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Vitamin D
No full textVitamin D grupni je naziv za skupinu vitamina topivih u mastima. Smatra se jednim od najstarijih
prohormona na Zemlji. Najpoznatije vrste vitamina D su vitamin D2 (ergokalciferol) i vitamin D3
(kolekalciferol). Izvori vitamina D2 su biljnog porijekla dok su izvori vitamina D3 životinjskog porijekla.
Aktivni oblik vitamina D je kalcitriol (1,25-dihidroksikolekalciferol). Glavni izvor vitamina D je sunce,
točnije UVB zračenje. Pritom treba naglasiti da sunčanje u svrhe sinteze vitamina D treba prakticirati
bez korištenja zaštitnog faktora, a opet paziti i na to da ne bismo pocrvenili. U optimalnim uvjetima naša
koža može sintetizirati od 10 000- 20 000 IU (od engl. international units, internacionalnih jedinica)
vitamina D u 30 minuta, nakon čega sinteza vitamina D prestaje. Osim što igra vrlo važnu ulogu u
očuvanju zdravlja kostiju i imunosnog sustava, sve više se ističe njegova korist u brojnim bolestima, a
vrlo važnu ulogu ima i tijekom trudnoće i za majku i za fetus te kasnije za novorođenče. Jako puno ljudi
diljem svijeta ima hipovitaminozu vitamina D, koja se dijagnosticira mjerenjem koncentracije 25-
hidroksivitamina D, 25(OH)D u krvi, točnije u serumu. Radi nedostatka vitamina D u organizmu može
doći do raznih komplikacija i oboljenja. S druge strane, prevelike doze vitamina D u organizmu uzrokuju
hipervitaminozu pa radi toga treba paziti da se preporučena doza ne prekorači jer u suprotnom može
uzrokovati neželjene nuspojave i toksičnost. Kako bi se izbjegao neželjeni utjecaj, vitamin D treba
uvijek uzimati pod liječničkim nadzorom.Vitamin D is a group name for a group of vitamins which are soluble in fats. It is considered one of the
oldest prohormones on earth. The most common types of vitamin D are vitamin D2 (ergocalciferol) and
vitamin D3 (cholecalciferol). Sources of vitamin D2 are of plant origin, whereas vitamin D3 sources are
of animal origin. The active form of vitamin D is calcitriol (1,25-dihydroxycholecalciferol,
1,25(OH)2D). The main source of vitamin D is the sun, more precisely its UVB radiation. It needs to be
clear that sunbathing in the means to synthesize vitamin D needs to be done without sunscreen, but
avoiding sunburn. In optimal conditions our skin can synthesize from 10 000 – 20 000 IU (international
units) of vitamin D in 30 minutes, after that the synthesis of vitamin D naturally stops. In addition to
playing a very important role in maintaining bone and immune system health, its benefits in many
diseases are increasingly emphasized and it plays a very important role during pregnancy for both
mother and fetus and also later for the newborn. A lot of people around the world have vitamin D
hypovitaminosis which is diagnosed by measuring the concentration of 25 hydroxyvitamin D, 25(OH)D
in the blood, more precisely in the serum. Due to the lack of vitamin D in the body, various complications
and diseases can occur. On the other hand, overdoses of vitamin D in the body cause hypervitaminosis,
so care should be taken not to exceed the recommended dose because otherwise it can cause unwanted
side effects and toxicity. To avoid side effects, vitamin D should always be taken under medical
supervision
Cistična fibroza: patofiziologija i terapijski pristupi
No full textCistična fibroza multisistemska je autosomno recesivna genetska bolest. Unutar zadnjih nekoliko godina napravljeni su veliki koraci u razumijevanju patofiziologije cistične fibroze, što je omogućilo pretpostavku mehanizma koji uzrokuje kliničku sliku pacijenata. Otkriće CFTR (engl. cystic fibrosis transmembrane conductance regulator) gena 1989. godine, omogućilo je pretpostavku strukture i funkcije CFTR proteina. Nakon toga otkrića opisano je više od 2000 varijanti CFTR gena te njihov utjecaj na količinu i funkciju CFTR proteina. Uloga CFTR proteina kao ionskog kanala za transport klorida i bikarbonata te utjecaj na različite epitelne stanice organa i mukusa, sada su bolje shvaćene. Mehanizmi u pozadini osjetljivosti na infekciju također su pretpostavljeni, a uključuju nepravilnosti u sastavu, volumenu i kiselosti površinske tekućine dišnih putova (engl. airway surface liquid, ASL); promjene u anatomiji i funkciji submukoznih žlijezda te deficijencije u sustavu mukocilijarnog klirensa. Dotaknute su brojne hipoteze koje bi objasnile prekomjerni upalni odgovor, a uključuju oslabljen mukocilijarni klirens, perzistentnu hipoksiju, lipidne abnormalnosti, disproporcije proteaza i antiproteaza te neravnotežu oksidansa i antioksidansa. Osim patofiziologije cistične fibroze, ovaj rad osvrće se i na terapijske pristupe ovoj bolesti. Osim aktualnih terapija, ovaj rad donosi pregled
