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The incidence of neurodegenerative diseases, including Parkinson’s disease (PD), is increasing with the aging of the population. PD is characterized by massive depletion of dopamine as a result of the degeneration of dopaminergic neurons, leading to motor symptoms and other neuropsychiatric and cognitive symptoms.1 Dopamine precursor levodopa (L-dopa) still represents the gold therapeutic standard for PD but long-term treatment can lead to serious side effects. Increased efficacy and better safety of PD treatment may be reached by novel formulation using nanotechnological tools and methods. Here, we present the design and efficacy of nanoformulation based on selenium nanoparticles (SeNPs), which exhibit antioxidant properties and neuroprotective effects.2 SeNPs stabilized with polyvinylpyrrolidone (PVP) were developed as a nanodelivery system for L-dopa. PVP-coated SeNPs were characterized by a hydrodynamic diameter of 82.9 ± 0.5 nm and a zeta potential of -28.0 ± 1.9 mV. The efficacy of such a system was tested using a hemiparkinsonian rat model, achieved by injection of 6-hydroxydopamine into the right hemisphere according to the stereotaxic atlas.3 Four weeks after injections, rats were treated orally with conventional L-dopa and L-dopa loaded on SeNPs for 28 days. Different behavioral assays were used to evaluate the efficacy of the treatments. The motor coordination was tested on the Rotarod apparatus, the neurological severity score (NSS) tests were used for estimating balance, motor coordination, and sensorimotor reflexes, while gait analysis was used to assess the changes in motor impairments in rats before and after surgery.4 Obtained results on improved motor dysfunction and coordination clearly showed beneficial effects of L-dopa loaded on SeNPs in comparison to L-dopa treatment.

Kateheza je unutar evangelizacijskog poslanja Crkve najvažniji oblik učenja i poučavanja vjere i u vjeri onih koji su kršteni i odlučili su slijediti Kristov put. Kao središnja zadaća Crkve kateheza ima ulogu ne samo poučavanja i učenja vjere nego i svoje ispunjenje nalazi u uvođenju vjernika u zajednicu Crkve. Primanjem sakramenata, osobito sakramenata inicijacije kao članovi crkvene zajednice vjernici su pozvani na apostolat, službu služenja i poslanja u svijetu. Unutar tog procesa kateheze inicijacije, ministranta se služba odvajkada ucijepila kao zajednica koja je do današnjih dana prezentna gotovo u svakoj župnoj zajednici. Ovaj rad analizira i istražuje ministrantsku službu, katehezu ministranata s fokusom na poslanje ministranta unutar Crkve. Rad se sastoji od tri dijela. U prvom se prikazuje ministrantska služba kroz razne biblijske primjere, te kroz primjere blaženika i svetaca koji su za ovozemaljskog života na svoj način bili ministranti. Nakon predstavljanja ministrantske zajednice i njezine utemeljenosti na primjerima pokrepljenim Biblijom rad se fokusira na samu bit, to jest na katehezu ministranata. Ona je podijeljena na tri važna djela koja su neophodna za katehezu ministranata a to su: liturgijski aspekt, socijalno-karitativni aspekt i „communio“ to jest zajedništvo. U posljednjem dijelu se predstavljaju njihove karakteristike i oznake, a naglasak se stavlja na zajedništvo kao glavnu karakteristiku ministrantske zajednice. Rad završava trećim poglavljem koje govori o rađanju budućih duhovnih zvanja kroz ministranske zajednice. Posebno su naglašena tri elementa koja su važna za zvanja, a to su: obitelj, župna zajednica i župnik. The Catholic Church has always paid great attention to catechesis. Throughout its long history, the Catholic Church has brought up countless generations of Catholics with the help of Catechesis. Recently, it has been noticed that difficulty in approaching young people. Institutions like the Family and the Catholic Church simply don't reach the young like they used to. The goal of the Catholic Church is to approach children and young people with the help of catechesis in the hope of regaining their trust. Catechesis must be adapted to the group with which the good news is shared to. One of the groups that belong to compulsory catechesis is the altar servants who are the subject of this thesis. The key feature of every ministerial community is catechesis. The initial part of the thesis presents and explains the meaning of ministerial service itself through various biblical examples and by various blesseds and saints who were altar servants in their way during their earthly life. After the presentation of the ministerial community and its foundation on examples supported by the Bible and the lives of various saints and blesseds, we move on to the very essence, that is, the catechesis of altar servers. It is divided into three important parts that are necessary for the catechesis of altar servers, namely: the liturgical aspect, the social-charitable aspect, and "communio", that is, togetherness. In the last part, their characteristics and markings are presented, and the emphasis is placed on togetherness as the main characteristic of the ministerial community. The work ends with the third chapter, which talks about the birth of future spiritual vocations through ministerial communities. Three aspects that are important for spiritual vocations are particularly emphasized, namely: Family, parish community, and Pastor.

