuprot tome, aspekti poput financiranja, vrste randomizacije i registracije ispitivanja bili su nedovoljno prikazani, što ukazuje na mogućnosti za poboljšanje. Zaključak: Pregled sažetaka dobivenih pretragom na PubMedu o melatoninu i spavanju otkrio je umjereni kvaliteta izvještavanja prema CONSORT-u. Posebno se ističe da su sažetci objavljeni u prvom kvartilu imali najviše CONSORT bodova, dok su oni u časopisima koji nisu indeksirani u Web of Science-u (bez kvartila) imali relativno niže bodove, što naglašava utjecaj ugleda časopisa na standarde izvještavanja.

Objectives: The aim of this study was to assess the reporting quality of randomized controlled trial abstracts on topical vitamin C. Materials and Methods: We conducted a comprehensive analysis of randomized controlled trials focused on local vitamin C. The quality of abstracts was assessed using the CONSORT checklist, which consists of 17 items. Results: During the observation period, there was no significant increase in the number of studies on the topical use of vitamin C products over the years. The proportion of articles in each year was 5.5%. The total CONSORT score ranged from 0 to 13 out of a possible 17 points, with a median score of 7 and an interquartile range of 5-9. The least frequently reported items were information on funding sources (2.8%) and randomization criteria (4.6%). There were significant differences between structured and unstructured abstracts in the reporting of several CONSORT items. Structured abstracts were more likely to include the term "RCT" in the title (67.9% vs. 32.1%, P=0.012). The last item for which a significant difference was observed was trial registration, with structured abstracts more likely to report the trial registration number and the name of the trial registry (100.0% vs 0%, P=0.032). Conclusion: Analysis of abstracts on the use of topical vitamin C indicates that the quality of abstracts in this area is generally low. The CONSORT checklist has proven to be a valuable tool for improving the readability, transparency, and reliability of articles. As more journals adopt CONSORT as their publication standard, it is desirable that it be used in the field of cosmetology., Naslov: Kvaliteta sažetaka randomiziranih kontroliranih ispitivanja topikalnog vitamina C. Ciljevi: Cilj ovog istraživanja je bio procijeniti kvalitetu sažetaka randomiziranih kontroliranih ispitivanja pokusa koji su ispitivali učinak topikalno korištenog vitamina C. Metode: Proveli smo presječnu analizu randomiziranih kontroliranih ispitivanja koja su se usredotočila na lokalni vitamin C. Kvaliteta sažetaka procijenjena je CONSORT kontrolnom listom koja se sastoji od 17 stavki. Rezultati: U promatranom periodu nije uočeno značajno povećanja broja istraživanja o lokalnoj uporabi proizvoda s vitaminom C tijekom godina. Udio članaka u svakoj godini bio je 5,5%. Ukupni rezultat CONSORT-a kretao se od 0 do 13 od 17 mogućih bodova, s medijanom rezultata od 7 i interkvartilnim rasponom od 5-9. Najrjeđe prijavljene stavke bile su informacije o izvorima financiranja (2,8%) i kriterijima randomizacije (4,6%). Postojale su značajne razlike između strukturiranih i nestrukturiranih sažetaka u izvješćivanju nekoliko CONSORT stavki. Strukturirani sažeci češće uključuju izraz "RCT" u naslovu (67,9% u odnosu na 32,1%, P=0,012). Posljednja stavka u kojoj je uočena značajna razlika bila je registracija ispitivanja, sa strukturiranim sažecima koji pokazuju jasniji registracijski broj i naziv registra ispitivanja u usporedbi s nestrukturiranim sažetcima (100,0% naspram 0%, P=0,032). Zaključak: Analiza sažetaka o korištenju lokalnog vitamina C pokazuje da je kvaliteta sažetaka u ovom području općenito niska. Kontrolni popis CONSORT pokazao se kao vrijedan alat za poboljšanje čitljivosti, transparentnosti i pouzdanosti članaka. Kako sve više časopisa usvaja CONSORT kao svoj standard objavljivanja, poželjno je da se koristi i u području kozmetologije.

Contains fulltext : 290819.pdf (Publisher’s version ) (Open Access) At the 2015 World Health Assembly, UN member states adopted a resolution that committed to the development of national action plans (NAPs) for antimicrobial resistance (AMR). The political determination to commit to NAPs and the availability of robust governance structures to assure sustainable translation of the identified NAP objectives from policy to practice remain major barriers to progress. Inter-country variability in economic and political resilience and resource constraints could be fundamental barriers to progressing AMR NAPs. Although there have been regional and global analyses of NAPs from a One Health and policy perspective, a global assessment of the NAP objectives targeting antimicrobial use in human populations is needed. In this Health Policy, we report a systematic evidence synthesis of existing NAPs that are aimed at tackling AMR in human populations. We find marked gaps and variability in maturity of NAP development and operationalisation across the domains of: (1) policy and strategic planning; (2) medicines management and prescribing systems; (3) technology for optimised antimicrobial prescribing; (4) context, culture, and behaviours; (5) operational delivery and monitoring; and (6) patient and public engagement and involvement. The gaps identified in these domains highlight opportunities to facilitate sustainable delivery and operationalisation of NAPs. The findings from this analysis can be used at country, regional, and global levels to identify AMR-related priorities that are relevant to infrastructure needs and contexts.

Cilj: Procijeniti spremnost za racionalno propisivanje antimikrobnih lijekova među diplomantima četiriju hrvatskih medicinskih fakulteta temeljem samoprocjene. Nadalje, ustvrditi i raspraviti eventualno prisutne nejednakosti među edukacijskim kurikulumima medicinskih fakulteta. Ispitanici i metode: Svi studenti završne godine studija na svim četirima hrvatskim medicinskim fakultetima (Osijek, Rijeka, Split i Zagreb) mogli su sudjelovati u ovom presječnom istraživanju. Korišten je validirani upitnik radne skupine ESGAP Student-PREPARE. Riječ je o upitniku od 47 čestica, a uključuje pitanja o demografskim odrednicama, samoprocijenjenoj spremnosti za racionalno propisivanje antimikrobnih lijekova, percepciji o korisnosti različitih metoda poučavanja te percipiranoj potrebi za daljnjom edukacijom iz ove tematike. Rezultati: Stopa odaziva po pojedinim fakultetima bila je u rasponu od 15,71% do 31,33%. Razina samoprocijenjene „sveukupne spremnosti“ (engl. global preparedness score, GPS) za racionalno propisivanje antimikrobnih lijekova po fakultetima iznosila je redom: Osijek 48,82; Zagreb 53,56; Rijeka 57,14 te Split 66,28. Prosječni GPS (56,45) u 2019. u Hrvatskoj nije bio statistički značajno različit od vrijednosti u 2015. godini (62,66). Splitski su studenti imali statistički značajno bolje rezultate u 3/27 kurikularnih područja, dok za preostala područja statistički značajna razlika nije pronađena. Većina je diplomanata (73,68% – 100%) izrazila potrebu za dodatnom edukacijom iz ove tematike. Samoprocijenjena dostupnost/korisnost interaktivnijih metoda poučavanja bila je veća na splitskom fakultetu. Zaključak: Hrvatski diplomanti medicine po završetku studija generalno se ne osjećaju dovoljno spremnima za samostalno propisivanje antimikrobnih lijekova koje im predstoji u skorašnjoj kliničkoj praksi. Osjetne interregionalne diskrepancije u spremnosti studenata za racionalno propisivanje antimikrobnih lijekova nisu pronađene, međutim uočene su značajnije razlike po pitanju samoprocijenjene dostupnosti/korisnosti pojedinih metoda poučavanja među fakultetima., Aim: To assess self-reported preparedness for prudent antimicrobial use in final-year medical students in Croatia, and to determine possible inconsistencies in educational curricula in four Croatian medical schools. Participants and methods: All 2019 graduates were eligible to participate in this cross-sectional study at four Croatian medical schools (Osijek, Rijeka, Split, and Zagreb). The utilized questionnaire was developed by ESGAP Student-PREPARE Working Group. The 47-item questionnaire included questions on demographics, selfreported preparedness regarding prudent antimicrobial use, perceptions of the usefulness of teaching methods and perceived need for further education. Results: Response rates varied by medical school from 15.71% to 31.33%. Global preparedness scores (GPS; self-reported preparedness regarding prudent antimicrobial use) for Osijek, Zagreb, Rijeka and Split medical schools were: 48.82, 53.56, 57.14 and 66.28, respectively. Average GPS for Croatia in 2019 was 56.45, with no statistically significant difference from 2015 (62.66). A statistically significant difference was observed for 3/27 curriculum topics on prudent antimicrobial use, all in favour of Split medical students. Most students (73.68%–100%) reported requiring more/further education on antimicrobial use. A higher self-reported availability/usefulness of the more interactive teaching methods was reported for Split Medical School. Conclusion: Croatian medical students who are about to start prescribing antimicrobials on their own, generally still do not feel sufficiently prepared to do so adequately. In 2019 no noticeable interregional discrepancies were found in self-reported preparedness for prudent antimicrobial use. Greater differences were observed in perceived usefulness of teaching methods between medical schools.

Ciljevi: Primarni cilj provedenog istraživanja bio je utvrditi učestalost primjene i vrstu kortikosteroidne terapije COVID-19 bolesnika hospitaliziranih u KBC-u Split. Sekundarni cilj bio je pokazati korelaciju primjene kortikosteroidne terapije s komorbiditetima, odabranim laboratorijskim nalazima i smrtnim ishodom. Ispitanici i postupci: Retrospektivno istraživanje dio je multicentrične studije i provedeno je na kohorti od 282 bolesnika hospitaliziranih na Klinici za infektologiju u Splitu tijekom studenog i prosinca 2020. godine. Za svakog ispitanika pretraživano je 244 stavki iz otpusnih pisama, a u analizu su uključene varijable: dob i spol ispitanika, broj dana provedenih u bolničkom liječenju, podatci o prethodnom pobolijevanju, primijenjena kortikosteroidna terapija, dijagnosticirana pneumonija, vrijednost saturacije periferne krvi kisikom, vrijednosti sistoličkog i dijastoličkog arterijskog tlaka te laboratorijski nalazi: koncentracija ureje, kreatinina, ukupnog bilirubina, D-dimera te udjeli neutrofila i limfocita. Rezultati: Podatci o primjeni kortikosteroidne terapije odnose se na sve ispitanike uključene u istraživanje. Većina je ispitanika bila liječena kortikosteroidima (N = 214 (80%)). Pneumonija je dijagnosticirana u većine ispitanika kojima je primijenjena kortikosteroidna terapija. Saturacija periferne krvi kisikom bila je značajno niža kod ispitanika koji su primali kortikosteroidnu terapiju te je bila jednoliko raspodijeljena među spolovima. Kortikosteroid izbora bio je deksametazon, primijenjen u 169 (60%) bolesnika. Drugi najčešće primijenjeni kortikosteroid bio je metilprednizolon, primijenjen u 53 (19%) bolesnika. Samo jedan bolesnik liječio se hidrokortizonom (0,4%). Višestruku kortikosteroidnu terapiju primalo je 9 bolesnika. Koncentracija ureje, kreatinina, ukupnog bilirubina te D-dimera nije se razlikovala među bolesnicima obzirom na primjenu kortikosteroidne terapije. Bolesnici na kortikosteroidnoj terapiji nisu imali više komorbiditeta u odnosu na bolesnike bez terapije. Zaključci: Bolesnici na kortikosteroidnoj terapiji češće su imali više simptoma COVID-19 bolesti pri prijemu u bolnicu, češće su bolovali od pneumonije i imali hipoksemiju. Omjer neutrofila i limfocita bio je niži u ovih bolesnika. Unatoč tome što je arterijska hipertenzija bila učestali komorbiditet, arterijski tlak nije se razlikovao među bolesnicima koji uzimaju ili ne uzimaju kortikosteroidnu terapiju. Primjena kortikosteroidne terapije nije bila povezana s komorbiditetima niti sa smrtnim ishodom. Objectives: The primary objective of the research was to determine the frequency of use and type of corticosteroid therapy for COVID-19 patients hospitalized at the University Hospital Center Split. The secondary objective was to determine the correlation of corticosteroid therapy with comorbidities, selected laboratory findings, and death. Subjects and procedures: This retrospective study is part of a multicenter study and was conducted on a cohort of 282 patients hospitalized at the Clinic for Infectious Diseases in Split during November and December 2020. For each subject, 244 items from the discharge letters were searched, and the variables included in the analysis were age and sex of the patient, number of days receiving treatment in the hospital, data on previous illness, receipt of corticosteroid therapy, diagnosed pneumonia. Additionally, measurements of peripheral blood oxygen saturation, systolic and diastolic arterial pressure, and laboratory findings, including the concentration of urea, creatinine, total bilirubin, D-dimer, and proportions of neutrophils and lymphocytes were assessed. Results: Data on the use of corticosteroid therapy refer to all subjects included in the study. Most subjects were treated with corticosteroids (N = 214 [80%]). Pneumonia was diagnosed in the majority of subjects who received corticosteroid therapy. Peripheral blood oxygen saturation was significantly lower in subjects receiving corticosteroid therapy and was equally distributed between the sexes. The corticosteroid of choice was dexamethasone used by 169 (60%) patients. The second most frequently used corticosteroid was methylprednisolone used by 53 (19%) patients. Only one patient was treated with hydrocortisone (0.4%). 9 patients received multiple corticosteroid therapy. The concentration of urea, creatinine, total bilirubin, and D-dimer did not differ between patients regarding their use of corticosteroid therapy. Patients on corticosteroid therapy did not have more comorbidities compared to patients without therapy. Conclusions: Patients on corticosteroid therapy more often had more symptoms of COVID-19 when admitted to the hospital, more often suffered from pneumonia, and had hypoxemia. The ratio of neutrophils to lymphocytes was lower in these patients. Although arterial hypertension was a frequent comorbidity, the arterial pressure did not differ between patients taking and not taking corticosteroid therapy. The use of corticosteroid therapy was not associated with comorbidities or death.

Ciljevi istraživanja: U modelu jedne umjerene traumatske ozljede mozga (engl. traumatic brain injury, TBI) odrediti pojavnost i opseg izražaja TDP-43 u ipsilateralnom i kontralateralnom korteksu i hipokampusu, usporediti TDP-43 subcelularni izražaj nakon jedne umjerene TBI i blage repetitivne TBI (engl. repetitive mild traumatic brain injury, rmTBI), te odrediti povezanost TDP-43 izražaja s biljezima sinaptogeneze i upale nakon TBI. Materijal i metode: Metodom lateralne ozljede tlakom tekućine (engl. lateral fluid percussion injury, LFPI) izazvana je jedna TBI umjerene jakosti u miša, dok je metodom pada utega izazvana rmTBI. Izražaj proteina od interesa analiziran je u citoplazmatskim i nuklearnim frakcijama ipsilateralnog i kontralateralnog korteksa i hipokampusa u životinja LFPI skupina, te frontalnom korteksu i hipokampusima rmTBI miševa. Histološkim tehnikama praćene su moždane promjene, a imunofluorescentnim tehnikama subcelularna lokalizacija TDP-43 te povezanost s biljezima upale i sinaptogeneze. Rezultati: Ipsilateralni korteks LFPI životinja najoštećenija je moždana struktura koju prati dezintegracija bijele tvari. U ipsilateralnom korteksu pronađena je translokacija TDP-43 u citoplazmu prvog i trećeg dana nakon LFPI u neuronima i mikrogliji. U ipsilateralnom hipokampusu uočen je pad izražaja nuklearnog TDP-43 trećeg dana od jedne umjerene TBI. Četrnaest dana nakon jedne umjerene LFPI, ali i rmTBI uočen je porast izražaja nuklearnog TDP-43 u ipsilateralnom, odnosno frontalnom korteksu. Detektiran je porast izražaja fragmentiranog TDP-35 te značajan porast izražaja fosforiliranih oblika P-TDP-43 i P-TDP-35 u ipsilateralnom hipokampusu četrnaest dana nakon jedne LFPI, ali ne i u hipokampusu rmTBI životinja. U ipsilateralnom korteksu LFPI životinja uočena je povezanost biljega upale NF-κB i TDP-43 trećeg dana u području uz najveće oštećenje te povećan izražaj biljega iNOS prvog dana uz povezanost s TDP-43 u području najvećeg oštećenja. Pad izražaja PSD-95 uz gubitak neurona ipsilateralnog korteksa praćen je pozitivnom korelacijom s TDP-43 prvog, trećeg i četrnaestog dana od LFPI. Porast izražaja proteina APP uočen je subakutno samo u rmTBI skupini životinja, a proteina P-tau samo u LFPI miševa. Zaključak: Jedna umjerena LFPI uzrokuje deregulaciju TDP-43 u ipsilateralnom korteksu i hipokampusu koja utječe na pojedine biljega upale i sinaptogeneze. Navedene promjene ovise o zadobivenoj traumi mozga i od potencijalne su važnosti u farmakoterapiji TBI., Objectives: To determine the incidence and extent of TDP-43 expression of the ipsilateral and contralateral cortex and hippocampus after a single moderate traumatic brain injury (TBI), compare TDP-43 subcellular localization after single moderate TBI and repetitive mild traumatic brain injury (rmTBI), and determine the association of TDP-43 expression with markers of synaptogenesis and inflammation after TBI. Material and methods: Lateral fluid percussion injury (LFPI) was used to induce the single moderate TBI, while the weight drop method was used to cause the rmTBI. The levels of expression of proteins of interest were analyzed in the cytoplasmic and nuclear fractions of the ipsilateral and contralateral cortex and hippocampus in the animals of the LFPI and in the frontal cortex and the hippocampi of rmTBI mice. Histological techniques were used to determine brain changes, and immunofluorescent techniques were used to monitor the subcellular localization of TDP-43 and its association with some markers of inflammation and synaptogenesis. Results: The ipsilateral cortex of the LFPI group is the most damaged brain structure accompanied by white matter disintegration. Also, a translocation of TDP-43 into the cytoplasm was detected on the first and third day after LFPI in the neurons and microglia of the ipsilateral cortex. In the ipsilateral hippocampus, a decrease in the expression of nuclear TDP-43 was found on the third day after one moderate TBI. Fourteen days after LFPI and rmTBI, an increase in nuclear TDP-43 expression was observed in the ipsilateral and frontal cortex, respectively. Significant increases in the expression of TDP-35, P-TDP-43 and P-TDP-35 were detected subacutely only in the ipsilateral hippocampus of the LFPI animals. The association with inflammation marker NF-κB and TDP-43 was found around the area of the greatest cortical damage. Also, significant iNOS expression with the interconnection with TDP-43 was evident in the ipsilateral cortex on the first day after LFPI. The decline in PSD-95 expression with loss of ipsilateral cortical neurons was followed by a positive correlation with TDP-43 on the first, third and fourteenth day after LFPI. An increase in APP protein expression was observed subacutely only in the rmTBI group of animals, and P-tau protein only in the LFPI mice. Conclusion: One moderate LFPI causes deregulation of TDP-43 in the ipsilateral cortex and hippocampus and it is related to some markers of inflammation and synaptogenesis. These changes depend on the type of the acquired brain trauma and are of potential importance in TBI pharmacotherapy.