nekih od terapijskih pristupa, koji su još uvijek u razvoju, odnosno u pretkliničkim i kliničkim fazama ispitivanja. Neki od tih terapijskih pristupa uključuju aktivatore, potencijatore i efektore, gensku terapiju, mRNA terapiju, terapiju antimikrobnim lijekovima (terapije na simptomatskoj razini), terapiju inhibitorima, oligonukleotidima, gensku terapiju, editiranje gena te različite kombinirane terapije.Cystic fibrosis is a multisystem autosomal recessive genetic disease. In the last few years, huge steps have been made in understanding cystic fibrosis pathophysiology, which allowed hypothesis of mechanism causing mainfestation of the disease. Discovery of CFTR gene in 1989. allowed assumption of the structure and function of CFTR protein. Since the
discovery, more than 2000 variants of the CFTR gene have been described, as well as their influence on the amount and function of the CFTR protein. Now, role of the CFTR protein as an ionic channel for chloride and bicarbonate transport, and their influence on different epithelial cells of various organ and mucus, are better understood. Mechanisms behind infection susceptibility have also been hypothesized, and they include abnormalities in composition, volume and acidity of airway surface liquid (ASL); changes in anatomy and function of submucosal glands and the deficiency in mucociliary clearance. A lot of hypothesis have been observed, that would explain excessive inflammatory response, and they include impaired mucociliary clearance, persistent hypoxia, lipid abnormalities, protease/antiprotease disproportion and oxidant/antioxidant imbalance. Except the pathophysiology of cystic fibrosis, this paper also focuses on therapeutic approaches for the disease. In addition to current therapies, this paper brings a review of some therapeutic approaches, still in the development phase or preclinical and clinical trials phase. Some of those approaches include activator, potentiator and effector therapy, mRNA
therapy, antimicrobial therapy (on symptomatic level), inhibitor therapy, oligonucleotides, gene therapy, gene editing and various combined therapies
Pasivna imunoterapija za COVID-19 infekcije
No full textCOVID-19 (prema engl. Coronavirus disease 2019) je respiratorna zarazna bolest koju uzrokuje novi humani koronavirus SARS-CoV-2. Pojavila se u Kini 2019. godine, a ubrzo je 2020. godine prerasla u pandemiju. Glavni simptomi ove bolesti su suhi kašalj, visoka temperatura i glavobolja, ali u teškim slučajevima može dovesti do respiratorne insuficijencije te kardiovaskularnih i neuroloških poremećaja. SARS-CoV-2 potječe od roda Betakoronavirusa te mu se genom sastoji od jednolančane nesegmentirane RNA molekule pozitivne polarnosti. Jedna od glavnih struktura na virusu je površinski protein šiljka (engl. spike) s važnom domenom RBD (prema engl. receptor-binding domain). Ta domena je zaslužna za vezanje virusa za domaćinov ACE2 receptor (prema engl. angiotensin- converting enzyme 2) pa predstavlja važnu metu neutralizacijskih protutijela. Protutijela su glikoproteini koje stvaraju B stanice kad dođu u kontakt s patogenima. U borbi protiv virusa naročito su važna neutralizacijska protutijela koja su specifična za površinske antigene SARS-CoV-2. Jedan od načina kojim se COVID-19 može liječiti je pasivnom humoralnom imunoterapijom. To je vrsta imunoterapije u kojoj se ljudima daju protutijela proizvedena u drugim organizmima ili in vitro. Mogu se koristiti i monoklonska i poliklonska protutijela. Monoklonska protutijela prepoznaju samo jedan određeni epitop patogena dok poliklonska prepoznaju dva ili više. Najvažnije od ovih terapija su one ljudskim protutijelima dobivenim kloniranjem imunoglobulinskih gena iz antigen specifičnih B stanica 