Parkinson`s disease is the second most common neurodegenerative disorder (1). It is characterized by early prominent death of dopaminergic neurons in substantia nigra which results in classical motor symptoms of the disease: rigidity, rest tremor, bradykinesia, and postural instability (2). Although initially described more than 200 years ago (3), not a single drug is able to alter the natural history of the disease. Mainstay therapy is levodopa - a precursor in the synthesis of the dopamine - that can cross the blood brain barrier. Since introduction to the therapy, 50 years ago, many improvements have been made to enhance its efficiency and reduce side effects. However, passage of the blood brain barrier is still relatively poor, side effects can pose significant burden and long- term therapy is associated with motor complications. Motor complications are, at least in part, due to the fluctuations of levodopa concentrations in the plasma. In many cases these complications can be so intense that the only options is to discontinue the drug which inevitably leads to rapid decline in the quality of the life. Therefore, new formulations of levodopa, that can increase delivery of the drug to the brain and reduce plasma fluctuations are needed. This study tested the safety of phosphoglucomutase (PGM) functionalized gold nanoparticles (AuNP) as levodopa carrier using differentiated neuroblastoma (SH-SY5Y) cells as in vitro model of Parkinson`s disease. AuNPs shape, size, and surface charge were determined with transmission electron microscopy (TEM), dynamic light scattering (DLS), and zeta potential measurements, respectively. Cell viability and apoptosis induction test were performed using flow cytometry, while oxidative stress was determined by measuring the concentration of reactive oxygen species, glutathione (GSH) and mitochondrial membrane potential. In all experiments levodopa loaded AuNPs were compared with AuNPs and levodopa alone.

The current “gold standard” therapy is levodopa (L-DOPA) due to its effectiveness and ability to permeate the blood-brain barrier (BBB). However, long-term treatment with L-DOPA can lead to serious side effects and increase oxidative stress, thereby worsening the disease [2]. The oxidative stress caused by either L-dopa or dopamine could be lessened by the combination of antioxidants – one that promises is selenium (Se) – an essential trace element that can protect from oxidative damage through selenoproteins [3]. Direct use of Se as an antioxidant supplement is toxic due to a narrow therapeutic index, so Se should be applied in other therapeutical forms. The use of Se in the form of nanoparticles (SeNPs) may elicit the same beneficial effects with reduced toxicity [4]. This study tested the safety of SeNPs as L-DOPA carrier using differentiated neuroblastoma (SH- SY5Y) cells as in vitro model of Parkinson`s disease [5]. SeNPs were prepared via reduction of sodium selenite by L-ascorbic acid and functionalization by polysorbate 20 (SeTWEEN) and poly(vinylpyrrolidone) (SePVP). The shape, size, and surface charge of SeNPs were determined with transmission electron microscopy (TEM), dynamic light scattering (DLS), and zeta potential measurements, respectively. Cell viability and apoptosis induction test were performed using flow cytometry, while oxidative stress was determined by measuring the concentration od reactive oxygen species, glutathione (GSH) and mitochondrial membrane potential. In all experiments L-DOPA loaded SeNPs were compared with SeNPs and L-DOPA alone. L- DOPA loaded SeNPs (1ppm) were non-toxic to differentiated SH-SY5Y cells after 24-hour treatment, while L-DOPA reduced cell viability at the 100 μM, but not at 50 μM concentration. L-DOPA induced oxidative stress at the concentration of 100 µM which was effectively reduced after combining with SeNPs (1 ppm). Results suggest that SeNPs could be a promising approach for the reduction of toxicity caused by L-DOPA.