Objectives: The aim of this study was to evaluate the available RCTs and systematic reviews regarding the efficacy and safety of antioxidant vitamin supplementation in preventing and slowing the progression of age-related cataract and to examine if we could find enough evidence for this. Materials and methods: The Cochrane systematic review “Antioxidant vitamin supplementation for preventing and slowing the progression of age-related cataract” was used as a base and according to its inclusion criteria we tried to find RCTs and systematic reviews published after it, yielding additional proof of the safety and efficacy of antioxidant vitamin supplementation regarding age-related cataracts. We searched PubMed, CENTRAL and DARE. After the search, we made a quality assessment of the systematic review using RAMSTAR. Results: The Cochrane systematic review involved nine trials, with 117,272 participants overall and an age range of ≥ 35 years. The trial follow-up ranged from 2.1 to 12 years and the trials were conducted in Italy, Finland, the United Kingdom, Australia, India and the United States. The antioxidant vitamins were dosed above the recommended daily allowance. No evidence was found supporting that antioxidant vitamin supplementation could reduce the risk of progression of cataract, cataract development, cataract extraction or that it could slow the loss of visual acuity. No evidence of effect of supplementation of beta-carotene in reducing the risk of cataract could be found in the pooled analysis (RR 0.99, 95%, CI 0.91-1.08; number of participants: 57,703) nor could be evidence found for a reduction of the risk of cataract extraction (RR 1.00, 95% CI 0.91-1.10; number of participants: 86,836). For the supplementation with vitamin E no risk reduction in cataract incidence could be found in the pooled analysis either (RR 0.97, 95% CI 0.91-1.04; number of participants: 50,059) or of cataract extraction (RR 0.98, 95% CI 0.91 - 1.05; number of participants: 83,956). 7.4 - 15.8% of patients on beta-carotene developed hypercarotenodermia (yellowing of skin). Only one additional RCT was found involving 11,267 exclusively male participants from the United States, Canada and Puerto Rico, with an age range of 50 years and older. Only part of this RCT was of interest for us, the part concerning supplementation with vitamin E. It lasted 5.6 years. Conclusion: Not enough evidence could be found to prove the safety and efficacy of supplementation with antioxidant vitamins for the slowing and the prevention of age-related cataract. Further research among non-well-nourished populations or well-nourished populations but regarding antioxidant blood levels rather than supplementation could be conducted in the future., Ciljevi: Cilj ove studije bio je procijeniti dostupne RCT-ove i sustavne preglede koji se odnose na učinkovitost i sigurnost suplementacije vitamina antioksidansa u prevenciji i usporavanju napredovanja katarakte povezane sa starenjem te ispitati možemo li pronaći dovoljno dokaza za to. Materijali i metode: Cochraneov sustavni pregled „Dopuna antioksidativnim vitaminima za prevenciju i usporavanje napredovanja katarakte povezane sa starenjem” korišten je kao osnova i prema njegovim kriterijima za uključivanje pokušali smo pronaći RCT-ove i sustavne preglede objavljene nakon Cochranovom sustavnom pregledu, koji su dali dodatne dokaze o sigurnost i učinkovitosti antioksidativnih vitaminskih suplementacija u pogledu katarakte povezane sa starenjem. Pretražili smo PubMed, CENTRAL i DARE. Nakon pretrage napravili smo procjenu kvalitete sistematskog pregleda pomoću R-AMSTAR-a. Rezultati: Cochrane sustavni pregled uključivao je devet ispitivanja s ukupno 117 272 osobe u dobi od 35 godina i više. Praćenje ispitivanja kretalo se od 2,1 do 12 godina, a ispitivanja su provedena u Australiji, Finskoj, Indiji, Italiji, Ujedinjenom Kraljevstvu i Sjedinjenim Državama. Doze antioksidativnih vitamina premašile su preporučenu dnevnu dozu. Nije bilo dokaza o učinku dodataka vitamina antioksidansa u smanjenju rizika od katarakte, ekstrakcije katarakte, progresije katarakte ili usporavanja gubitka vidne oštrine. U zbirnim analizama nije bilo dokaza o učinku suplementacije beta-karotena u smanjenju rizika od katarakte (dva ispitivanja) (relativni rizik 0,99, 95% interval pouzdanosti 0,91-1,08; broj ispitanika 57 703) ili u smanjenju rizika od ekstrakcije katarakte (tri ispitivanja). Udio sudionika koji su razvili hiperkarotenodermiju (žutilo kože) dok su uzimali beta-karoten kretao se od 7,4% do 15,8%. Pronađen je samo jedan dodatni RCT koji je uključivao 11.267 isključivo muških sudionika iz Sjedinjenih Država, Kanade i Portorika, s dobnim rasponom od 50 godina i više. Zanimao nas je samo dio ovog RCT-a, dio koji se odnosi na suplementaciju vitaminom E. Trajao je 5,6 godina. Zaključak: Ne može se pronaći dovoljno dokaza za sigurnost i učinkovitost antioksidativnih vitaminskih suplemenata za prevenciju i usporavanje katarakte povezane sa starenjem. U budućnosti bi se mogla provesti daljnja istraživanja među neuhranjenim ili dobro uhranjenim stanovništvom, ali u vezi s razinama antioksidansa u krvi, a ne suplementaciji.

Konoplja (lat. Cannabis) je biljka čija je primjena u medicinske svrhe poznata stoljećima. Postoje dvije vrste ove biljke, Cannabis sativa i Cannabis indica. Prva se kroz dugu povijest koristila kao medicinski pripravak za liječenje brojnih bolesti. Zbog njezinog psihoaktivnog učinka koristila se i kao droga te je zbog toga bila na popisu supstancija čije je korištenje i prodaja ilegalno. Otkrićem njezinih aktivnih supstanci, kanabinoida THC-a, CBD-a i CBN-a, započelo je istraživanje njihovih farmakoloških učinaka kao i ponovno korištenje u terapijske svrhe. Aktivne tvari učinak ostvaraju putem endokanabinoidnog sustava u čovjeka. Dosada su provedena brojna klinička istraživanja koja su dokazala pozitivan učinak u liječenju neuroloških bolesti, karcinoma i HIV/AIDS-a. Odobrene su indikacije za korištenje u tim bolestima te registrirani lijekovi na bazi konoplje i kanabinoida. Problem u širem korištenju predstavljaju nuspojave tih lijekova kao i njihovo doziranje koje je standardizirano, ali doze različito utječu na pojedine bolesnike te je nužna individualna prilagodba. Medicinska primjena lijekova na bazi konoplje i kanabinoida i dalje je predmet brojnih kliničkih istraživanja. Postoji terapijski potencijal u brojnim drugim bolestima, no rezultati učinka na velikom broju pacijenata i analiza doziranja su neophodni za odobrenje dodatnih indikacija., Hemp (lat. Cannabis) is a plant whose use for medicinal purposes has been known for centuries. There are two species, Cannabis sativa and Cannabis indica. The first has long been used as a medicinal preparation for the treatment of many diseases. Due to its psychoactive effect, it was also used as a drug and was therefore on the list of substances whose use and sale is illegal. With the discovery of its active substances, the cannabinoids THC, CBD and CBN, research into their pharmacological effects as well as re-use for therapeutic purposes began. The active substances have an effect through the endocannabinoid system in humans. So far, numerous clinical studies have been conducted that have proven to have a positive effect in the treatment of neurological diseases, cancer and HIV / AIDS. Indications for use in these diseases have been approved and hemp and cannabinoid-based medicines have been registered. A problem in wider use is the side effects of these drugs as well as their dosage which is standardized, but the doses affect different patients differently and individual adjustment is necessary. The medical use of cannabis and cannabinoid-based drugs remains the subject of numerous clinical studies. There is therapeutic potential in a number of other diseases, but the results of effects in a large number of patients and dosing analysis are necessary to approve additional indications.

With the progress of medicine, especially in the last century, life expectancy increased considerably. As a result, age-related diseases also increased, especially malignancies and degenerative diseases of the central nervous system. The incidence and prevalence of neurodegenerative diseases steadily increased over the years, but despite efforts to uncover the pathophysiological processes behind these conditions, they remain elusive. Among the many theories, oxidative stress was proposed to be involved in neurodegenerative processes and to play an important role in the morbidity and progression of various neurodegenerative disorders. Accordingly, a number of studies discovered the potential of natural plant constituents to have significant antioxidant activity. This review focused on several plant-based antioxidants that showed promising results in the prevention and treatment of neurodegenerative diseases. Laurus nobilis, Aronia melanocarpa, and celastrol, a chemical compound isolated from the root extracts of Tripterygium wilfordii and T. regelii, are all known to be rich in antioxidant polyphenols.

The central nervous system (CNS) injury, which occurs because of mechanical trauma or ischemia/hypoxia, is one of the main causes of mortality and morbidity in the modern society. Until know, despite the fact that numerous preclinical and clinical studies have been undertaken, no significant neuroprotective strategies have been discovered that could be used in the brain trauma or ischemia treatment. Although there are many potential explanations for the failure of those studies, it is clear that there are questions regarding the use of experimental models, both in vivo and in vitro, when studying CNS injury and searching new therapeutics. Due to some ethical issues with the use of live animals in biomedical research, implementation of experimental strategies that prioritize the use of cells and tissues in the in vitro environment has been encouraged. In this review, we examined some of the most commonly used in vitro models and the most frequently utilized cellular platforms in the research of traumatic brain injury and cerebral ischemia. We also proposed some future strategies that could improve the usefulness of these studies for better bench-to-bedside translational outcomes.

Arterijska elastičnost neovisan je pokazatelj kardiovaskularnog rizika koji se lako mjeri neinvazivnim metodama. U uzorku opće populacije (n=1012) napravili smo usporedbu podudarnosti pokazatelja arterijske elastičnosti izmjerenih metodama tonometrije i oscilometrije. Analizirani su augmentacijski indeksi i centralni tlakovi. Unatoč dobroj inicijalnoj korelaciji među uređajima SphygmoCor (tonometrija) i Arteriograph (oscilometrija), grafičkom usporedbom rezultata augmentacijskog indeksa prikazali smo neravnomjerno odstupanje od pravca podudarnosti. Detaljnom analizom podataka utvrdili smo da uređaji nisu međusobno zamjenjivi jer na njih različito utječu odrednice arterijske elastičnosti, pretežito dobi. Nadalje, ispitana je primjenjivost normativnih formula za centralni augmentacijski indeks (cAIx) izvedenih iz danske populacije niskog kardiovaskularnog rizika koristeći odgovarajuću hrvatsku populaciju iz mediteranskog područja. Raspodjela stvarno izmjerenog cAIx-a, dobi i predviđenih vrijednosti cAIx-a hrvatske populacije bila je visoko usporediva sa danskim uzorkom. Međutim, predviđene vrijednosti dobivene pomoću normativnih formula pokazuju poprilično velike raspone u interindividualnim vrijednostima, te stoga nisu jednako primjenjive za sve dobne skupine. Dizajniranjem za uže dobne skupine, poboljšala bi se osjetljivost formula u otkrivanju rizičnih vaskularnih fenotipova, smanjilo utjecaj neujednačene dobne distribucije između populacija te uopće olakšala interpopulacijska usporedba. Naposljetku smo, na odabranoj skupini bolesnika (n=38) sa opstrukcijskom apnejom tijekom spavanja pratili dugoročne promjene arterijske elastičnosti primjenom terapije adaptivnim pozitivnim tlakom zraka u trajanju od godine dana. Rezultat je značajno sniženje brzine pulsnog vala i centralnog sistoličkog tlaka u usporedbi s početnim vrijednostima, s najvećim poboljšanjem postignutim tijekom prvih 6 mjeseci terapije., Arterial stiffness is an independent predictor of cardivascular risk easily assesed with non-invasive methods. In a general population sample (n=1012) we compared the agreement of arterial stiffness indices measured by the methods of tonometry and oscillometry. Augmentation index and central systolic pressure were analysed. Despite a good inital corelation between the devices (SphygmoCor – tonometry and Arteriograph – oscilometry), a graphic comparison of the augmentation index reaveald an uneven deviation from the referent line of agreement. A detailed analisys of this finding confirmed the devices as not interchangeble because they seem to be differently influenced by predictors of arterial stiffness, predominately by age. Secondly, examined was aplicability of normative equations for central augmentation index (cAIx) derived from Danish population with low cardiovascular risk on the corresponding Croatian population from the Mediterranean area. Both, cAIx-age distribution and normative equation fitted on Croatian data were highly comparable to Danish sample. However, the equations do not equally hold true across age ranges and tolerate rather wide range of individual variability in cAIx values. If designed for narrower age groups, the equations' sensitivity in detecting vascular phenotypes at risk could be improved, the impact of difference in sampling frame largely reduced and applicability on different populations facilitated. Finally, on a selected cohort of obstructive sleep apnea patients (n=38) we evaluated effects of a long term adaptive positive air presseure therapy on arterial stiffness during one year follow-up. Relative to the inital values a significant reduction in pulse wave velocity and central systolic pressure was observed. Majority of the effects occured during the first 6 months of therapy.

Dijabetes (Diabetes mellitus) je ozbiljna, za sada neizlječiva, kronična bolest koja je okarakterizirana hiperglikemijom kao i poremećajima u metabolizmu ugljikohidrata, masti i proteina. U zadnja dva desetljeća se drastično povećala incidencija ove bolesti, pretežito kod osoba starije dobne skupine, ali ne zaobilazi niti mlađu populaciju. Upravo zbog toga je sve više istraživanja usmjereno na razvoj novih, dostupnijih i učinkovitijih metoda terapijskog liječenja. U ovom diplomskom radu je ispitivan učinak rekombinantnog humanog eritropoetina (rhEPO) na ekspresiju i aktivnost SIRT1 proteina (engl. silent information regulator two protein 1), ekspresiju proBDNF i mBDNF proteina kao i na IkBα protein u parijatalnom korteksu i/ili hipokampusu štakora s eksperimentalnim dijabetesom. Hannover Wistar štakorima muškog spola je izazvan dijabetes primjenom pojedinačne injekcije streptozotocina (STZ). Dio životinja koje su razvile dijabetes primile su rhEPO (40 µg/kg tjelesne težine) (Diab/EPO) ili otapalo (Diab) četiri dana uzastopno. Kontrolnu skupinu sačinjavale su zdrave, netretirane životinje. Dobiveni rezultati pokazuju da je primjena rhEPO izazvala statistički značajan porast ekspresije SIRT1 proteina u mozgovima štakora s eksperimentalnim dijabetesom u korteksu i hipokampusu u usporedbi sa kontrolnom skupinom štakora i skupinom štakora tretiranih s otapalom (Diab). Zabilježen je i statistički značajan porast ekspresije proBDNF, ali ne i mBDNF proteina u parijetalnom korteksu životinja. Ekspresija proteina IkBα je porasla kod skupine životinja tretiranih s rhEPO, ali dobiveni podaci nisu statistički značajni., Diabetes mellitus is a serious, incurable, chronic disease characterised by hyperglycaemia and disorders in the metabolism of carbohydrates, fats and proteins. The incidence of this disease has increased drastically over the past decades, mostly in the elderly, but it does not bypass the younger population. Therefore, more and more research is focused on the development of new, more accessible and more efficient ways of therapeutic treatment. The effect of recombinant human erythropoietin (rhEPO) on expression and activity of SIRT1 protein (silent information regulator two protein 1), proBDNF and mBDNF protein expression as well as on IkBα protein in the pariatric cortex and/or hippocampus of rats with experimental diabetes were researched in this study. Diabetes mellitus in Hannover Wistar male rats was caused by single injection of streptozotocin (STZ). Some of the animals that developed diabetes mellitus received either rhEPO (40 µg/kg body weight) (Diab/EPO) or solvent (Diab) for four consecutive days. The control group consisted of healthy, untreated animals. The results showed that the use of rhEPO induced a statistically significant increase in SIRT1 protein expression in the brains of rats with experimental diabetes in the cortex and hippocampus compared to the control group of rats and the solvent treated group of rats (Diab). There was also a statistically significant increase in proBDNF expression, but not of mBDNF protein in the parietal cortex of animals. IkBα protein expression increased in the group of animals treated with rhEPO, but the data obtained are not statistically significant.