1) bolesnika koji su preboljeli COVID-19 ili 2) transgeničnih miševa koji nose gene za ljudske imunoglobuline, nakon njihove imunizacije antigenima SARS-CoV2. Proizvode se i kokteli monoklonskih protutijela kao što su REGEN-COV te poliklonski hiperimuni serum koji nastaje obradom rekonvalescentne plazme. Rekonvalescentna plazma se prikuplja iz osoba koje su preboljele COVID-19, a sadržava neutralizirajuća protutijela protiv SARS-CoV-2. U ovom će se radu detaljnije opisati mehanizmi liječenja infekcija COVID-19 pasivnom imunoterapijom te njen značaj u znanosti.Coronavirus disease 2019 (COVID-19) is an infectious respiratory disease that is caused by a novel human coronavirus SARS-CoV-2. It appeared in China in 2019, and soon turned into a pandemic in 2020. Main symptoms of COVID-19 are dry cough, high fever and sore throat, but in severe cases it can cause respiratory insufficiency as well as cardiovascular and neurological insults. SARS-CoV-2 originates from the Betacoronavirus genera and its genome is made from a single-stranded, nonsegmented positive polarity RNA molecule. One of the main structures on the virus is the spike (S) protein, harbouring an important receptor-binding domain (RBD). RBD serves for virus attachement to the host cells’ angiotensin-converting enzyme 2 (ACE2) receptors and is thus one of the main targets for neutralizing antibodies. Antibodies are glycoproteins made by B cells when they come in contact with pathogens. Neutralizing antibodies for SARS-CoV-2 antigens are especially important when battling SARS-CoV-2. One of the ways COVID-19 can be treated is by passive humoral immunotherapy. It's a type of immunotherapy where people are given antibodies produced in other organisms or in vitro. Both monoclonal and polyclonal antibodies are used for therapy. Monoclonal antibodies recognize one epitope while polyclonal recognize two or more. The most important therapies are those with human antibodies, which are generated upon cloning immunoglobulin genes from antigen specific B cells from 1) patients that recovered from COVID-19 or 2) from transgenic mice that carry genes for human immunoglobulins, after their immunization with SARS-CoV-2 antigens. Monoclonal antibody cocktails like REGEN-COV and polyclonal hyperimmune serum that is made from processed convalescent plasma can also be produced. Convalescent plasma is taken from patients who recovered from COVID-19 and contains neutralizing antibodies against SARS-CoV-2. This paper will provide detais on mechanisms of treating COVID-19 infections with passive immunotherapy, and its significance in science in general
Proteomic analysis of opossum Monodelphis domestica spinal cord reveals the changes of proteins related to neurodegenerative diseases during developmental period when neuroregeneration stops being possible
No full textOne of the major challenges of modern neurobiology concerns the inability of the adult mammalian
central nervous system (CNS) to regenerate and repair itself after injury. It is still unclear why the ability
to regenerate CNS is lost during evolution and development and why it becomes very limited in adult
mammals. A convenient model to study cellular and molecular basis of this loss is neonatal opossum
(Monodelphis domestica). Opossums are marsupials that are born very immature with the unique possibility
to successfully regenerate postnatal spinal cord after injury in the first two weeks of their life,
after which this ability abbruptly stops. Using comparative proteomic approach we identified the proteins
that are differentially distributed in opossum spinal tissue that can and cannot regenerate after
injury, among which stand out the proteins related to neurodegenerative diseases (NDD), such as
Huntington, Parkinson and Alzheimer's disease, previously detected by comparative transcriptomics on
the analog tissue. The different distribution of the selected proteins detected by comparative proteomics
was further confirmed by Western blot (WB), and the changes in the expression of related genes were
analysed by quantitative reverse transcription PCR (qRT-PCR). Furthermore, we explored the cellular
localization of the selected proteins using immunofluorescent microscopy.