The development of new strategies to treat Parkinson’s disease suffers from many deficiencies. Common therapy that includes external administration of L-dopa to Parkinson’s disease patients is limited due to the lack of targeting ability.[1, 2] As an alternative for conventional therapeutic drugs, selenium nanoparticles (SeNPs) constitute an attractive carrier platform for targeted drug delivery into the brain.[3, 4] In this study, two different SeNPs were designed using polyvinylpyrrolidone (PVP) and polysorbate 20 (Tween) as surface modifiers. Their binding ability for dopamine and L-dopa was evaluated by steady-state fluorescence spectroscopy. The strongest interaction was observed between L-dopa and PVP-SeNPs. Thermodynamic analysis revealed that binding between Tween-SeNPs and L-dopa or dopamine predominantly occurs through van der Waals interactions and hydrogen bonds, while electrostatic interactions govern the binding of L-dopa or dopamine to the PVP-SeNPs. In all cases, interactions were exothermic and spontaneous.

In hospital setting, antimicrobials are one of the most commonly prescribed drugs. Due to antimicrobial resistance and treatment cost, rational antimicrobial therapy has become a global health priority. One of the measures to control bacterial resistance is a hospital list of antimicrobials with restricted use. Rational antimicrobial therapy includes therapeutic guidelines but often neglects the risk of potential drug-drug interactions (DDI). Patients undergoing complicated surgical procedures are at an increased risk of DDIs. The aim of this study was to analyse the incidence and type of potential clinically significant DDIs of restricted antimicrobial agents in cardiosurgical patients. This prospective study analysed 146 consecutive restricted antimicrobial requests sent to our Central hospital pharmacy for 95 patients. In total, 232 potential clinically significant DDIs were identified and mean number of clinically significant restricted antimicrobial DDIs was 1.6 per request. Potential interactions were identified by Lexicomp® Lexi- InteractTM Online (Lexi-Comp, Inc., Hudson, USA) software which categorizes potential DDIs according to clinical significance in five types (A, B, C, D and X). Categories C, D and X are of clinical concern and require interventions (specific therapy monitoring, therapy modification or avoiding combination). Most common were DDIs with ciprofloxacin while interactions of highest level of clinical significance were found with moxifloxacin and linezolid. The most common Anatomical Therapeutic Chemical (ATC) drug groups involved in DDIs with antimicrobials were antithrombotics, antiarrythmics, antidiabetics and potassium. Necessary interventions regarding potential DDIs involving antimicrobial drugs need to be coordinated with the pharmacotherapy treatment priorities.

Spinal muscular atrophy (SMA) is autosomal recessive disorder characterized by degeneration of spinal cord motor neurons, atrophy of skeletal muscles and generalised weakness. With incidence estimated between 1/6000 and 1/11000, it is the leading genetic cause of infant mortality. Disease is caused by deleterious mutations of SMNl gene, and subsequently decreased levels of SMN protein. Based on the age at onset of symptoms and achieved motor milestone, patients are classified into one of five phenotypic classes (SMA O, SMA I, SMA II, SMA III, SMA IV). Cornerstone of modem diagnosis is genetic screening for homozygous deletion or mutation of the SMNl gene. Until recently, SMA therapy was mainly supportive and despite huge advances in medical technology and patient care, natural history of the disease was barely affected. Twenty years after the discovery of the SMNl gene and its role in SMA, a major step forward was made by approving the first drug for SMA, antisense oligonucleotide, nusinersen. However, despite great enthusiasm within SMA community, following approval, nusinersen has at the same time created many ethical, medical and financial challenges. Many of which are also reflected upon the recently approved gene therapy for SMA.