Moždani udar je cerebrovaskularni poremećaj karakteriziran kliničkim znakovima brzog razvoja žarišnih ili globalnih poremećaja cerebralne funkcije. Jedan je od vodećih uzroka invalidnosti i smrtnosti u svijetu uz vrlo ograničene terapijske mogućnosti. Više od 80% moždanih udara je ishemijskog podrijetla, nastalih većinom uslijed okluzije srednje moždane arterije (engl. middle cerebral artery occlusion MCAO). U ovom diplomskom radu ispitivan je učinak rekombinantnog humanog eritropoetina (rhEpo) na ekspresiju i aktivnost SIRT 1 proteina (engl. silent information regulator two protein 1), ekspresiju iNOS-a i GFAP-a te aktivaciju mikroglije u korteksu i/ili hipokampusu štakora izloženih postupku MCAO. Hannover Wistar štakori muškog spola su bili izloženi žarišnoj cerebralnoj ishemiji primjenom metode MCAO tijekom 1 h. Ishemijskim životinjama je aplicirano ili otapalo ili rhEpo (5000 IU/kg, i.p.), 3 h nakon indukcije ishemije. Lažno operirane životinje su korištene kao kontrolna skupina. Životinje su žrtvovane 24 h nakon indukcije ishemije. Dobiveni rezultati pokazuju da je primjena rhEpo izazvala statistički značajan porast ekspresije SIRT1 proteina u korteksu ishemičnih životinja u usporedbi s kontrolnim skupinama. U radu nisu zabilježene značajnije promjene razine ekspresije iNOS-a i GFAP-a u ispitivanim regijama mozga. U hipokampusu ishemičnih životinja zabilježeno je smanjenje broja aktiviranih mikroglija stanica uslijed primjene rhEpo no dobiveni podaci nisu statistički značajni., Stroke is a cerebrovascular disorder characterized by clinical signs of rapid development of focal or global disorders of cerebral function. It is one of the leading causes of disability and mortality in the world with very limited therapeutic possibilities. More than 80% of strokes are of ischemic origin, caused mostly by middle cerebral artery occlusion (middle cerebral artery occlusion, MCAO). The purpose of this thesis was to investigate the effect of recombinant human erythropoietin (rhEpo) on the expression and activity of SIRT 1 protein (silent information regulator two protein 1), the expression of iNOS and GFAP and the activation of microglia in the cortex and / or hippocampus of rats exposed to MCAO procedure. Hannover Wistar male rats were exposed to focal cerebral ischemia using the MCAO method for 1 h. Ischemic animals were administered either a solvent or rhEpo (5000 IU / kg, i.p.), 3 h after induction of ischemia. Falsely operated animals were used as a control group. Animals were sacrificed 24 h after induction of ischemia. The obtained results show that the administration of rhEpo caused a statistically significant increase in the expression of SIRT1 protein in the cortex of ischemic animals compared to the control groups. No significant changes in the level of iNOS and GFAP expression in the examined brain regions were observed. In the hippocampus of ischemic animals, a decrease in the number of activated microglial cells was observed due to the use of rhEpo, but the obtained data are not statistically significant.

Parkinsonova bolest (engl. Parkinson’s disease, PD) najčešći je poremećaj kretanja te druga najučestalija progresivna neurodegenerativnu bolest u svijetu. Korištenjem neurotoksina 6-hidroksidopamin (engl. 6-hydroxydopamine, 6-OHDA) u in vivo i in vitro modelima PD može se doprinijeti rasvjetljavanju patogeneze PD. Terapijske opcije u liječenju PD su limitirane, a sve je veći broj znanstvenih dokaza o neuroprotektivnosti antioksidanasa poput crnoplodne aronije, odgovornih za zaštitu dubokih jezgara mozga poput substantie nigre i bazalnih ganglija. Cilj ovog istraživanja bio je utvrditi učinak tretmana ekstraktom aronije astrocita izloženih djelovanju 6-OHDA. Pokusi su učinjeni na primarnim mišjim astrocitima koji su bili izloženi tijekom 24 h različitim koncentracijama ekstrakta crnoplodne aronije (10, 50 ili 100 µg/mL). 6-OHDA je dodan u medij za uzgoj stanica tijekom sljedećih 72 h (za test laktatne dehidrogenaze, LDH) ili 24 h (za western blot analize). Razina aktivnosti LDH testirana je radi procjene učinaka tretmana na preživljenje astrocita, a Western blotom detektirana je razina izražaja pojedinih proteina od interesa. Rezultati su pokazali da tretman različitim koncentracijama ekstrakta aronije ne utječe značajno na aktivnost LDH u uzorcima medija neozlijeđenih astrocita. Uočeno je i da aplikacija 6-OHDA značajno povećava aktivnost LDH, a da su stanice pretretirane ekstraktom aronije u koncentracijama 50 i 100 μg/mL imale značajno nižu razinu aktivnosti ovog enzima. Nadalje, mjerene su razine izražaja proteina toplinskog šoka 70 (engl. heat shock protein 70, HSP70), moždanog neurotrofnog čimbenika (engl. brain derived neurotrophic factor, BDNF) te inducibilne sintaze dušikovog oksida (engl. inducible nitric oxide synthase, iNOS) u astrocita izloženih djelovanju 6-OHDA, netretiranih ili tretiranih ekstraktom aronije. Pretretman aronijom nije značajno utjecao na razine protektivnih proteina HSP70 i BDNF, ali je povećao razinu izražaja iNOS u ozlijeđenim astrocitima, no ne i statistički značajno. Ova studija ukazuje na moguće protektivne učinke ekstrakta crnoplodne aronije u in vitro modelu PD. Točan mehanizam protektivnog učinka još je uvijek nejasan te bi mogao biti predmetom daljnjih istraživanja., Parkinson’s disease (PD) is the most common movement disorder and the second most frequent progressive neurodegenerative disease in the world. Neurotoxin 6-hydroxydopamine (6-OHDA) is used in in vivo and in vitro models of PD and may contribute to elucidating the pathogenesis of this disease. Therapeutic options in the treatment of PD are limited, and there is growing scientific evidence of the neuroprotectiveness of antioxidants such as chokeberry, responsible for protecting deep brain nuclei such as substantia nigra and basal ganglia. The aim of this study was to determine the effect of treatment with chokeberry extract of astrocytes exposed to 6-OHDA. Experiments were performed on primary mouse astrocytes that were exposed during 24 h to different concentrations of chokeberry extract (10, 50 or 100 µg/mL). 6-OHDA was added to the cell culture medium over the next 72 h (for lactate dehydrogenase test, LDH) or 24 h (for western blot analysis). The level of LDH activity was tested to determine the effects of treatments on astrocyte survival. Western blot analysis detected the level of expression for some proteins of interest. The results of this study showed that treatment with different concentrations of chokeberry extract did not significantly affect LDH activity in media samples of uninjured astrocytes. Also, it was observed that the application of 6-OHDA significantly increased the activity of LDH, and that the cells treated with chokeberry extract at concentrations of 50 and 100 μg/mL had a significantly lower activity of this enzyme. Furthermore, heat shock protein 70 (HSP70), brain derived neurotrophic factor (BDNF) and inducible nitric oxide synthase (iNOS) expression levels were measured in astrocytes exposed to 6-OHDA, untreated or treated with chokeberry extract. Treatment with chokeberry did not significantly affect the levels of protective proteins HSP70 and BDNF but increased the level of iNOS expression in injured astrocytes, albeit not statistically significantly. This study suggests possible protective effects of chokeberry extract in an in vitro model of PD. The exact mechanism of the protective effect is still unclear and could be the subject of further research.

Little is known about the impairments and pathological changes in the visual system in mild brain trauma, especially repetitive mild traumatic brain injury (mTBI). The goal of this study was to examine and compare the effects of repeated head impacts on the neurodegeneration, axonal integrity, and glial activity in the optic tract (OT), as well as on neuronal preservation, glial responses, and synaptic organization in the lateral geniculate nucleus (LGN) and superior colliculus (SC), in wild-type mice and transgenic animals with overexpression of human TDP-43 mutant protein (TDP-43G348C) at 6 months after repeated closed head traumas. Animals were also assessed in the Barnes maze (BM) task. Neurodegeneration, axonal injury, and gliosis were detected in the OT of the injured animals of both genotypes. In the traumatized mice, myelination of surviving axons was mostly preserved, and the expression of neurofilament light chain was unaffected. Repetitive mTBI did not induce changes in the LGN and the SC, nor did it affect the performance of the BM task in the traumatized wild-type and TDP-43 transgenic mice. Differences in neuropathological and behavioral assessments between the injured wild-type and TDP-43G348C mice were not revealed. Results of the current study suggest that repetitive mTBI was associated with chronic damage and inflammation in the OT in wild-type and TDP-43G348C mice, which were not accompanied with behavioral problems and were not affected by the TDP-43 genotype, while the LGN and the SC remained preserved in the used experimental conditions.

Introduction: Type 2 Diabetes Mellitus (T2DM) is a prevalent cause of morbidity and mortality, particularly due to chronic complications development, most commonly cardiovascular diseases. Among markers for assessment of clinical and subclinical signs of cardiovascular disease, the presence of arteriosclerosis, and stiffening of arterial walls as indicated by the arterial stiffness, was proven to be an important predictor of adverse cardiovascular events. Carotid-femoral pulse wave velocity (PWV) is considered as gold standard for arterial stiffness measurement. On the other side, moderate red wine (RW) consumption was shown to have cardioprotective effects by multiple epidemiologic and experimental studies. Objective: The objective of this study was to examine the effects of moderate daily red wine intake on arterial stiffness and hemodynamic parameters in participants with well controlled T2DM. Subjects and Methods: 18 well controlled-T2DM participants (taking metformin alone or with oral antidiabetic drugs as chronic therapy) were included in the cross-over interventional study during five weeks; the first two weeks being the drive-in period with no alcohol consumption (control), followed by three weeks of moderate, 300 ml per day, consumption of red wine Plavac mali with meals (intervention). At the end of each experimental period we assessed anthropometric data (body mass index), performed biochemical blood analysis (fasting plasma glucose, and HbA1c), while oscillometric and tonometric measurements of arterial stiffness (pulse wave velocity, peripheral and central augmentation indices) and hemodynamic parameters (heart rate, peripheral and central systolic, diastolic and pulse pressure) were performed by Arteriograph and SphygmoCor devices, respectively. Results: Moderate RW consumption in well-controlled T2DM participants induced significant decrease of PWV (7.42±1.44 m/s for control, no alcohol period vs. 6.98±1.44 m/s for intervention, wine consumption period, P=0.013) and peripheral arterial diastolic pressure (79.72±11.47 mmHg in control, no alcohol period vs. 76.39±11.15 mmHg for intervention, wine consumption period, P=0.034), while other arterial stiffness and hemodynamic parameters were not significantly changed although showing a trend of decline. Conclusion: In a cohort of subjects with well controlled T2DM, in whom clinical symptoms of cardiovascular disease were not yet expressed, there was a decrease in PWV. This indicates an improvement in arterial stiffness even after moderate consumption of red wine of relatively short duration., Uvod: Šećerna bolest tipa 2 važan je uzrok obolijevanja i smrtnosti posebice zbog razvoja kroničnih komplikacija od kojih su najčešće kardiovaskularne bolesti. Među markerima za procjenu kliničkih i subkliničkih znakova kardiovaskularnih bolesti, smanjenje arterijske elastičnosti, arterioskleroza, i pojava ukrućivanja stijenke arterija, engl. arterial stiffness, pokazalo se pouzdanim prediktorom kardiovaskularnog rizika. Karotidno-femoralna brzina pulsnog vala smatra se zlatnim standardom procjene arterijske elastičnosti/krutosti. S druge strane, kardioprotektivni učinci umjerene konzumacije crnog vina pokazani su u epidemiološkim i eksperimentalnim istraživanjima. Cilj: Istražiti učinke umjerene konzumacije crnog vina na hemodinamske parametre i parametre arterijske elastičnosti u ispitanika oboljelih od šećerne bolesti tipa 2, kod kojih je bolest dobro nadzirana. Ispitanici i metode: U ukriženo intervencijsko istraživanje uključeno je 18 ispitanika s dobro nadziranom šećernom bolesti tipa 2 (uz kroničnu terapiju metforminom) tijekom pet tjedana: dva tjedna bez konzumacije ikakvih alkoholnih pića, drive-in faza pokusa (kontrolna), nakon kojega je slijedilo tri tjedna umjerene konzumacije crnog vina sorte Plavac mali od 300 ml dnevno uz obrok (intervencija). Na kraju svake faze pokusa ispitanicima su izmjereni antropometrijski parametri (indeks tjelesne mase), učinjena biokemijska analiza krvi (plazmatska koncentracija glukoze natašte i koncentracija HbA1c), a hemodinamski parametri (srčana frekvencija, periferni i središnji sistolički, dijastolički i pulsni tlak) i parametri arterijske elastičnosti (brzina pulsnog vala, periferni i središnji augmentacijski indeksi) određeni su oscilometrijskom (Arteriograph) i tonometrijskom (SphygmoCor) metodom. Rezultati: Nakon umjerene konzumacije vina došlo je do smanjenja brzine pulsnog vala (7,42±1,44 m/s u kontrolnoj fazi pokusa bez konzumacije alkoholnih pića vs. 6,98±1,44 m/s nakon intervencije, P=0,013) i perifernog dijastoličkog tlaka (79,72±11,47 mmHg u kontrolnoj fazi pokusa bez konzumacije alkoholnih pića vs. 76,39±11,15 mmHg nakon intervencije, P=0,034), dok su promjene ostalih hemodinamskih parametara i parametara arterijske elastičnosti bili statistički neznačajne, unatoč ostvarenom trendu smanjena. Zaključci: U kohorti ispitanika s dobro nadziranom šećernom bolesti tipa 2, kod kojih još nisu izraženi klinički simptomi kardiovaskularne bolesti, došlo je do smanjenja brzine pulsnog vala. To ukazuje na poboljšanje arterijske elastičnosti čak i nakon umjerene konzumacije crnog vina relativno kratkog trajanja.

We examined damage and repair processes in the rat cerebellum within the first week following moderate traumatic brain injury (TBI) induced by lateral fluid percussion injury (LFPI) over the left parietal cortex. Rats were killed 1, 3, or 7 days after the injury or sham procedure. Fluoro-Jade B staining revealed 2 phases of neurodegenerative changes in the cell bodies and fibers: first, more focal, 1 day after the LFPI, and second, widespread, starting on post-injury day 3. Purkinje cell loss was detected in posterior lobule IX 1 day following LFPI. Apoptosis was observed in the cerebellar cortex, on days 1 and 7 following LFPI, and was not caspase- or apoptosis-inducing factor (AIF)-mediated. AIF immunostaining indicated axonal damage in the cerebellar white matter tracts 3- and 7-days post-injury. Significant astrocytosis and microgliosis were noticed on day 7 following LFPI at the sites of neuronal damage and loss. Immunohistochemical labeling with the presynaptic markers synaptophysin and growth-associated protein-43 revealed synaptic perturbations already on day 1 that were more pronounced at later time points following LFPI. These results provide new insights into pathophysiological alterations in the cerebellum and their mechanisms following cerebral TBI.