To our knowledge, this is the first report on proteins differentially present in developing, non-injured
mammalian spinal cord tissue with different regenerative capacities. The results of this study indicate
that the proteins known to have an important role in the pathophysiology of neurodegeneration in aged
CNS, could also have an important phyisological role during CNS postnatal development and in neuroregeneration
process
Preparation and characterization of the nanocomposite hydrogel based on self-assembly of peptides and poly(vinyl alcohol) for biomedical applications
No full textSupramolekulski samoorganizirajući funkcionalni materijali posjeduju specifična fizikalna i biološka svojstva koja se u nekim slučajevima mogu kontrolirati vanjskim podražajima (temperatura, pH, UV-zračenje). Prepoznati su kao izvrsna platforma za primjenu u raznim područjima, uključujući razvoj senzora, biomaterijala te tkivnog inženjerstva i sustava za dostavu lijekova. Hidro- i organo-gelovi su biokompatibilni, biorazgradivi i netoksični materijali pogodni za primjenu u biomedicini. Kombinacijom supramolekulskih organizacija s različitim anorganskim ili organskim spojevima nastaju nanokompozitni materijali koji imaju poboljšana fizikalna i biološka svojstva. Samoorganizacije organskih molekula male molekulske mase temeljenih na malim peptidima dobro su opisane u literaturi te je pokazana njihova biokompatibilnost. U okviru ovog diplomskog rada, sintetizirani su tripeptidni hidrogelatori Ac-L-Phe-L-Phe-L-Ala-NH2, Ac-L-Phe-L-Phe-L-Ala-OMe i 4-pikolilamidni derivati L-fenilalanin·HCl i D-fenilglicin·HCl. Navedenim gelatorima ispitana su gelirajuća svojstva te je također ispitivano njihovo geliranje dodatkom polimera poli(etilen-glikola) (PEG) i poli(vinil-alkohola) (PVA). Svojstva najboljeg geliranja pokazao je 4-pikolilamidni derivat D-fenilglicina·HCl uz dodatak PVA. Provedeno je preliminarno testiranje kinetike otpuštanja doksorubicina (DOX) iz gela s dodatkom PVA i bez PVA. Rezultati su pokazali da iako PVA utječe na geliranje 4-pikolilamidnog derivata D-fenilglicina·HCl, ubrzava ga i smanjuje kritičnu koncentraciju gelatora, doksorubicin se brže otpušta iz gela koji sadržava PVA.Supramolecular self-organizing functional materials possess specific physical and biological properties that can in some cases be controlled by external stimuli (temperature, pH, UV radiation). They are recognized as an excellent platform for application in various fields, including sensor development, biomaterials, tissue engineering and drug delivery systems. Hydro- and organogels are biocompatible, biodegradable and non-toxic materials that are suitable for biomedical use. Combining supramolecular organizations with various inorganic or organic compounds, nanocomposite materials with improved physical and biological properties are formed. Self-organizations of low molecular weight organic molecules (LMWG) based on small peptides are well described in the literature and their biocompatibility has already been shown. In the framework of this thesis, tripeptide hydrogelators Ac-L-Phe-L-Phe-L-Ala-NH2, Ac-L-Phe-L-Phe-L-Ala-OMe and 4-picolylamide derivatives of L-phenylalanine·HCl and D-phenylglycine·HCl were synthesized. These gels were tested for their gelling properties before and after the addition of polymers of poly (ethylene glycol) (PEG) and poly (vinyl alcohol) (PVA). 4-Picolylamide derivative of D-phenylglycine·HCl with the addition of PVA showed the best gelling properties. Preliminary testing of the release of doxorubicin (DOX) from the gel with the addition of PVA and without PVA has been tested. The results indicate that PVA affects the gelling of 4-picolylamide derivative of D-phenylglycine·HCl, accelerating it and reducing the critical concentration of the gelator while doxorubicin is released more rapidly from the gel containing PVA
Proteini interakcijski partneri TRIOBP-1 i njegov učinak na njihovu agregaciju u shizofreniji
No full textChronic mental illnesses are a group of conditions that include major depressive disorder, bipolar disorder and schizophrenia. These illnesses present with persistent psychiatric symptoms and affect 10.7% of the global population. The emphasis of this thesis is on schizophrenia and disrupted proteostasis as its possible source. This idea stemmed from recent studies that proposed that insoluble, misfolded proteins deposits may not be limited to neurodegenerative disorders, but exist in chronic mental illnesses as well. Several proteins are being investigated for their propensity to aggregate, however, it remains unclear whether these proteins aggregate alone, co-aggregate with each other or recruit other proteins as a part of the pathological processes.