Spinalna mišićna atrofija (SMA) je autosomno recesivni poremećaj karakteriziran degeneracijom motornih neurona kralježničke moždine, atrofijom skeletnih mišića i generaliziranom slabošću. Javlja se s učestalosti od otprilike 1/6000 do 1/11000 živih poroda. Bolest je uzrokovana štetnim mutacijama gena za preživljenje motoričkog neurona 1 (engl. survival of motor neuron 1 gene, SMN1) i posljedično sniženim razinama SMN proteina. Iako patogeneza nije razjašnjena, vrlo je vjerojatno kako smanjene razine SMN proteina dovode do poremećaja u prekrajanju brojnih gena. Pacijenti se klasificiraju u jedan od pet fenotipskih razreda (SMA 0, SMA I, SMA II, SMA III, SMA IV) na temelju dobi nastupa simptoma i postignutih ključnih točaka motoričkog razvoja. Unatoč klasifikaciji u diskretne razrede, SMA fenotipovi tvore kontinuirani spektar od najtežeg (SMA tip 0) do najlblažeg oblika (SMA tip IV), sa značajnim varijacijama unutar pojedinih razreda. Elektromiografija i biopsija mišića su nekada bili osnova za dijagnostiku SMA, međutim, genetsko testiranje na homozigotnu deleciju ili mutaciju SMN1 gena pokazalo se učinkovitijim i specifičnijim. SMA terapija je donedavno bila uglavnom suportivna i nije utjecala na tijek bolesti, unatoč značajnim naprecima u kvaliteti njege i skrbi za oboljele. Dvadeset godina nakon otkrića SMN1 gena i njegove uloge u SMA, veliki korak naprijed učinjen je je odobravanjem prvog lijeka za SMA od strane FDA i EMA, antisense oligonukleotida, nusinersena. Međutim, nusinersen je u isto vrijeme stvorio mnoge etičke, medicinske i financijske izazove koji se također odražavaju na nedavno odobrenu prvu gensku terapiju za SMA. U ovom radu dan je opsežan Spinal muscular atrophy (SMA) is autosomal recessive disorder characterized by degeneration of spinal cord motor neurons, atrophy of skeletal muscle and generalised weakness. Its incidence is approximately 1/6000 to 1/11000 live births. Disease is caused by deleterious mutations of survival of motor neuron 1 gene, SMN1 and subsequently decreased levels of SMN protein. Although pathogenesis isn`t clarified, it is very likely that reduced levels of SMN protein lead to disorders in splicing of numerous genes. Patients are classified into one of the five phenotypic classes (SMA 0, SMA I, SMA II, SMA III, SMA IV) based on the age at onset of symptoms onset and achieved motor milestones. Despite the classification in discrete classes, SMA phenotypes form a continuous spectrum from the most severe (SMA type 0) to the most mild form (SMA type IV), with significant variations within individual classes. Electromyography and muscle biopsy were once the basis for SMA diagnostics, however, genetic testing for homozygous deletion or mutation of the SMN1 gene has proven itself more effective and more specific. SMA therapy was, until recently, mainly supportive, and despite huge advances in medical technology and patient care, it didn`t have the power to influence natural history significantly. Twenty years after the discovery of the SMN1 gene and its role in SMA, a major step forward was made by approving the first drug for SMA by FDA and EMA, antisense oligonucleotide, nusinersen. However, despite the great enthusiasm within the SMA community, following approval, nusinersen has at the same time created many ethical, medical and financial challenges that are also reflected in the

Cilj ovog istraživanja bio je ispitati uzrokuju li nanočestice srebra (AgNP) promijene u parametrima oksidacijskog stresa u klijancima duhana (Nicotiana tabacum L.) te može li se toksični učinak AgNP spriječiti dodatkom cisteina, kelatora srebra. Klijanci duhana bili su tjedan dana izloženi AgNP stabiliziranim polivinilpirolidonskim omotačem (AgNP-PVP) u koncentracijama 25, 50 i 100 μM. Dio biljaka bio je izložen AgNP u kombinaciji s cisteinom (koncentracije cisteina: 125, 250 i 500 μM) te samom cisteinu (125, 250 i 500 μM). Nakon tretmana u ekstraktu biljnog tkiva spektrofotometrijski je određena koncentracija proteina te koncentracije parametara oksidacijskog stresa proteinskih karbonila (PC) i malondialdehida (MDA). Dobiveni rezultati statistički su obrađeni (ANOVA i post hoc Duncan test, razina značajnosti p < 0, 05). Tretman s AgNP, AgNP + cistein i sam cistein uzrokovali su značajan porast koncentracije proteina u odnosu na kontrolu. Isti također nisu imali utjecaj na koncentraciju PC. Koncentracija MDA opadala je porastom koncentracije AgNP, a nakon tretmana s AgNP + cistein zabilježeno je značajnije povišenje koncentracije MDA (dok su tretman s AgNP + cistein i cistein uzrokovali porast MDA). Možemo zaključiti da tretman s AgNP u ovim uvjetima očito nije izazvao značajan oksidacijski stres u duhanu.