As we are facing worldwide pandemic of COVID-19, we aimed to identify potential pathophysiological mechanisms leading to increased COVID-19 susceptibility and severity in obesity. Special emphasis will be given on increased susceptibility to infections due to obesity-related low-grade chronic inflammation, higher expression of angiotensin converting enzyme-2 and pathway-associated components, as well as decreased vitamin D bioavailability, since all of them provide easier ways for the virus to enter into host cells, replicate and stunt adequate immune responses., Highlights • COVID-19 susceptibility and severity are increased in obesity. • Identifying pathophysiological mechanisms leading to increased COVID-19 susceptibility and severity in obesity is essential. • Emphasis should be given on low-grade chronic inflammation, higher ACE-2 expression and decreased vitamin D bioavailability.

Traumatic brain injury (TBI) is a disabling disorder and a major cause of death and disability in the world. Both single and repetitive traumas affect the brain acutely but can also lead to chronic neurodegenerative changes. Clinical studies have shown some dissimilarities in transactive response DNA binding protein 43 (TDP-43) expression patterns following single versus repetitive TBI. We explored the acute cortical post-traumatic changes of TDP-43 using the lateral fluid percussion injury (LFPI) model of single moderate TBI in adult male mice and investigated the association of TDP-43 with post-traumatic neuroinflammation and synaptic plasticity. In the ipsilateral cortices of animals following LFPI, we found changes in the cytoplasmic and nuclear levels of TDP-43 and the decreased expression of postsynaptic protein 95 within the first 3 d post-injury. Subacute pathological changes of TDP-43 in the hippocampi of animals following LFPI and in mice exposed to repetitive mild TBI (rmTBI) were studied. Changes in the hippocampal TDP-43 expression patterns at 14 d following different brain trauma procedures showed pathological alterations only after single moderate, but not following rmTBI. Hippocampal LFPI-induced TDP-43 pathology was not accompanied by the microglial reaction, contrary to the findings after rmTBI, suggesting that different types of brain trauma may cause diverse pathophysiological changes in the brain, specifically related to the TDP-43 protein as well as to the microglial reaction. Taken together, our findings may contribute to a better understanding of the pathophysiological events following brain trauma.

Introduction: While prescribing biosimilars to patients naive to a biologic treatment is a well- accepted practice, switching clinically stable patients from an originator to a biosimilar is an issue for clinicians. Well designed clinical trials and real-world data which study the consequences of switching from an originator biologic treatment to its biosimilar alternative are limited, especially for monoclonal antibodies. Areas covered: A systematic literature review was conducted on PubMed to identify evidence of the consequences of switching from original biologics to biosimilars. References of included papers were also scrutinized. After a title-, abstract- and full text screening, out of the 153 original hits and 77 additional ones from screening the references, 58 papers (12 empirical papers, 5 systematic reviews and 41 non-empirical papers) were included. Expert opinion: Preventing patients on biologic medicines from switching to biosimilars due to anticipated risks seems to be disproportional compared to the expected cost savings and/or improved patient access. Indeed, it is the opinion of the authors that the concern of switching to biosimilars is overhyped.

Objectives: Self-medication and self-care are of increased global interest among the public, which has been influenced by several factors. Lack of health services, financial constraint, availability, accessibility, extensive advertisement of medicinal products, ignorance, misbelieves, as well as the possibility to treat or manage an illness through self-care are the most relevant. However, OTC drugs used in self-medication process could also cause adverse drug reactions and we aimed to analyze their reports from Croatia in year 2018. Patients and Methods: Overall, 466 medicinal products were registered as OTC drugs in Croatia, and were included in this study. Adverse drug reaction reports of OTC drugs from 1 January to 31 December 2018 were obtained. The following data were analyzed: reporter qualification, patient gender and age, seriousness, active substance name and concomitant therapy. Results: In total 165 adverse drug reactions for OTC drugs were reported in 2018. Most commonly reported generic drugs were ibuprofen, 22 reports (13.3%) and paracetamol, 17 reports (10.2%). Concomitant therapy was reported in 25.3 % of the adverse drug reaction reports. Consumers that experienced adverse drug reaction of OTC drugs were mainly female gender (P=0.05). Out of 47 adverse drug reactions that have been reported for children, 26 of them were accidental exposure to product by child. Pharmacists reported 36.97% of adverse drug reactions and consumers reported 31.52%. Conclusion: Accidental exposure to OTC drugs by child observed in our study could have been prevented and childproofing mechanisms should be communicated to parents., Ciljevi: Samoliječenje i skrb o vlastitom zdravlju ima rastući interes javnosti, pod utjecajem različitih faktora. Nedostatak zdravstvene usluge, financijski utjecaj, dostupnost lijekova te opširno reklamiranje bezreceptnih lijekova su neki od najčešćih faktora koji utječu na popularnost samoliječenja. Međutim, bezreceptni lijekovi koji se koriste u svrhu samoliječenja također uzrokuju nuspojave, a cilj ovog istraživanja bio je analizirati prijave tih nuspojava iz Hrvatske u 2018.Cilj ovog istraživanja bio je analizirati sumnje na nuspojave bezreceptnih lijekova prijavljene u 2018. godini. Pacijenti i metode: Ukupno je 2018. godini na tržištu u Republici Hrvatskoj bilo registrirano 466 lijekova, koji su uključeni u ovo istraživanje. Prijave sumnji na nuspojave bezreceptnih lijekova zaprimljene od 1. siječnja do 31. prosinca 2018. uključene su u ovo istraživanje. Rezultati: Ukupno je prijavljeno 165 sumnji na nuspojave bezreceptnih lijekova u promatranom periodu. Najčešći generički lijekovi uključeni u prijave su ibuprofen s 22 prijave (13,3%) i paracetamol sa 17 prijava (10,2%). Drugi lijekovi u terapiji prijavljeni su u 25,3% slučajeva. Korisnici bezreceptnih lijekova su bili većinom ženskog spola (P=0,05). Od 47 sumnji na nuspojave lijekova prijavljenih u djece, 26 je bilo slučajnih izloženosti lijeka djetetu. Ljekarnici su prijavili 36,97% sumnji na nuspojave, a sami korisnici 31,52%. Zaključak: Slučajna izloženost bezreceptnih lijekova djeci uočena u ovome istraživanju može se prevenirati, mehanizmi za zaštitu djece trebali bi biti objašnjeni pacijentima.

The Committee for Orphan Medicinal Products (COMP) of the European Medicines Agency (EMA) is responsible for evaluating applications for orphan designation (OMPDs) and for deciding the orphan status at the time of marketing authorization of medicines in the European Union (EU). In this review, we provide transparency regarding assessment criteria and an in-depth review of nonclinical models and data that have been used to support OMPDs. Additionally, we present a literature-based analysis of existing nonclinical models and discuss key features of nonclinical studies, which are considered crucial for the support of future OMPDs. This could not only inform future drug development in rare infectious conditions, but also indicate areas where nonclinical models are indispensable or can be made more efficient.

Uvod: Kardiovaskularne bolesti danas su najčešći uzrok smrtnosti diljem svijeta. Svjetska zdravstvena organizacija ulaže velike napore i novac kako bi se, kombinirano promjenom životnih navika i farmakoterapijom, smanjila smrtnost pacijenata i povećala kvaliteta života. Nuspojave na lijekove neizbježna su posljedica njihovog farmakološkog djelovanja. Metode: Provedena je analiza podataka spontano prijavljenih sumnji na nuspojave lijekova koji djeluju na srce i krvožilje (ATK skupina C), zatraženih od Agencije za lijekove i medicinske proizvode (HALMED). Prijave iz 2018. godine su analizirane prema: spolu i dobi pacijenta, prijavitelju, ozbiljnosti, broju lijekova u istodobnoj primjeni te prema klasifikaciji organskih sustava Medicinskog rječnika za regulatorne poslove, MedDRA. Rezultati: U razdoblju od 1. siječnja 2018. do 31. prosinca 2018. u RH je prijavljeno ukupno 767 sumnji na nuspojavu lijekova iz ATK skupine C. Polovica zaprimljenih sumnji na nuspojavu lijeka prijavljena je od strane ljekarnika, a najmanji broj od strane ostalih zdravstvenih djelatnika. Pacijenti koji su sumnjali na nuspojavu lijeka su dominantno bili ženskog spola, a u 50,3 % prijava se radilo o pacijentima starije životne dobi (stariji od 60 godina). Od 133 djelatne tvari registrirane na RH tržištu, za njih 91 je prijavljena barem jedna sumnja na nuspojavu lijeka. Najveći broj prijava zaprimljen je za ramipril, 43 prijave, što čini ukupno 5,6 % od ukupnog broja zaprimljenih sumnji. Pronađena je statistički značajna razlika u broju prijavljenih nuspojava za terapijsku skupinu C09 – lijekove koji djeluju na RAAS, u usporedbi s drugim terapijskim skupinama (P < 0,001). Ova skupina lijekova u 2018. godini činila je gotovo polovicu svih prijavljenih sumnji na nuspojave lijekova iz ATK klasifikacije C. Prema broju prijavljenih sumnji na nuspojave lijekova iz ATK klasifikacije C na drugome mjestu su hipolipemici (statini), a na trećem mjestu su beta blokatori. Ostalih 5 skupina lijekova čine 25 % svih prijavljenih sumnji na nuspojave lijekova. Većina prijavljenih sumnji, 75,5%, nije zadovoljavala kriterije ozbiljnosti te nisu svrstane u ozbiljne nuspojave. Zaključak: Rezultati ovog istraživanja usporedivi su s prethodnim istraživanjima te bi trebali povećati svijest o važnosti prijavljivanja sumnji na nuspojave lijekova., Introduction: Cardiovascular diseases are now the most common cause of death worldwide. World Health Organization invests a massive effort and financial funds to control and reduce the appearance of these conditions, both by suggesting changes in lifestyles and use of pharmacotherapy. Adverse drug reactions are the inevitable consequence of drugs pharmacological action. Methods: We conducted a data analysis of spontaneously reported suspected adverse drug reactions of cardiovascular drugs provided by Agency for Medicinal Products and Medical Devices (HALMED). Reports were analyzed by: gender and age of patients, reporter qualification, seriousness, number of medications in concurrent therapy and by classification. Results: In the period from January 1st 2018 until December 31st 2018 in Republic of Croatia there have been a total of 767 suspected adverse drug reactions of group C (ATC classification). Half of the adverse drug reactions were reported by pharmacist and fewest numbers were reported from other heatlh care professionals. Most of the patients were women and in 50.3% of reports patients were older than 60 years. From 133 active substances registered in Croatian market, 91 had at least one reported adverse drug reaction. The greatest number of reports was received for ramipril, 43 reports, which is 5.6% of total number of received reports. Statistically, there was a significant difference found in number of reported adverse drug reactions of therapeutic class C09 - drugs acting on RAAS in comparison to other therapeutic classes (P < 0.001). This class of drugs in 2018. made almost a half of total reported adverse drug reactions from ATC C classification. According to the number of reported adverse drug reactions from ATC C classification in second place are hypolipemics (statins), and in third place are beta blockers. Other 5 groups combined made 25% of total reported adverse drug reactions. Most of the reported adverse drug reactions, 75.5% of them, did not fulfill the criteria of seriousness and therefore were not classified as serious. Conclusion: Results of the present study are comparable with previous research and should raise awareness of adverse drug reaction reporting practice importance.

Objectives: Hypothyroidism is a very common disorder and refers to all pathological conditions defined by deficiency of hormones thyroxine and triiodothyronine. The total prevalence, according to previously conducted studies, is around 3%, and of undiagnosed hypothyroidism it is 5%. A gold standard in treatment of this disease is levothyroxine. Patients and Methods: Levothyroxine oral tablets marketed in Croatia were studied. Adverse drug reaction reports for levothyroxine obtained from 1 January 2006 to 31 December 2018 were included. The following data were analyzed: year, reporter qualification, patient gender and age, seriousness, concomitant therapy and system organic class according to MedDRA. Results: During period from 2006 to 2018 the total number of levothyroxine adverse drug reaction reports was 146. In year 2018 22.76% of all the reports was obtained. Female gender reported adverse drug reactions predominately, compared to male, 121 vs. 22 reports. In 75.2% of the reports the only involved drug was levothyroxine. Pharmacists most commonly reported adverse drug reactions with 64 reports. Almost 75% of the reports were not classified as serious. Injury, poisoning and procedural complications, General disorders and administration site disorders and Gastrointestinal disorders with 16.9%, 15.3% and 11.2% of the reactions respectively were most commonly reported system organ classes. Conclusion: During the examined period reports of adverse drug reactions for oral tablets of levothyroxine were classified as not serious. Future studies should involve other countries reports and other drug formulations of levothyroxine in order to improve knowledge of levothyroxine safety profile., Ciljevi: Hipotireoza je vrlo čest poremećaj, a odnosi se na sva patološka stanja definirana nedostatkom hormona tiroksina i trijodtironina. Prema prethodno provedenim istraživanjima ukupna učestalost u populaciji iznosi oko 3%, a nedijagnosticirane hipotireoze prema procjenama ima oko 5%. Zlatni standard u liječenju ove bolesti je levotiroksin. Pacijenti i metode: U ovo istraživanje su uključene isključivo tablete za oralnu primjenu levotiroksina koje se nalaze na tržištu u Republici Hrvatskoj. Uključene su sumnje na nuspojave levotiroksina zaprimljene od 1. siječnja 2006. do 31. prosinca 2018. godine. Analizirani su sljedeći podaci: godina prijave, kvalifikacija izvjestitelja, spol i dob pacijenta, ozbiljnost nuspojave, istodobna primjena drugih lijekova u terapiji i organski sustavi prema MedDRA klasifikaciji. Rezultati: Tijekom razdoblja od 2006. do 2018. godine ukupan broj sumnji na levotiroksin bio je 146. U 2018. godini prijavljeno je 22,76% svih sumnji. Ženski spol pretežno je izvijestio o nuspojavama lijekova, u usporedbi s muškim, 121 prema 22 prijave. U 75,2% prijava jedini lijek bio je levotiroksin. Ljekarnici su najčešće prijavljivali, s 64 prijavljene sumnje na nuspojave levotiroksina. Gotovo 75% sumnji nije klasificirano kao ozbiljno. Ozljede, trovanja i proceduralne komplikacije, Opći poremećaji i poremećaji na mjestu primjene te Gastrointestinalni poremećaji sa 16,9%, 15,3% i 11,2% reakcija najčešće su prijavljeni u sistemskim klasama sustava. Zaključak: Tijekom ispitivanog razdoblja sumnje na nuspojave lijekova za levotiroksin nisu klasificirane kao ozbiljne. Buduća istraživanja trebaju uključivati podatke drugih zemalja, a i druge formulacije lijekova levotiroksina, kako bi se poboljšalo znanje o sigurnosnom profilu levotiroksina.

U današnje vrijeme traumatska ozljeda mozga (TBI) jedan je od glavnih socioekonomskih i javnozdravstvenih problema. Zbog svoje velike smrtnosti i brojnih poteškoća nastalih od same ozljede, TBI je potrebno pridati više pažnje. U ovom radu je opisan utjecaj primjene pioglitazona na neurodegeneraciju i ekspresiju mikroglije u parijetalnom korteksu i hipokampusu te utjecaj na ekspresiju ciklooksigenaze-2 (COX-2), inducibilne oksidaze dušikovog oksida (iNOS) i proteina toplinskog šoka 70 (HSP70) u hipokampusu nakon TBI uzrokovane modelom lateralne ozljede tlakom tekućine (LPFI). Pioglitazon je primijenjen u dozi od 1 mg/kg 10 min i 12 h nakon indukcije TBI. Kontrolna grupa štakora je lažno operirana i primijenjeno im je otapalo. Štakori su dekapitirani 24 sata nakon TBI te su parijetalni korteks i hipokampus analizirani biokemijskim i histološkim metodama. Analize su pokazale da nakon TBI nastaju neurodegenerativne promjene u parijetalnom korteksu i dentatnom girusu (DG) hipokampusa, kao i značajna reakcija mikroglije u parijetalnom korteksu i svim ispitivanim dijelovima hipokampusa. U hipokampusu je zabilježena i povećana ekspresija COX-2 i HSP70. Pioglitazon je značajno smanjio broj Iba1 pozitivnih stanica u DG hipokampusa ozlijeđenih životinja, dok na ostale ispitvane parametre nije imao učinka. Ovim radom pokazano je da pioglitazon, primijenjen u dvije doze nakon TBI uzrokovane s LPFI, djeluje na posttraumastku reaktivnu mikrogliozu u određenim moždanim regijama, no točan mehanizam ovog djelovanja nije jasan te su potrebna daljnja istraživanja učinaka ovog lijeka u tretmanu TBI., Today, traumatic brain injury (TBI) is one of the major socio-economic and public health issues. Due to its high mortality and the many difficulties caused by the injury itself, TBI needs more attention. This paper describes the effects of pioglitazone on the neurodegeneration and expression of microglia in the parietal cortex and hippocampus, and the effect on the expression of COX-2, iNOS, and HSP70 in the hippocampus, after TBI caused by lateral fluid pressure injury (LPFI) model. Pioglitazone was administered at a dose of 1 mg/kg 10 min and 12 h after TBI induction. The control group of rats was sham operated and the vehicle was administered instead of the drug. Rats were decapitated 24 hours after TBI and the parietal cortex and hippocampus were analyzed by biochemical and histological methods. Analyzes revealed that after TBI, neurodegeneration occurs in the parietal cortex and dentate gyrus (DG) of the hippocampus, as well as microglia reactions in the parietal cortex and all the tested areas of the hippocampus. Expressions of COX-2 and HSP70 in the hippocampus were significantly higher after brain trauma. Pioglitazone cause a reduction in the number of Iba1 positive cells in the DG hippocampus of the injured animals compared to vehicle-treated, injured rats. This work demonstrates that pioglitazone, administered at two doses after LPFI-induced TBI, can significantly reduce the number of Iba1 positive cells in certain brain regions, but the exact mechanism of this effect is not clear suggesting that further studies on this drug in the treatment of TBI are needed.