In this thesis we studied the propensity of TRIOBP-1 to aggregate alone and its ability to recruit other proteins to co-aggregate by overexpressing these proteins in neuroblastoma cells. In the first part of research we tested TRIOBP-1 with six of its potential interaction partners, out of which only NDE1 was seen to co-aggregate. Hence, we propose the aggregation mechanism implicating TRIOBP-1 misassembly as responsible for recruiting NDE1 to co-aggregate as well. The second portion of the study focused on researching TRIOBP-1 co-aggregation partners among the proteins previously implicated in chronic mental illness. In these experiments, only DISC1 co-aggregated with TRIOBP-1. Experiments with non-aggregating TRIOBP-1 mutant suggest these proteins are interaction partners as well as co-aggregation partners.
Two out of ten tested proteins were seen to co-aggregate with TRIOBP-1, however, other proteins are not yet to be excluded from their possible involvement in schizophrenia. These newly discovered insoluble deposits could act as a potential biological markers and used for early schizophrenia diagnosis if discovered not to be limited to the brain. They may also provide a valuable insight in underlaying mechanism of non-genetic schizophrenia onset.Kronične mentalne bolesti su skupina poremećaja koji uključuju depresivni poremećaj, bipolarni poremećaj te shizofreniju. Ove bolesti karakteriziraju dugotrajni i razorni psihijatrijski poremećaji te zahvaćaju 10,7% svjetske populacije. Naglasak ovog rada je na shizofreniji i narušenoj proteostazi kao mogućeg izvora bolesti. Ova ideja je proizašla iz nedavnih istraživanja koja predlažu da nakupine netopljivih proteina nisu svojstvene samo neurodegenerativnim poremećajima, već se javljaju i kod kroničnih mentalnih bolesti. Trenutno se ispituje nekoliko proteina koji su pokazali sklonost agregaciji, no zasada ostaje nejasno agregiraju li sami, ko-agregiraju li međusobno ili pak uključuju dodatne proteine u patofiziološke procese.
U ovom radu ispitali smo sposobnost TRIOBP-1 da agregira samostalno i uključuje druge proteine u ko-agregaciju prekomjernom ekspresijom ovih proteina u stanicama neuroblastoma. U prvom dijelu istraživanja testirali smo TRIOBP-1 sa šest njegovih potencijalnih interakcijskih partnera, od kojih je pokazano da jedino NDE1 ko-agregira. Na temelju ovih rezultata predlažemo da je agregacijski mehanizam TRIOBP-1, koji uzrokuje njegovo pogrešno smatanje, odgovoran i za ko-aggregaciju NDE1. Drugi dio istraživanja odnosio se na ispitivanje ko-agregacijskih partnera TRIOBP-1 među proteinima za koje je poznato da su uključeni u kronične mentalne bolesti. U ovom dijelu pokazano je kako samo DISC1 ima sposobnost ko-agregacije s TRIOBP-1. Daljnji eksperimenti s ne-agregirajućim mutantom TRIOBP-1 upućuju na to da su DISC1 i TRIOBP-1 osim ko-aggregacijski partneri, također i interakcijski partneri.