Moamer el Gadafi nakon dolaska na vlast u Libiji 1969. započeo je s vrlo ambicioznom i kontroverznom vanjskom politikom koja mu je donijela niz kratkotrajnih uspjeha, ali još više dugoročnih neuspjeha te u konačnici i svrgavanje s vlasti i smrt. U radu je prikazano Gadafijevo odrastanje te političko i ideološko sazrijevanje, kao i osnovne karakteristike njegove vladavine i ideološkog sklopa koji su u značajnoj mjeri odredili njegovu vanjsku politiku. Također se razmatraju odnosi Gadafijeve Libije s pojedinim državama svijeta te položaj Libije u međunarodnoj zajednici u različitim razdobljima Gadafijeve vladavine.

U radu su opisani polimerni materijali, postupak i sustav za injekcijsko prešanje te glavni parametri koji utječu na svojstva injekcijski prešanog otpreska. U eksperimentalnom dijelu rada istražen je utjecaj temperature kalupne šupljine na skupljanje otpreska dobivenog injekcijskim prešanjem.

Pregled inovativnih tehnologija u autobusnom prijevozu, mogućnost primjene električnih autobusa na linijama javnog gradskog prijevoza, analiza troškova i koristi primjene električnih autobusa na linijama javnog gradskog prijevoza

Koncepcija ovog diplomskog rada utemeljena je na analizama trenutnog stanja segmenta poslovnog zrakoplovstva u Europi i svijetu te potencijalima razvoja u Republici Hrvatskoj temeljenim na infrastrukturnom i gospodarskom potencijalu u kontekstu dugoročnog pristupa regionalnog razvoja prometne mreže poslovnog zrakoplovstva. Cilj diplomskog rada usmjeren je na istraživanje razvoja poslovnog zrakoplovstva u Europi te njegovog utjecaja koje ono ima na ostale segmente zračnog prometa, a posebno na linijski zračni promet. Rad je sadržajno koncipiran u šest poglavlja. U uvodnom poglavlju postavljeni su tema i problematika istraživanja kao i cilj rada i tematika istraživanja na temelju dosadašnjih znanstvenih istraživanja te je predstavljena struktura rada. U drugom poglavlju rada data je definicija i klasifikacija poslovnog zrakoplovstva na temelju različitih tipova poslovnih zrakoplova i operatera koji se pojavljuju u ulozi pružatelja usluge prijevoza putnika i robe poslovnim zrakoplovima. Problematika međunarodnog konteksta razvoja poslovnog zrakoplovstva obrađena je u trećem poglavlju slijedom dosadašnjih istraživanja i analiza. U ovom poglavlju obavljene su detaljne analize dosadašnjeg trendova rasta poslovnog zrakoplovstva kao i prognoze budućeg rasta ovoga segmenta. Status poslovnog zrakoplovstva u Europi naziv je četvrtog poglavlja u kojemu je obavljena analiza integriranosti europskog poslovnog zrakoplovstva u tokovima europskog zračnog prometa te njegov utjecaj na ostale segmente zračnog prometa. U petom poglavlju pod nazivom potencijali razvoja poslovnog zrakoplovstva u Hrvatskoj obavljena je analiza infrastrukturnih, gospodarskih te flotnih potencijala na temelju kojih bi Republika Hrvatska u budućnosti ravnopravno participirala u europskim tokovima poslovnog zrakoplovstva. U posljednjem poglavlju kao zaključak su izvedeni konačni rezultati istraživanja obrađenih u ovom radu.