Objectives: The aim of the present study was to compare adverse drug reaction reports of metformin and metformin in fixed combination in Croatia from 2007 to 2018. Materials and Methods: The data of adverse drug reaction reports received from 1 January 2007 to 31 December 2018 was analyzed in this retrospective study. Metformin reports were categorized into two main groups: single‐drug formulations and fixed‐dose combinations of drugs. The data of the year of the adverse drug reaction report, reporter qualification, patient age and gender, adverse drug reaction seriousness and other medication in therapy was included. Results: During the examined period the number of the metformin adverse drug reactions reports was 377 (70.3%) and metformin in combinations had 159 (29.7%) reported adverse drug reactions. Overall, this accounts for 536 adverse drug reaction reports included in this study. Majority of all the reports were provided by physicians. Female consumers reported a largest proportion of adverse drug reactions when compared to male consumers. Most of the reports were obtained by elderly, and included concomitant drug in therapy, other than suspected metformin or metformin in combination. Most commonly reported drug combination was metformin and vildagliptin, which were included in 55 of the reports. Majority of the reports, 87.1 %, included adverse drug reaction classified as non-serious and lactic acidosis was reported in 1% of the cases. Conclusion: Metformin was more frequently reported than metformin in combinations during the examined period. However, as the market of hypoglycemic drug combinations will probably rise in the future, the education of all the interested parties should be proposed in order to monitor safety of newly introduced drugs. Ciljevi: Usporediti prijave sumnji na nuspojave lijekova metformina i metformina u fiksnim kombinacijama u Republici Hrvatskoj u razdoblju od 2007. do 2018. Materijali i metode: Podatci o prijavama sumnji na nuspojave lijekova zaprimljeni od 1. siječnja 2007. do 31. prosinca 2018. analizirani su u ovom retrospektivnom istraživanju. Prijave metformina podijeljene su u dvije skupine: metformin i metformin u fiksnim kombinacijama. Podatci o godini prijave, kvalifikaciji prijavitelja, dobi i spolu pacijenta, ozbiljnosti nuspojave i broju ostalih lijekova u terapiji su uključeni u ovo istraživanje. Rezultati: Tijekom ispitnog razdoblja broj sumnji na nuspojave metformina iznosio je 377 (70,3%), a metformin u kombinacijama imao je 159 (29,7%) prijavljenih sumnji na nuspojave. Sveukupno, to čini 536 prijavljenih sumnji na nuspojavu lijekova koje su uključene u ovo istraživanje. Liječnici su prijavili najviše sumnji na nuspojave ovih lijekova. Ženski pacijenti prijavili su više sumnji na nuspojavu lijekova u usporedbi s muškarcima. Većina zaprimjlenih sumnji uključivala je pacijente starije životne dobi koji su koristili druge lijekove u terapiji, izuzev metformina ili metformina u kombinacijama. Najčešće prijavljena kombinacija lijekova bila je kombinacija metformina i vildagliptina za koju je zaprimljeno 55 prijava. Većina prijava, 87,1 %, nije uključivala kriterije ozbiljnosti te nisu kategorizirane kao ozbiljne nuspojave. Laktička acidoza prijavljena je u 1% svih slučajeva sumnji na nuspojave. Zaključak: U promatranom razdoblju je prijavljen veći broj sumnji na nuspojave lijekova za metformin, nego za fiksne kombinacije metformina. Međutim, kako će u budućnosti rasti tržište hipoglikemika potrebna je edukacija svih dionika zdravstvenog sustava kako bi se poboljšalo praćenje sigurnosti novih lijekova.

Cilj istraživanja: Svrha ovog istraživanja bila je utvrditi postojanje zaštitnih učinaka gospine trave na poremećaje funkcije kože izazvane izlaganjem UV zrakama. Ispitanici i metode: Proveden je randomizirani kontrolirani pokus koji se odvijao na Medicinskom fakultetu u Splitu u razdoblju od 1. veljače do 1. svibnja 2019. godine, a koji je obuhvatio 28 zdravih ispitanika bez dijagnosticiranih kožnih bolesti. Ispitivana područja kože bila su na objema podlakticama ispitanika. Korišten je uređaj MPA 6 (Courage+Khazaka, Koln, Njemačka) s tri sonde za mjerenje TEWL (engl. transepidermal waterloss) vrijednosti, vlažnosti kože, eritema te melanina. Doza UV zračenja koja se primjenjivala na podlaktici bila je 3 J/cm². Korištena su dva pripravka od kojih je jedan sadržavao aktivni sastojak (Hypericum perforatum), a drugi je bio placebo. Rezultati: Nisu pronađene statistički značajne razlike u ispitanim parametrima kože (eritem, vlažnost kože, melanin i TEWL) između skupine koja je koristila pripravke gospine trave u odnosu na placebo skupinu. Zaključci: Naše istraživanje pokazalo je da gospina trava nema zaštitnih učinaka na poremećaje funkcije kože izazvane izlaganjem UV zrakama te da je potrebno u budućnosti provesti više istraživanja na ovu temu., Aim of the study: The purpose of this study was to determine the presence of protective effects of Hypericum perforatum on skin function disorders caused by exposure to UV rays. Subjects and Methods: A randomized controlled trial was conducted at the Medical School in Split during the period from 1st of February until 1st of May 2019, which included 28 healthy subjects without diagnosed skin diseases. The examined areas of the skin were on both forearms of the examinees. A MPA 6 (Courage + Khazaka, Koln, Germany) device was used with three probes for measuring the TEWL (transepidermal waterloss) value, skin moisture, erythema and melanin. The UV radiation dose applied to the forearm was 3 J / cm². Two preparations were used, one containing the active ingredient (Hypericum perforatum), the other being the placebo. Results: No statistically significant differences were found in the tested skin parameters (erythema, skin moisture, melanin and TEWL) between group that used Saint John`s Wort formulation in comparison with the placebo group. Conclusions: Our research has shown that Saint John`s Wort has no protective effects on skin function disorders caused by the exposure to UV radiation and that there is a need for further research in the future on this topic.

Cilj: Cilj ovog istraživanja bila je procjena znanja i stavova o propisivanju lijekova studenata studijskih programa Medicine i Dentalne medicine Medicinskog fakulteta Sveučilišta u Splitu. Materijali i metode: U ovom radu napravljeno je istraživanje metodom upitnika. Upitnik je bio u potpunosti anoniman i podijeljen je studentima studijskih programa Medicine i Dentalne medicine Medicinskog fakulteta Sveučilišta u Splitu koji su pohađali nastavu kroz travanj i svibanj 2019. godine. U istraživanju je sudjelovalo 597 studenata. Podaci su obrađeni u programu Microsoft Office Excel 2016 i JASP 0.9.2.0. Napravljena je deskriptivna analiza uzoraka, a rezultati su prikazani u postocima. Prikazan je medijan i raspon ili srednja vrijednost ± standardna devijacija (SD) za kontinuirane varijable. Za svaki ishod izračunati su postotci odgovora. Neparametrijski χ 2 test je korišten za procjenu razlike između skupina i korelaciju između varijabli. Rezultati: Ukupno 51.1% studenata smatra da je bol najčešći uzrok propisivanja lijekova u stomatološkoj praksi. 53.9% studenata medicine i 67.4% studenata dentalne medicine smatra da je najčešće propisivani NSAID ibuprofen. Ukupno 49.9% studenata je odgovorilo da su najčešći izvor informacija o propisivanju lijekova udžbenici za propisivanje lijekova. 53.4% studenata medicine i 58.8% studenata dentalne medicine smatra da se lijekovi trebaju propisivati prema njihovom generičkom imenu. Zaključak: Istraživanje je pokazalo da studenti medicine i studenti dentalne medicine imaju slično znanje o propisivanju lijekova. Znanje o propisivanju lijekova od najveće je važnosti za dobru liječničku i stomatološku praksu. Nedovoljno znanje rezultira nepravilnim korištenjem uobičajenih lijekova što sa sobom nosi niz posljedica. Stoga je bitna kontinuirana edukacija o farmakološkoj terapiji kao i o racionalnom propisivanju lijekova tijekom, ali i po završetku studija. Također, potrebno je imati smjernice po kojima će liječnici i doktori dentalne medicine moći kvalitetno dati terapiju i izbjeći mogućnost pogreške vezane za propisivanje lijekova., Objectives: The aim of this study was to assess knowledge and attitudes of medical students and students of dental medicine at the University of Split School of Medicine towards prescribing of drugs. Materials and methods: In this study we assed students' knowledge an attitudes towards prescribing of drugs, using the questionnaire. The questionnaire was fully anonymous and distributed to medical students and students of dental medicine at the University of Split School of Medicine who attended classes from April to May, 2019. The total number of the students who participated in the research was 597. The data were analyzed using Microsoft Office Excel 2016 and JASP 0.9.2.0. Descriptive analysis was performed, and the results are presented in percentages, and median or mean ± standard deviation (SD) for continuous variables. Non-parametric χ 2 test was used to estimate the difference between the groups and the correlation between the variables. Results: A total of 51.1% of students believed that pain was the main cause of drug prescribing in dental practice. 53.9% of medical students and 67.4% of dental students believed that the most commonly prescribed NSAID was ibuprofen. A total of 49.9% of students answered that the most common source of information on prescribing medicines was prescription books. 53.4% of medical students and 58.8% of dental students think that medicines should be prescribed according to their generic name. Conclusion: The research has shown that medical and dental students have similar knowledge of prescribing drugs. Knowledge of prescribing drugs is of utmost importance for good medical and dental practice. Inadequate knowledge results in improper use of common medicines that can lead to a number of negative consequences. Therefore, continuing training on pharmacological therapy as well as on the rational prescribing of medicines during and after the study is essential. It is also necessary to have good guidelines that will allow physicians and doctors of dental medicine to provide quality therapy and avoid the possibility of prescribing errors.

Biološki učinci bijelih, a napose maceriranih bijelih vina jantarne boje i bogatog polifenolnog sadržaja, rijetko su istraživani. Stoga smo u ovom istraživanju ispitali i usporedili učinke standardnog i maceriranog bijelog vina na prirast tjelesne mase štakora te njihovu antioksidacijsku i vazodilatacijsku aktivnost in vitro. Prirast tjelesne mase ispitivan je u mlađih, brzo-rastućih, i starijih štakora koji su dosegli plato svoje težine. Štakori obje dobne skupine koji konzumiraju vino unose manje hrane i imaju manji prirast tjelesne mase u odnosu na štakore koji konzumiraju samo vodu. Ukupni je energetski unos najmanji u štakora koji konzumiraju macerirano vino. U usporedbi s intaktnim, macerirano je vino bolji antioksidans, što je potvrđeno primjenom više metoda utemeljenih na različitim mehanizmima, i bolji izravni vazodilatator noradrenalinom prekontrahiranih aortnih prstenova štakora. Međutim, macerirana vina, proizvedena bez konzervansa, podložna su oksidaciji. Stoga smo dodatno istražili utjecaj oksidacije povezane s izlaganjem maceriranog vina zraku do 48h na njegov kemijski sastav i in vitro biološke učinke. Unatoč 'smeđenju', kemijski sastav oksidiranih vina nije se značajno promijenio u odnosu na intaktno, a antioksidacijski i maksimalni vazodilatacijski učinci ostali su očuvani. Međutim, pri najnižim koncentracijama, kod ograničene raspoloživosti vazoaktivnih fenola, oksidirana macerirana vina ostvarila su, razmjerno duljini izloženosti zraku, slabiju vazodilataciju., Biological effects of white, and particularly amber-colored macerated white wines rich in polyphenolic content, are rarely investigated. Therefore, in this study, we examined and compared the effects of standard and macerated white wine on rats weight gain and their in vitro antioxidative and vasodilating activity. Body weight gain was studied in younger, fastgrowing, and older rats that almost reached their weight plateau. In both age categories, winedrinking animals consumed less food and gained less weight in comparison to water-only drinking controls. Total energy intake was the lowest in macerated wine-drinking rats. In comparison to standard, macerated wine was better antioxidant, as confirmed by several methods based on different mechanisms, and more effective direct vasodilator of noradrenaline-precontracted rat aortic rings. However, macerated wine produced without preservatives is highly susceptible to oxidation. Therefore, we additionally investigated the effects of oxidation associated with its exposure to air for up to 48h on its chemical composition and in vitro biological activities. Despite 'browning', chemical composition of oxidized wines did not change significantly in comparison to intact, and their antioxidant and maximal vasodilatory effects remained preserved. However, at low concentrations, when availability of vasoactive phenols was limited, vasodilatory potency increasingly weakened with exposure to air.

Uporaba duhana, odnosno pušenje predstavlja jednu od ozbiljnijih vrsta ovisnosti današnjice, te je ujedno i među vodećim uzrocima smrtnosti. Duhanski dim sadrži više od 4000 spojeva, od kojih su najopasniji nikotin, katran i ugljični monoksid. Iako sve tvari u dimu utječu na izložene ljude do određenog stupnja, nikotin se općenito smatra primarnom tvari koja je odgovorna za farmakološke reakcije na pušenje, a ponajviše za izazivanje ovisnosti. U mnogim zemljama pušenje duhana je prepoznato kao ozbiljan i opasan zdravstveni problem i glavni faktor koji doprinosi smrtnosti zbog niza bolesti koje se pojavljuju kao posljedica dugotrajnog uživanja u pušenju. Adolescenti su skloni raznim vrstama eksprementiranja što uključuje i isprobavanje novih sredstava ovisnosti, uključujući i pušenje. Kako bi se povećala svijest o štetnosti pušenja, potrebno je educirati ciljne skupine kako bi se prevenirali mogući štetni učinci. Prema podacima brojnih istraživanja koja su provedena o štetnosti pušenja, broj pušača se ne smanjuje u očekivanoj mjeri. U ovom je radu istražena učestalost pušenja kod adolescenata, udio pušača po spolu te sve praćene neželjene posljedice pušenja. U istraživanju je sudjelovao 131 ispitanik u dobi od 13 do 25 godina, a odgovori su analizirani na temelju anketnog upitnika koji je ispunjen od strane učenika i studenata. Dobiveni rezultati pokazuju kako 45% ispitanih osoba puši cigarete, dok je početak pušenja kod 54,2% ispitanika evidentiran tijekom srednje škole, što zapravo i predstavlja najkritičnije razdoblje adolescentne dobi. Iako su učenici i studenti pokazali da su svjesni štetnosti pušenja za njih i njihovu okolinu te da planiraju u budućnosti prestati s tom navikom, ipak se mnogi od njih ne smatraju ovisnima i ne gledaju na to kao na neki problem., Consuming tobacco, i.e. smoking is considered to be one of the most serious addictions nowadays, as well as one of the leading causes of mortality. Tobacco smoke contains more than 4 000 chemicals, among which the most dangerous are nicotine, tar and carbon monoxide. Although all of the smoke chemicals have effect on people to an extent, nicotine is considered to be the primary substance responsible for causing pharmacological reactions, especially addiction. Many countries have recognized smoking as a serious and dangerous health problem and main factor that contributes to mortality rate due to the wide range of diseases that it causes. The adolescents are likely to try out new thing and are prone to experiment with various addictive substances, smoking included. In order to raise awareness and prevent side effects caused by smoking, targeted groups need to be constantly educated. According to the conducted research on the side effects of smoking, the number of smokers is not dropping down to an expected rate. This thesis explores the frequency of smoking among the adolescents, distribution of smoking rate among females and males and side effects of smoking. The research carried out for this thesis included 131 participants, all aged between 13 and 25 years. The responses were collected through the questionnaire filled by the participants. The results revealed that 45% of participants declare themselves as smokers. Among those 45%, 54.2% participants said they started smoking when in high school which is the most critical period of the adolescence. Although the participants revealed that they are aware of smoking side effects (the one affecting themselves, as well those affecting their surroundings) and that they plan to quit in the future, many of the participants do not see themselves as addicts and do not think of smoking as a problem.

Prehrana sportaša, uz naporne treninge, jedan je od osnovnih čimbenika koji utječu na sportske rezultate. Sportaši uz sve intenzivnije i jače treninge imaju veće potrebe za energijom i sve manje vremena za oporavak organizma zbog čega često konzumiraju razne dodatke prehrani kako bi lakše i brže postigli željeni cilj. S obzirom da su postavljeni ciljevi u sportu svakim danom sve veći, sportaši uz dodatke prehrani često konzumiraju i razne lijekove za koje misle da će im poboljšati sportske izvedbe, ne razmišljajući kakve posljedice i neželjene učinke konzumacija takvih sredstava može imati na organizam. Najčešći dodaci prehrani koje sportaši koriste su vitamini, od kojih najviše vitamini B – kompleksa, vitamin C, vitamin D i vitamin E te minerali kalcij, magnezij i željezo; proteinski suplementi, BCAA (branched – chain amino acids) ili aminokiseline razgranatog lanca; L – karnitin te kreatin. Od lijekova, sportaši najčešće posežu za anaboličkim steroidima, testosteronom te hormonom rasta. U ovom radu istražena je učestalost konzumacije dodataka prehrani i lijekova kod 70 ispitanih sportaša, koje koriste najčešće, koliko ih je imalo neželjene učinke te koji su neželjeni učinci koje uzrokuju određeni dodaci prehrani i lijekovi. Od 70 ispitanih, 16 osoba je ženskog, a 54 osobe su muškog spola te se njih 49 izjasnilo da koristi neke dodatke prehrani i/ili lijekove. 32 osobe primjetile su neželjene učinke od kojih je najviše bilo osoba s probavnim tegobama, dermatološkim problemima, povišenim krvnim tlakom te poremećajima u radu srca., Athletes' nutrition, along with hard training, is one of the basic factors that affect the sports results. Athletes with ever more intense and stronger training have greater energy needs and less time for body regeneration, which is why they often consume various nutritional supplements in order to achieve the desired goal more easily and quickly. Since sports goals are set higher every day, athletes often consume various medications along with nutritional supplements because they think medications will improve their sports performance, without thinking of the consequences and side effects of consuming such products. The most common nutritional supplements that athletes use are vitamins, most of which vitamin B complexes, vitamin C, vitamin D and vitamin E, and calcium, magnesium and iron minerals; protein supplements, branched-chain amino acids (BCAAs) or branched chain amino acids; L - Carnitine and Creatine. When it comes to drugs, athletes usually come up with anabolic steroids, testosterone and growth hormone. In this thesis reserched the frequency of dietary supplements and medicines consumption on athletes. The research included 70 athletes and answeres which are the most commonly used supplements, their side effects, and the side effects of certain nutritional supplements and medications. Out of the 70 surveyed, 16 were female and 54 were male and 49 of them opted to use some dietary supplements and / or medicines. Thirty-two people noted the side effects, most of which were people with digestive problems, dermatological problems, hypertension, and heart failure disorders.

Contains fulltext : 193452.pdf (Publisher’s version ) (Open Access) Background: This study was conducted as part of the Driving Reinvestment in Research and Development and Responsible Antibiotic Use (DRIVE-AB) project and aimed to develop generic quality indicators (QIs) for responsible antibiotic use in the inpatient setting. Methods: A RAND-modified Delphi method was applied. First, QIs were identified by a systematic review. A complementary search was performed on web sites of relevant organizations. Duplicates were removed and disease and patient-specific QIs were combined into generic indicators. The relevance of these QIs was appraised by a multidisciplinary international stakeholder panel through two questionnaires and an in-between consensus meeting. Results: The systematic review retrieved 70 potential generic QIs. The QIs were appraised by 25 international stakeholders with diverse backgrounds (medical community, public health, patients, antibiotic research and development, regulators, governments). Ultimately, 51 QIs were selected in consensus. QIs with the highest relevance score included: (i) an antibiotic plan should be documented in the medical record at the start of the antibiotic treatment; (ii) the results of bacteriological susceptibility testing should be documented in the medical record; (iii) the local guidelines should correspond to the national guidelines but should be adapted based on local resistance patterns; (iv) an antibiotic stewardship programme should be in place at the healthcare facility; and (v) allergy status should be taken into account when antibiotics are prescribed. Conclusions: This systematic and stepwise method combining evidence from literature and stakeholder opinion led to multidisciplinary international consensus on generic inpatient QIs that can be used globally to assess the quality of antibiotic use.

We surveyed European medical schools regarding teaching of prudent antibiotic prescribing in the undergraduate curriculum. We performed a cross-sectional survey in 13 European countries (Belgium, Croatia, Denmark, France, Germany, Italy, Netherlands, Norway, Serbia, Slovenia, Spain, Switzerland, United Kingdom) in 2013. Proportional sampling was used, resulting in the selection of two to four medical schools per country. A standardized questionnaire based on literature review and validated by a panel of experts was sent to lecturers in infectious diseases, medical microbiology and clinical pharmacology. In-depth interviews were conducted with four lecturers. Thirty-five of 37 medical schools were included in the study. Prudent antibiotic use principles were taught in all but one medical school, but only four of 13 countries had a national programme. Interactive teaching formats were used less frequently than passive formats. The teaching was mandatory for 53% of the courses and started before clinical training in 71%. We observed wide variations in exposure of students to important principles of prudent antibiotic use among countries and within the same country. Some major principles were poorly covered (e.g. reassessment and duration of antibiotic therapy, communication skills). Whereas 77% of the respondents fully agreed that the teaching of these principles should be prioritized, lack of time, mainly due to rigid curriculum policies, was the main reported barrier to implementation. Given the study design, these are probably optimistic results. Teaching of prudent antibiotic prescribing principles should be improved. National and European programmes for development of specific learning outcomes or competencies are urgently needed. Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved

Cilj: Cilj ovog istraživanja je procijeniti znanja i stavove studenata medicine, medicine na engleskom jeziku, dentalne medicine i farmacije Medicinskog fakulteta Sveučilišta u Splitu prema uporabi antibiotika i rezistenciji na antibiotike te usporediti stavove i znanja studenata određenog studija od prve do zadnje godine, te drugih studija. Materijali i metode: U ovom radu napravljeno je transverzalno istraživanje, metodom upitnika. Upitnik je bio u potpunosti anoniman i podijeljen je svim studentima Medicinskog fakulteta Sveučilišta u Splitu koji su pohađali nastavu kroz travanj i svibanj 2018. godine. U istraživanju je sudjelovalo 947 studenata. Studentima je u anketi naveden cilj istraživanja, te su traženi u prvom dijelu opći podaci, a u drugom stavovi i znanja o uzimanju antibiotika i rezistenciji na antibiotike. Podaci su obrađeni u programu Microsoft Office Excel 2016. Napravljena je deskriptivna analiza uzoraka, a rezultati su prikazani u postocima za dihotomne varijable, te medijan ili srednja vrijednost ± standardna devijacija (SD) za kontinuirane varijable. Rezultati: U istraživanju je sudjelovalo 947 studenata, od ukupno 1107 upisanih (85,6 %). Kad je u pitanju znanje, trećina studenata dentalne medicine, četvrtina studenata medicine i farmacije smatra da je paracetamol antibiotik za smanjenje boli. Međutim, ovaj postotak se značajno smanjuje od prve do apsolventske godine na svim studijima. Od studenata 6. godine medicine, njih 18 % koristi ostatke antibiotika u slučaju povratka bolesti, a postotak je i veći na studiju medicine na engleskom jeziku, gdje 24 % studenata završne godine pokazuje ovakvo ponašanje. Iako su studenti naveli da poznaju smjernice, svega 23 % studenata na koncu 6. godine medicine može navesti ispravnu smjernicu, a na engleskom studiju niti jedan student zadnje godine studija. Na dentalnoj medicini sedam studenata na cijelom studijskom programu je imenovalo neku konkretnu smjernicu. Studenti farmacije su se pokazali najupućenijima, pošto je 76 % na posljednjoj studijskoj godini imenovalo ISKRA smjernice. Zaključak: U ovom radu pokazali smo da, iako imaju teorijsko znanje, studenti medicine, medicine na engleskom jeziku, dentalne medicine i farmacije ne ponašaju se uvijek u skladu s naučenim, kad je u pitanju ispravno korištenje antibiotika. Također, studenti su pokazali loše znanje po pitanju korištenja smjernica, te bi se svakako savjetovalo uvođenje, ako ne cijelog kolegija, barem neke vrste edukacije u sklopu predmeta na višim godinama studija. Objectives: The aim of this study was to assess the knowledge and attitudes of medical students in Croatian and English programme, students of dental medicine and pharmacy at the University of Split School of Medicine toward the use of the antibiotics and the resistance to the antibiotics; to compare the attitudes and knowledge of the students at the particular study from the first to the last year, and the other studies. Materials and methods: In this study, a transversal survey was conducted using the questionnaire. The questionnaire was fully anonymous and distributed to all students who attended classes from the April to the May 2018. The total number of the students who participated in the research was 947. In the first part of the questionnaire students were asked for general information. In second part they answered about their attitutes and knowledge on taking antibiotics and resistance to antibiotics. Descriptive sample analysis was performed, and the results are presented in the percentage for the dichotomous variables, and the median or mean ± standard deviation (SD) for the continuous variables. Results: The study involved 947 students, out of a total of 1107 enrolled (85,6 %). A third of dental students, and a quarter of medical and pharmacy students believe that paracetamol is an antibiotic that reduces pain. However, this percentage is significantly decreased from the first to the final years in all studies. 18 % of students in the 6th year of medicine use antibiotic residues in the event of a disease return, and the percentage is even higher, 24 %, for medicial studies in english students. Only 23 % of students at the end of the 6th year of medicine could indicate the correct guidelines, and none in the English programme. Seven students of dental medicine have named a specific guidelines in the entire study program. Pharmacy students were the most informed, since 76 % of the last year of the study programme have named ISKRA guidelines. Conclusion: Although the students have theoretical knowledge, they do not always behave according to what they learned when it comes to proper use of antibiotics. Students have shown inadequate knowledge of the use of guidelines. Therefore, continous education on this topic is needed, at least more information at the higher years of the studies.

Generation of amyloid-β peptides (Aβs) by proteolytic cleavage of the amyloid-β protein precursor (AβPP), especially increased production of Aβ(42)/Aβ(43) over Aβ(40), and their aggregation as oligomers and plaques, represent a characteristic feature of Alzheimer’s disease (AD). In familial AD (FAD), altered Aβ production originates from specific mutations of AβPP or presenilins 1/2 (PS1/PS2), the catalytic subunits of γ-secretase. In sporadic AD, the origin of altered production of Aβs remains unknown. We hypothesize that the ‘human chemical exposome’ contains products able to favor the production of Aβ(42)/Aβ(43) over and shorter Aβs. To detect such products, we screened a library of 3500 + compounds in a cell-based assay for enhanced Aβ(42)/Aβ(43) production. Nine pyrazole insecticides were found to induce a β- and γ-secretase-dependent, 3–10-fold increase in the production of extracellular Aβ(42) in various cell lines and neurons differentiated from induced pluripotent stem cells derived from healthy and FAD patients. Immunoprecipitation/mass spectrometry analyses showed increased production of Aβs cleaved at positions 42/43, and reduced production of peptides cleaved at positions 38 and shorter. Strongly supporting a direct effect on γ-secretase activity, pyrazoles shifted the cleavage pattern of another γ-secretase substrate, alcadeinα, and shifted the cleavage of AβPP by highly purified γ-secretase toward Aβ(42)/Aβ(43). Focusing on fipronil, we showed that some of its metabolites, in particular the persistent fipronil sulfone, also favor the production of Aβ(42)/Aβ(43) in both cell-based and cell-free systems. Fipronil administered orally to mice and rats is known to be metabolized rapidly, mostly to fipronil sulfone, which stably accumulates in adipose tissue and brain. In conclusion, several widely used pyrazole insecticides enhance the production of toxic, aggregation prone Aβ(42)/Aβ(43) peptides, suggesting the possible existence of environmental “Alzheimerogens” which may contribute to the initiation and propagation of the amyloidogenic process in sporadic AD.

Screening tools for detecting potentially inappropriate medications (PIMs) represent an important way to assess drug prescribing in the elderly. Recently, we introduced a new comprehensive tool to detect both PIMs and clinically important drug-drug interactions (DDI). The aim of the study was to assess the applicability of the new tool. The new tool was used to detect PIMs and DDI and to assess their relation to morbidity and hospital admissions. It was also compared to the widely used Beers criteria. The study population included 454 consecutive patients aged ≥65 years who were acutely admitted to the Department of Internal Medicine of the University Hospital of Osijek. The Naranjo protocol was used to analyze the causal relationship between a drug and an adverse event. According to the new protocol, 44 % patients were taking PIMs, while 33 % patients were taking drugs with potentially serious DDIs. In 11 % of the overall number of patients, the cause of admission was adverse drug reaction (ADR), and among contributing drugs, 44 % were potentially inappropriate according to our protocol. Gastrointestinal bleeding was the most common diagnosis causing ADR-associated admission, and in 72 % cases, either PIM or a potentially serious DDI was involved. The new Croatian tool detected a high number of patients taking PIMs and/or having potentially important drug-drug interactions. The tool also detected almost half of the drugs contributing to ADR-associated admission. We expect the tool to be useful in prescription evaluation for the elderly inpatient and outpatient population.

Recombinant human erythropoietin (rhEpo) is a multi-functional drug with antioxidant potential. However, the underlying molecular mechanisms of its action are still unclear. The purpose of this study was to investigate the effects of rhEpo on the brain infarct volume as well as on the levels of the neuronal damage, oxidative stress parameters and active caspase- 3, nuclear factor erythroid 2-related factor 2 (Nrf2) and haemeoxygenase-1 (HO-1) expressions in the hippocampi of rats exposed to the right middle cerebral artery occlusion (MCAO) for 1 hr. Ischaemic animals received either vehicle or rhEpo (5000 IU/kg, i.p.) immediately or 3 hr after the induction of ischaemia. Sham- operated, vehicle-treated animals served as the control group.Rats were killed 24 hr after the onset of the ischaemic or sham experimental procedure. MCAO caused ipsilateral brain infarction within the striatum and cortex. In the CA1 region of the hippocampi, we did not find significant neuronal loss, but a statistically significant rise in the active caspase-3 and Nrf2 protein expressions was registered. We detected also significant increases in the hippocampal levels of oxidative stress parameters (thiobarbituric acid-reactive substances, superoxide dismutase, glutathione peroxidase). Post-ischaemic administration of rhEpo significantly reduced the brain infarct volume, decreased levels of all tested oxidative stress parameters and increased the Nrf2 expression level. These findings suggest that decrease in oxidative stress parameters in the hippocampus could be an early indicator of post-ischaemic neuroprotective effect of rhEpo in rats exposed to focal cerebral ischaemia and that this effect could be attributable to additional post-ischaemic activation of Nrf2 endogenous antioxidant system.

Uporaba prehrambenih aditiva u posljednjih tridesetak godina je u značajnom porastu. Posljedično, sve je veća zabrinutost zbog neželjenih učinaka na zdravlje ljudi. Neželjeni učinak je svaki štetni, abnormalni učinak na organizam koji uzrokuje anatomsko ili funkcionalno oštećenje, ireverzibilne fizičke promjene ili povećava osjetljivost na druge biološke, kemijske ili okolišne čimbenike. Najčešći neželjeni učinci izazvani prehrambenim aditivima su hipersenzibilnost i kancerogenost. Prehrambeni aditivi su tvari koje se dodaju hrani kako bi se poboljšala svojstva hrane, a da joj se pritom ne mijenja hranjiva vrijednost. S obzirom da je danas nezamislivo proizvesti hranu bez uporabe prehrambenih aditiva, nadležna tijela brinu o sigurnosti prehrambenih aditiva koji se nalaze na tržištu. U ovom diplomskom radu, učinjena je analiza neželjenih učinaka najčešće korištenih aditiva u prehrambenoj industriji. The use of food additives in the last thirty years is significantly increasing. Consequently, there is growing concern due to adverse effects on human health. Adverse effect is any harmful, abnormal effect on the organism that causes anatomic or functional damage, irreversibile physical changes or increases sensitivity other biological, chemical or enviromental factors. The most common adverse effects caused by food additives are hypersensitivity and carcinogenicity. Food additives are substances added to food to enhance the characteristics of food without changing its nutritional value. Since it is unthinkable today to produce food without the use of food additives, the competent authorities worry about the safety of food additives that are on the market. In this graduation thesis, analysis was conducted of adverse effects of the most commonly used additives in the food industry.

Naslov: Izravni vazodilatacijski i in vitro antioksidacijski učinci vina i prošeka Cilj istraživanja: Ispitati i usporediti fenolni sadržaj i biološke učinke vina i prošeka proizvedenih od iste sorte grožđa. Materijali i metode: Za potrebe istraživanja upotrijebljena su 24 štakora soja Sprague - Dawley, mužjaka, stari 3-5mjeseci, tjelesne mase 300-450 g, uzgojenih u Sveučilišnoj nastambi za pokusne životinje Medicinskog fakulteta u Splitu. U istraživanju sukorištena eksperimentalna vina (Plavac mali), bijela vina (Pošip) te prošeci od istih sorti grožđa. Nakon određivanja glavnih fenolnih frakcija (flavonoida i ne-flavonoida), ispitan je izravni vazodilatacijski učinak odabranih vina na izoliranim prstenovima aorte štakora. Kumulativnoj dozi (0,5 do 5‰) pojedinačnog ispitivanog vina bili su izloženi isključivo prstenovi s očuvanim endotelom (acetilkolinska relaksacija veća od 60% nakon prethodne prekontrahiranosti noradrenalinom). Relaksacija vaskularnih prstenova potaknuta određenom dozom vina se izražavala kao postotak smanjenja vazokonstrikcije uzrokovane noradrenalinom. Koncentracije ukupnih fenola, flavonoida i antocijana, kao i antioksidacijski kapacitet svih ispitivanih uzoraka određeni su spektrofotometrijskim metodama. Antioksidacijski kapacitet određen je FRAP (prema engl. Ferric reducing antioxidant power) metodom i izražen u mmol/L ekvivalenata troloksa (TE). Koncentracija pojedinačnih polifenolnih spojeva, određena je primjenom tekućinske kromatografije visoke djelotvornosti, HPLC. Rezultati: Izravni maksimalni vazodilatacijski učinak, Emax, crnog i bijelog prošeka u usporedbi sa standardnim crnim i bijelim vinom bio je 20-30% manji s vrijednostima 60,4±3,9%, 64,4±6,0% i 64,7±6,1% vs. 87,1%±5,0% za crni prošek iz 2007., 2008. i 2009.godine vs. crno vino iz 2007.godine te Emax 12,9±3,1% vs. 21±4,9% za bijeli prošek iz 2008. godine vs. bijelo vino iz 2010.godine. Antioksidacijska sposobnost crnog prošeka također pokazuje niže vrijednosti u usporedbi sa vinom iste sorte u sva tri uzorka, dok bijelo vino i prošek pokazuju slične vrijednosti koje su međutim zanemarivo niske. Crno se vino odlikuje visokim sadržajem ukupnih polifenola, flavonoida i antocijana, dok je u crnom prošeku koncentacija ukupnih fenola za oko trećinu manja, antocijana ista, a ne-flavonoida trostruko veća. Bijelo vino i prošek imaju mnogo niži sadržaj antocijana i ukupnih fenola uz izraženu dominaciju ne-flavonoidne komponente. Zaključak: Studija je pokazala da prošek crne sorte ima značajnu, ali ipak slabiju vazodilatacijsku i antioksidacijsku aktivnost in vitro, da je vrlo bogat polifenolima, ali da ima manju koncentraciju ukupnih fenola i flavonoida, a veću koncentracijom ne-flavonoida u usporedbi sa standardnim crnim vinom (Plavac mali). Vino i prošek dobiveni od bijele sorte grožđa ostvarili su slabi vazodilatacijski i antioksidacijski učinak in vitro, iako je vino bilo potentnije u ostvarivanju vazodilatacijskog učinka. Odlikuju se niskim koncentracijama i antocijana i ukupnih fenola te dominacijom ne-flavonoida. Uspoređujući polifenolni sadržaj i sastav, može se zaključiti da tradicionalni način proizvodnje prošeka u usporedbi sa standardnim tehnikama proizvodnje vina dovodi do povećanja koncentracije određenih ne-flavonoidnih i flavonoidnih spojeva, koji međutim ne doprinose značajno vazodilatacijskom i antioksidacijskom učinku., Title: Vasodilatory and antioxidant activity of Prosek dessert wine in comparison to standard wine Keywords: red wine, wine polyphenols, vasodilation, antioxidant activity, rat aorta Objective: Dessert wine Prosek is produced in accordance with the principles of traditional wine making method by fermentation of dried grapes. It results with wine of distinctive organoleptic properties, high alcohols and unfermented sugars. In comparison with standard wines, biological effects of dessert wines are largely uninvestigated. Our aim was to analyze and compare biochemical, antioxidant and direct vasodilatory activity of Prosek produced from the most important red autochthonous Croatian variety Plavac mali with the corresponding standard red wine and Prosek produced from white variety Pošip with the standard white wine. Materials and methods: Three vintages of Prosek Plavac mali (2007, 2008 and 2009) were compared with wine Plavac mali from 2007 and one vintage of Prosek Pošip from 2008. with wine Pošip from 2010. All tested wines were analyzed spectrophotometrically for the content of total phenolics, flavonoids, non-flavonoids and anthocyanins and by HPLC for the content of selected flavanols and phenolic acids. The antioxidant activity was determined by Ferric Reducing Antioxidant Power (FRAP). The vasodilatory activity of wines was determined in the isolated rat aortic rings (N=24 rats) precontacted by norepinephrine (10-7 M). Wines were applied in cumulative concentrations from 1:10000 to 5:1000. Results: The direct maximal vasodilatory effect of red Prosek (Plavac mali) relative to the standard red wine was 20 - 30% lower with Emax of 60,4±3,9%, 64,4±6,0%, 67,5 ±6,1% and 87,1%±5% for Prosek from 2007, 2008, 2009 and wine from 2007, respectively. Maximal vasodilatory effects of white Prosek (Pošip ) relative to the standard white wine was also lower with Emax 12,9±3,1% and 21,6±4,9% for Prosek from 2008 and wine from 2010, respectively. Antioxidant activity of red Prosek was also consistently lower in all three measurement systems in comparison to red wine. White Prosek and white wine showed similar ability to reduce the ferric ion, but the values of their antioxidant activity were negligible low. The total phenolic and flavonoid content was higher in red wine, whereas red wine and Prosek samples were similar in anthocyanins content. On the other hand, Prosek had three-fold higher content of non-flavonoids. Conclusions: Prosek produced from red and white variety proved inferior to standard red and white wine in direct vasodilatory and antioxidant activity. Traditional Prosek wine making technique resulted in higher content of special flavonoid and non-flavonoid compounds which were not related to vasodilatory and antioxidant activity of wine.

Na europskom tržištu može se naći sve više novih psihoaktivnih tvari koje oponašaju učinak kontroliranih droga. Sintetski kanabinoidi i sintetski katinoni zajedno čine gotovo dvije trećine novih droga. Prodaju se kao pravna zamjena za marihuanu i stimulanse. Iako sadrže oznaku kako nisu za ljudsku upotrebu, stopa zloupotrebe u svijetu naglo raste, osobito među adolescentima. Sintetski kanabinoidi pojavljuju se kao biljne mješavine, prah ili smola. Oni su aktivni sastojci skupine droga pod nazivom „Spice“. Budući da se kratko vrijeme nalaze u upotrebi, još uvijek nema dovoljno literaturnih podataka o toksičnosti, farmakološkom djelovanju i metabolizmu. Niti sintetski katinoni još uvijek nisu dovoljno istraženi. To su derivati katinona, psihoaktivnih spojeva koji su strukturalno najbliži amfetaminu. Dostupni su u obliku bijelog ili svijetlo žutog praha. Cilj ovog istraživanja bio je ispitati koliko su ljudi informirani o novim psihoaktivnim tvarima, pogotovo sintetskim kanabinoidima i sintetskim katinonima, te da li ih konzumiraju U istraživanju je sudjelovao 61 ispitanik – 33 osobe muškog i 28 osoba ženskog spola u dobi od 15 do 35 godina. Za potrebe istraživanja sastavljena je anonimna anketa od 18 pitanja i zatim podijeljena na društvenim mrežama. Rezultati su pokazali da mladi ljudi u dobi od 15 do 21 godine, odnosno adolescenti, čine najveći broj onih koji konzumiraju nove psihoaktivne tvari, odnosno sintetske kanabinoide i sintetske katinone. Također, većina ispitanika je slabo informirana o novim drogama, što znači da bi u medijima, školama, internetu i literaturi više pažnje trebalo posvetiti toj temi. On the European market more and more new psychoactive substances that mimic the effects of controlled drugs can be found. The synthetic cannabinoids and synthetic cathinones together make nearly two-thirds of new drugs. They are sold as a legal substitutes for marijuana and stimulants. Although they contain a label that they are not for human consumption, the rate of abuse in the world is growing rapidly, especially among adolescents. Synthetic cannabinoids appear as herbal blends, powders or resins. They are the active ingredients of drugs called "Spice". Whereas they are in use for a short time, there is still no sufficient literature data on toxicity, pharmacological action and metabolism. Neither synthetic cathinones still have not been adequately investigated. These are derivatives of cathinones, psychoactive compounds that are structurally closest to amphetamine. They are available as a white or pale yellow powder. The aim of this study was to investigate how much people are informed about new psychoactive substances, especially synthetic cannabinoids and synthetic cathinones cathinones, and are they consumed. The study included 61 participants - 33 males and 28 females aged 15-35 years. An anonymous survey of 18 questions was made for the study and then shared into social networks. The results showed that young people aged 15-21, ie adolescents, make the largest number of those who use new psychoactive substances, respectively synthetic cannabinoids and synthetic cathinones. Also, most of the participants have little awareness about new drugs, which means that in the media, schools, internet and literature more attention should be paid to this issue.

Pušenje je - jedan od najvećih javnozdavstvenih problema današnjice. Glavni krivac za štetni uĉinak pušenja ĉini kancerogeni nikotin koji je sadrţan u duhanskom dimu. Osim vrlo dobro istraţenog nikotina, danas su poznate i brojne druge ĉestice koje su sadrţane u duhanskom dimu i imaju vrlo nepovoljan pa i kancerogeni uĉinak na ljudsko zdravlje. Iz tog razloga, razumljivo je da se osim pronalaska rješenja kojim bi se pojedincu olakšao proces prestanka pušenja, vrlo ĉesto traţila i zdravija alternativa pušenju. E-cigareta, kao „zdravija― varijanta duhanskih cigareta, vrlo brzo je postala popularna meĊu ovisnicima o duhanskoj cigareti. Budući da se nikotin, koji ima kljuĉnu ulogu u stvaranju ovisnosti, takoĊer nalazi i u e-cigaretama, ne ĉudi da je doista mnogo pušaĉa zamjenilo konvencionalnu cigaretu s onom elektriĉnom. Iako su već mnoga objavljena, a i dalje se vode mnoga druga istraţivanja, o pravoj štetnosti te dugoroĉnim posljedicama, korištenja e-cigareta, danas još uvijek nedovoljno znamo. Isto tako s obzirom da se radi o novoj kategoriji prizvoda i kako e-cigarete do sada nisu bile zakonski regulirane, uoĉeni su mnogi propusti u oznaĉavanju i kategorizaciji samog proizvoda. UvoĊenjem nove direktive o duhanskim proizvodima koja se odnosi i na e-cigarete, ţeli se zakonom regulirati ta skupina proizvoda te na taj naĉin zaštititi potrošaĉa. Naime, tzv. „parenje― e-cigarete mogla bi postati nova stara ovisnost 21. stoljeća. I jedan vrlo ozbiljni javno zdravstveni problem, ĉemu u prilog govori i ĉinjenica da se u relativno kratkom vremenu proširila meĊu relativno velikim brojem pušaĉa. Smoking is one of the biggest public health problems of our time. The main culprit for the harmful effect of smoking is carcinogenic nicotine contained in tobacco smoke. In addition to the well-researched nicotine, today many other particles are known that are contained in the tobacco smoke, and have a very unfavorable, even carcinogenic effects on human health. For that reason, it is understandable that, in addition to finding a solution that would facilitate the process of quitting smoking, often are sought healthier alternatives to smoking. E-cigarettes, as "healthier" version of tobacco cigarettes, quickly became popular among users of the tobacco cigarettes. Because the nicotine, which has a key role in the creation of dependency, is also contained in the e-cigarettes, it is not surprising that many smokers actually replace the conventional cigarette with the electric one. Although many studies have already been published, the right identification and long-term consequences of the use of e-cigarettes, are still not known. Also, considering that it is a new category of product and how e-cigarettes have not been regulated by law, there are many gaps in labeling and categorization of the product itself. With the introduction of the new directive on tobacco products that applies to e-cigarettes, the law wants to regulate the product groups and thus protect the consumers. The "vaping" of e-cigarettes could be the next old dependence of the 21st century and a very serious public health problem, which is supported by the fact that, in a relatively short period of time, it spred among a relatively large number of smokers.

Oksidativni stres definira se kao poremećaj u ravnoteţi oksidacijsko- redukcijskih procesa u organizmu u kojem prooksidansi nadvladaju antioksidacijski potencijal. To moţe rezultirati nizom patofizioloških poremećaja praćenih upalom ili oštećenjem tkiva. Mikroglija stanice, kao rezidualni makrofazi mozga, imaju ulogu nadziranja zdravlja ţivčanog tkiva. U uvjetima hipoksije, kao što je moţdani udar, dolazi do njihove aktivacije, pri čemu one eksprimiraju razne parametre, pa tako i enzim iNOS koji je jedan od indikatora oksidacijskog stresa. Celastrol, ekstrakt biljke Tripterygium wilfordii, spada u skupinu pentacikličkih triterpena. Zbog svojih antioksidacijskih i protuupalnih svojstava učinkovito se upotrebljavao u tradicionalnoj medicini za liječenje autoimunih bolesti, astme, kroničnih upala i neurodegenerativnih bolesti. Cilj ovog istraţivanja bio je ustanoviti da li celastrol, kao potencijalno antioksidacijsko sredstvo, moţe spriječiti aktivaciju mikroglija stanica te na taj način prevenirati razvoj oksidacijskog stresa u uvjetima hipoksije. Dobiveni rezultati navode na zaključak da celastrol dovodi do smanjenja ekspresije iNOS-a, a posljedično tome i oksidacijskog stresa stanice., Oxidative stress is defined as a non balanced redox condition where prooxidants overpower the antioxidant potential what can result in series of pathophysiological disorders followed by an infection or tissue damage. Microglial cells, as residual macrophages of the brain, have the function to monitor neural tissue health. They are activated in a case of hypoxia, like a stroke, when they express different parameters, including iNOS enzyme which is an indicator of oxidative stress. Celastrol, an extract of the plant Tripterygium wilfordii, is a member of pentacyclic triterpenes. It has been efficiently used in the traditional medicine to treat autoimmune diseases, asthma, chronic infections and neurodegenerative deseases owing to its antioxidative and anti-inflammatory characteristic. The purpose of this research was to perceive if celastrol, as a potential antioxidative agent, can prevent microglial cells activation and this way also prevent the oxidative stress growth in the case of hypoxia. The results indicate the number of microglial cells treated with celastrol have, in regard to controle group, reduced and there is an after effect - a reduced induction of the iNOS enzymes. We can conclude that celastrol has revealed it self as a successful inhibitor of microglial cells activaton, which also contributed oxidative stress reduction, and it can also beused as a potential antioxidative resort invarious deseases treatments.

Kanabis je jedna od najstarijih kultiviranih biljnih vrsta u svijetu. Tijekom povijesti značajno je utjecao na razvoj poljoprivrede, medicine, društva, umjetnosti, proizvodnje tekstila i pomorstva. Korišten je kao lijek u cijelom svijetu više od 5000 godina, primarno zbog svojih analgetskih, sedativnih, hipnotičkih i apetit stimulirajućih svojstava. Korištenje te daljnje istraţivanje kanabisa zaustavljeno je nakon njegove zabrane 30-ih godina 20. stoljeća u SAD-u. Usprkos protivljenju tadašnjih liječnika, zakon je stupio na snagu te je kanabis uklonjen iz farmakopeje. Otkrićem Δ9-tetrahidrokanabinola (THC), aktivnog sastojka kanabisa, 1964. godine ponovno je potaknut interes za njegovim istraţivanjem. Otkrićem endokanabinoidnog sustava početkom 90-ih godina 20. stoljeća ostvaren je veliki napredak u razumijevanju farmakologije kanabisa. To je sustav u mozgu koji se sastoji od prirodno prisutnih neuromodulatornih lipida, endokanabinoida, te njihovih receptora. Ovaj sustav je uključen u razne fiziološke procese kao što su memorija, apetit, nocicepcija i raspoloţenje te je odgovoran za psihoaktivna svojstva THC-a. Lijekovi na bazi kanabisa se trenutno koriste za tretman refraktorne mučnine i povraćanja u pacijenata na kemoterapiji, povećanje apetita kod anoreksije i kaheksije u oboljelih od AIDS-a, kod kronične neuropatske boli te olakšanje boli i spazama mišića u oboljelih od multiple skleroze. Ostali potencijalni terapijski učinci koji se trenutno istraţuju su: tumori, autoimune bolesti, neurološke i neurodegenerativne bolesti. Iako ne izaziva ovisnost osim u stalnih korisnika, trenutno je kanabis još uvijek klasificiran kao teška droga i ilegalan je u većini zemalja svijeta, ali pod utjecajem rastućeg broja znanstvenih publikacija o medicinskom kanabisu posljednjih godina, sve više drţava odlučuje se za njegovu legalizaciju., Cannabis is one of the oldest cultivated crops in the world. Throughout mankind's history cannabis has influenced the development of agriculture, medicine, society, religion, art, clothing, seamanship and other fields. Cannabis has been used as a medicine all around the globe for more than 5000 years mainly for it’s analgesic, sedative, hypnotic and appetite stimulating properties. The usage and research of cannabis has been stopped due to its prohibition in the 30's in the USA. Despite the disapproval of physicians, the law was passed and cannabis was consequently removed from textbooks. Δ9-tetrahydrocannabinol, the active ingredient of the cannabis plant was isolated in 1964. The discovery of the endocannabinoid system in the early 90's, has been a great breakthrough in understanding the pharmacology of cannabis. It is a system comprising of naturally occurring neuromodulatory lipids, endocannabinoids and their matching receptors in the brain. It is involved in a wide variety of physiological processes, such as mood, pain-sensation, memory and appetite and also mediates the psychoactive effects of THC. Cannabis-based medicines are currently being used for treating refractory nausea and vomiting in patients undergoing chemotherapy, loss of appetite in cachexia and anorexia in both cancer and AIDS patients, chronic pain and muscle spasms following multiple sclerosis. Potential therapeutic effects are being researched for other conditions such as cancer, autoimmune diseases, neurological and neurodegenerative disorders. Although cannabis is not addictive, except in heavy users, it is still regarded as a heavy drug and is illegal in most parts of the world. But under the influence of vast numbers of scientific publications on medical cannabis, the number of countries willing to legalise this plant is growing.

Cilj: Pokazati mijenjaju li se hemodinamski parametri i pokazatelji arterijske elastičnosti u zdravih perimenopauzalnih žena tijekom vremenskog perioda od godine dana. Ispitanici i metode: Istraživanje je provedeno na kohorti od 8 zdravih ispitanica koje su na temelju pregleda i laboratorijskog nalaza koncentracije estradiola i FSH–a ušle u razdoblje perimenopauze. Isključni kriteriji su bili: dijabetes, arterijska hipertenzija, hiperlipidemija, autoimune bolesti, ovariektomija, hipergonadizam, anamneza koronarne bolesti, pušenje, pretilost, uzimanje hormonske nadomjesne terapije i oralne kontracepcije. U siječnju i veljači 2015. godine provedeno je prvo mjerenje, a nakon godinu dana drugo mjerenje istih ispitanica. Hemodinamski parametri i pokazatelji arterijske elastičnosti bili su mjere ishoda: periferni sistolički i dijastolički arterijski tlak te tlak pulsa, središnji sistolički arterijski tlak i središnji tlak pulsa, središnji augmentacijski indeks i brzina širenja pulsnog vala. Mjerenja su učinjena primjenom uređaja Arteriograph (TensioMed TM Kft, Budimpešta, Mađarska), čiji se princip rada temelji na oscilometriji. Rezultati: Najmlađa ispitanica imala je 47 godina, a najstarija 54 godine. Indeks tjelesne mase ispitanica bio je u rasponu od 20,9 kg/m2 do 24,8 kg/m2. Tijekom vremenskog perioda od godine dana između mjerenja nije bilo promjena u mjerenim antropometrijskim obilježjima ispitanica. Tijekom vremenskog perioda od godinu dana nije došlo do značajnog porasta ni sistoličkog (P=0,844), niti dijastoličkoga tlaka (P=0,609). Medijan vrijednosti početnih mjerenja (1. mjerenje) bio je 111 mmHg za sistolički tlak i 73 mmHg za dijastolički tlak. Medijan vrijednosti nakon godine dana (2. mjerenje) bio je 112 mm Hg za sistolički, a 76 mm Hg za dijastolički tlak. Nije se mijenjao niti tlak pulsa (P=0,328). Medijan tlaka pulsa u prvom mjerenju bio je 41 mmHg, a u drugom mjerenju 38 mmHg. Vrijednosti središnjeg sistoličkog tlaka pokazale su veću varijabilnost, ali se također nisu mijenjale tijekom godine. Medijan je u oba mjerenja bio 110 mmHg. Središnji tlak pulsa se neznačajno smanjio (P=0,148), od 32 mmHg u 1. mjerenju na 29 mmHg u 2. mjerenju. Središnji augmentacijski indeks (AIx) i brzina prenošenja pulsnoga vala nisu se značajno promijenile tijekom godine dana. Središnji je augmentacijski indeks u prvom mjerenju bio 36,6 %, a u drugom mjerenju 38,1 %, P=0,109. Medijan je vrijednosti brzine prenošenja pulsnog vala u prvom mjerenju bio 9,2 m/s, a u drugom mjerenju 9,6 m/s, P=0,297. Zaključak: Iako su koncentracije estradiola i FSH-a te ginekološki nalaz ukazivali da su ispitanice ušle u razdoblje perimenopauze nije došlo do očekivanog smanjivanja arterijske elastičnosti tijekom godine dana. U istraživanje su uključene zdrave žene, te su svi izmjereni hemodinamski parametri i pokazatelji arterijske elastičnosti bili u rasponima fizioloških vrijednosti. Zaključujemo da u relativno kratkom vremenskom periodu od godine dana nije došlo do izražaja mogućih početnih patofizioloških zbivanja na stjenkama „zdravih” arterija koji bi se očitovali smanjivanjem arterijske elastičnosti., Objectives: To study if the hemodynamic parameters and arterial elasticity indicators of healthy perimenopausal women change during the course of a year. Patients and Methods: The study has been conducted in a cohort of eight healthy patients who have reached menopause based on the physical examination and the results of estradiol and FSH concentration laboratory tests. Exclusion criteria have been a history of diabetes, arterial hypertension, hyperlipidaemia, autoimmune disease, ovariectomy, hypergonadism, coronary disease anamnesis, smoking, obesity, taking hormone replacement therapy and oral contraceptives. The first measurement was taken in January and February 2015 and a year later the same patients´ measurements were taken once more. Hemodynamic parameters and arterial elasticity indictors served as outcome measures: peripheral systolic and diastolic arterial pressure as well as pulse pressure, central systolic arterial pressure and central pulse pressure, central augmentation index and pulse pressure velocity. The measurements were taken by means of Arteriograph (TensioMed TM Kft, Budapest, Hungary), a device employing the oscillometric principle Results: The youngest test subject was forty-seven years old and the oldest one was fifty-five. The patients' body mass index varied from 20.9 kg/ m2 to 24.8 kg/m2.During the course of a year there have been no differences in the measured anthropometric variables. During this period of time there have been no significant rise of the systolic (P=0.844) of diastolic pressure (P=0.609). Initial measurements' median (the first measurements) was 111mmHg for systolic pressure and 73 mmHg for diastolic pressure. A year later, the measurements' median (the second measurements) was 112 mmHg for systolic and 76 mmHg for diastolic pressure. Pulse pressure has neither changed (P=0.328). Initial pulse pressure median was 41 mmHg while the second measurement's median was 38 mmHg. Central systolic pressure's values have displayed greater variability; however there has been no change during the course of a year. Both measurements' median was 110 mmHg. The central pulse pressure has insignificantly decreased (P=0.148) from 32 mmHg in the initial measurement to 29 mmHg in the second measurement. Central augmentation index (AIx) and pulse wave velocity has not changed significantly. Central augmentation index of the initial measurements was 36.6% and in the following measurements it was 38.1%, P=0.109. Pulse wave velocity median of the initial measurement was 9.2 m/s and in the second measurement it was 9.6 m/s, P=0.297. Conclusion: Even though the estradiol and FSH concentration as well as the gynaecological examination have shown that the patients have reached perimenopause, there have been no expected decrease in the arterial elasticity in the course of a year. The study has included healthy women and all the measured hemodynamic parameters and arterial elasticity indicators have been within the physiological values. Thus, it is possible to conclude that during a relatively short period of time – one year, there has been no indications of possible pathophysiological processes on the “healthy“ arterial walls that would be indicated by means of decreased arterial elasticity.

The prescribing of medicines is a fundamental component of care for the elderly ; however, there is increasing concern with polypharmacy and its impact on morbidity, mortality and costs. As a result, long-term prescription- medicine use and the prevalence of polypharmacy in the elderly in the Republic of Srpska were analyzed. The findings were subsequently used to suggest potential future measures. A retrospective study of all elderly patients during 2005-2010 stratified by age group (three groups), sex and long- term medicine use was performed. Polypharmacy (five or more medicines) increased from 1.4% of the elderly taking medicines long-term to 3.6% by 2010, with 53.6% of elderly taking two or more medicines long- term. The most prevalent diseases were cardiovascular diseases and diabetes. Most prescriptions were in accordance with recent guidelines ; however, there was a concern with appreciable prescribing of digoxin and aminophylline. Whilst polypharmacy rates are low in the Republic, the increasing rate is a concern. Further studies are planned.

Popularnost anaboličkih androgenih steroida ( AAS ) u zadnjih trideset godina u velikom je porastu. Iako AAS , uz pravilan trening, može znatno povećati tjelesnu snagu, nuspojave koje se javljaju njegovim dužim korištenjem izrazito su opasne za zdravlje korisnika, u ovisnosti o njegovoj genetskoj predispoziciji i broju receptora na stanicama. Među najčešće nuspojave korištenja AAS spadaju pojava ginekomastije, akne, ćelavost, inhibicija lučenja vlastitog testosterona, oštećenja jetre i bubrega, oštećenje krožilnog sustava, neurotoksičnost i promjena imunološkog sistema. Predmet razmatranja rada bila je prvenstveno informiranost studenata o AAS. Ispitivanje infomiranosti provedeno je pisanim anketnim listovima podijeljenim među 100 studenana Medicinskog i 100 studenata Pomorskog fakukteta u Rijeci. Cilj rada bio je međusobno usporediti informiranost studenata navedenih fakulteta o nuspojavama AAS i iznijeti kratki prikaz mišljenja studenata da li AAS predstavljaju veliki javno-zdravstveni problem i da li bi sportaši trebali imati slobodan pristup ograničenoj količini AAS-a. Iz dobivenih rezultat ankete primjećuje se da su studenti Medicinskog fakulteta bolje upoznati sa nuspojavama uzimanja AAS-a. Većina studenata djelomično je informirana o učincima AAS-a , najčešće putem internetskih izvora. Iako AAS ne predstavljaju veliki javnozdravstveni problem, bolje informiranje populacije o njima nužno je za sprečavanje njihove zlouporabe. Popularity of anabolic androgenic steroids ( AAS ) in last thirty years has been in steady rise. Although AAS, with proper training, can dramatically increase physical strength, side effects that can occur after using them for longer time can be extremely dangerous for overall health of their users, depending primarily on their genetical predispositions and number of AR receptors on cells. The most common side effects of longer AAS usage are: gynecomastia, acne, baldness, inhibition of normal testosterone levels, damage to liver and kidneys, damage to cardiovascular system, neurotoxicity and changes to immune system. The subject of study was to see how much are students informed about AAS. This study was conducted by written survey papers that were divided between 100 students of Medical college and 100 students of Maritime college in town of Rijeka. The goal of this paper was to compare knowledge of AAS side effects between students and give a brief overview of students thoughts if AAS are major public health problem. From survey results it can be seen that Medical college students are more familiar with AAS side effects. Most students are partially informed about AAS in general, mostly through online sources. Although AAS don't pose major public health issue, better informing of population about them would o a long way into preventing their misuse.

Zdravlje je danas kao i u prošlim vremenima najvažniji preduvijet za sve ostale životne uspjehe, a upravo je naše doba vrijeme otkrivanja nepoznanica vezanih za ljudsko zdravlje. Homeopatija, kao alternativna medicina, u današnje vrijeme postaje predmet zanimanja javnosti, ali i znanstvenih medicinskih krugova. Iako je homeopatija na našim prostorima još uvijek nedovoljno poznata u svijetu broji veliki broj pobornika koji se odlučuju na primjenu ove terapije. Zakoni homeopatije, individualni pristup i remedije, temelj su osnovne ideje da se „isto istim liječi“ . Temeljem dostupne literature evidentno je da su raspoloživi podaci kontroverzni, od onih koji u cijelosti odbacuju učinkovitost homeopatije do podataka koji su vrlo obečavajući. S obzirom na navedeno, te dugogodišnje iskustvo primjene ove terapije, koja je u nizu zapadnih zemalja prihvaćena kao alternativna dopuna konvencionalne medicine, jasno je da su potrebna daljnja i dodatna istraživanja eventualne učinkovitosti homeopatskih lijekova. Health today, as in times past, is the most important precondition for all other life achievements, and this is our time for discovering unknowns related to human health. Homeopathy as an alternative medicine, today became the object of public interest, but also of scientific medicine. Although homeopathy is still not known in our country, in the world has a large number of supporters who are adopting this therapy. The laws of homeopathy, an individual approach and remedies, are the foundation of the basic idea that "the same is treated the same." On the basis of the available literature, it reveals that the data are controversial than those who completely reject the effectiveness of homeopathy to the data which are very promising. Given this, and the long experience of the application of this therapy, which is in many western countries accepted as an alternative complement to conventional medicine, it is clear that further and additional research about potential effectiveness of homeopathic remedies is required.

Mikroglija stanice predstavljaju obranu SŽS koje ispunjavaju važne zadatke. Tijekom upale dolazi do aktivacije i migracije mikroglija stanica, te oslobađanja medijatora upale. Celastrol, kineska ljekovita biljka se stoljećima uspješno koristi u liječenju raznih bolesti jer ima snažnu terapeutsku učinkovitost za autoimune i upalne bolesti. Cilj ovog rada bio je ispitati djelovanje celastrola na BV-2 mikroglija stanice kojima je inducirana hipoksija u trajanju od 6 h. Praćene su promijene morfoloških obilježja stanica te njihovog broja, i izražaj markera upale COX-2. Smanjenjem broja mikroglija stanica i promjena njihove morfologije pokazatelji su toksičnog učinka celastrola i hipoksije u kombinaciji. Smanjena ekspresija indikatora upale COX-2 dovodi do zaključka da celastrol djeluje protuupalno. Microglial cells are defense of the central nervous system and they have many important tasks. Microglia cells are being activated and they migrate during the inflammation process which also releases inflammatory mediators. Celastrol, chinese medical herb has been used successfully for centuries in the treatment of various diseases because it has a strong therapeutic effect on autoimmune and inflammatory diseases. The aim of this study was to investigate the effect of celastrol on BV-2 microglial cells which were exposed to hypoxia in a period of 6 hours. We looked for morphological changes of microglial cells, their number, and the expression of the marker COX-2. By decrease of the number of microglial cells and by the change in their morphology we see toxic effects of celastrol and hypoxia. Reduced expression of COX-2 indicator of inflammation leads to the conclusion that celastrol has anti-inflammatory activity.

Purpose The purpose of this study was to determine the prevalence of inappropriate prescribing to the elderly and to identify possible gender-related differences in prescribing certain potentially inappropriate medications (PIMs) to outpatients by using large administrative prescription database. Methods Medications prescribed for elderly outpatients (≥ 65 years) in Primorsko-Goranska County, Croatia, who received five or more different drugs simultaneously in 2010, were analyzed. The prevalence of potentially inappropriate drugs prescribed to the elderly was assessed using the new comprehensive protocol developed by authors Mimica Matanović and Vlahović-Palčevski. Results A total of 62.4 % of patients received at least one medication with unfavorable benefit/risk ratio in the elderly. Female patients were given inappropriate medications in a significantly higher percentage than men (69.3 % vs. 50.5 %; p65 years and receiving five or more drugs was potentially inappropriate. Elderly women were prescribed PIMs more often than men. Drugs of concern in female patients were benzodiazepines, antidepressants, and nonsteroidal anti-inflammatory drugs (NSAIDs). In male patients, there was a significantly higher proportion of possible interactions with warfarin, theophylline, and medications affecting the cardiovascular system, such as ACE inhibitors and amiodarone.

Around 90% of antibiotics used in human medicine are prescribed in primary care. At least half of these prescriptions are either unnecessary or inappropriate. Multifaceted interventions have proved useful in improving antibiotic prescribing, but they should be adapted to the context (‘One size does not fit all’ and ‘No magic bullet’ concepts). Behavior change theories are helpful for designing interventions that target healthcare professionals. Recent evidence related to various interventions targeting healthcare professionals are described here (Table 1): education, guidelines, clinical decision support systems, delayed prescribing, patient materials, public commitment, POC diagnostic tests, selective susceptibility reporting, quality indicators, audit and feedback, and restrictive prescribing measures. Interventions targeting the healthcare system have been overlooked so far, even though their impact can be large and sustained. Some examples are given here, including dispensing of antibiotics, financial incentives, and public reporting. Most published studies come from Europe or North America. We need studies from a much greater range of settings. Most interventions have focussed on GPs. In the future, all healthcare professionals should be targeted. Most studies have focussed on RTIs ; we need to develop a better understanding of how much improvement is possible for other conditions and how well suited our current interventions are to achieving this. Patient-centered outcomes remain largely underdeveloped and underreported. Innovative strategies, including those targeting the system organization, should be tested.