Dva od ukupno deset testiranih proteina ko-agregirali su s TRIOBP-1, ipak, još uvijek se ne može u potpunosti isključiti njihova potencijalna uloga u shizofreniji. Ove neotopive nakupine proteina mogle bi se pokazati kao potencijalni biološki markeri i koristiti za rano otkrivanje shizofrenije ukoliko se pokaže da njihova prisutnost nije ograničena samo na mozak. Ova otkrića mogu pružiti vrijedni novi uvid u temeljne mehanizme nastanka shizofrenije koji nemaju genetski uzrok
Suspected adverse reactions to COVID-19 vaccines reported to the Agency for Medicinal Products and Medical Devices
No full textSARS-CoV-2 virus uzročnik je bolesti COVID-19. SARS-CoV-2 virus se preko proteina šiljka (engl. spike protein) veže na ACE-2 receptore u plućima čovjeka i uzrokuje bolest COVID-19. Infekcija SARS-CoV-2 virusa najčešće dovodi do razvoja težih respiratornih stanja, boli u grlu i suhog kašlja. Apliciranjem cjepiva imunološki sustav čovjeka prepoznaje virusni antigen čime se aktiviraju stanice imunološkog sustava koje stvaraju neutralizirajuća protutijela s ciljem uklanjanja virusnog antigena. Razvijena su cjepiva s ciljem sprječavanja bolesti COVID -19. U Europi najčešće primjenjivana cjepiva jesu mRNK cjepiva (engl. messenger ribonucleic acid; glasnička ribonukleinska kiselina) i adenovirusna cjepiva. U ovome su radu prijave sumnji na nuspojave cjepiva protiv COVID-19 analizirane prema životnoj dobi pacijenta, spolu pacijenta, ozbiljnosti prijave, kriteriju ozbiljnosti, vrsti prijavitelja, prijavljenoj reakciji te pripadnosti nuspojava prema klasifikaciji organskih sustava Medicinskog rječnika za regulatorne poslove (MedDRA). Analizirane prijave ocijenjene su u razdoblju od 27.12.2020. do 1.7.2021. godine. Ukupno je ocijenjeno 2932 prijava sumnji na nuspojave cjepiva protiv bolesti COVID-19, od kojih je njih 730 ocijenjeno ozbiljnima (24,9%). Od 730 ozbiljno ocijenjenih prijava, najveći broj prijava odnosi se na razvoj ostalih medicinski značajnih stanja, njih 583 (70,3%). Najveći broj prijava odnosi se na cjepivo Comirnaty, njih 1610 (54,9%). Zatim slijede prijave sumnji na nuspojave na cjepivo Vaxzevria sa 1098 prijava (27,4%) te Spikevax sa 206 prijava (7,0%). Najmanji broj prijava sumnji na nuspojave odnosi se na cjepivo COVID-19 Vaccine Janssen (15; 0,5%), dok za tri prijave sumnji na nuspojave nije poznato o kojem se cjepivo radi (0,1%).Smrtni ishod prijavljen je u 34 slučaja prijave sumnji na nuspojave, što iznosi tek 4,1% od ukupnog broja ozbiljnih prijava, odnosno 1,15% od ukupnog broja svih zaprimljenih prijava. Najčešće prijavljivane reakcije na cjepiva protiv bolesti COVID-19 bile su vrućica, glavobolja i zimica.The SARS-CoV-2 virus is the cause of COVID-19 disease. The SARS-CoV-2 virus binds to ACE-2 receptors in the human lung via spike protein and causes COVID-19 disease. SARS-CoV-2 virus infection most often leads to the development of severe respiratory conditions, sore throat, and dry cough. By administering the vaccine, the human immune system recognizes the viral antigen, thereby activating immune system cells that produce neutralizing antibodies to remove the viral antigen. To combat the COVID-19 disease pandemic vaccines have been developed. Most commonly used vaccines in Europe are mRNA (messenger ribonucleic acid) vaccines and adenoviral vaccines. In this paper, suspected adverse reactions to the COVID-19 vaccine were analyzed according to patient age, sex, the severity of reporting, severity criteria, type of notifier, reported reaction, and adverse reactions according to the MedDRA classification of organ systems. Analyzed reports of suspected adverse effects were evaluated in the period from 27.12.2020. to 1.7.2021. A total of 2932 reports of suspected adverse reactions to the COVID-19 vaccine were analyzed, of which 730 were considered serious (24.9%). Out of 730 seriously evaluated reports, the largest number of reports refers to the development of other medically significant conditions, 583 of them (70.3%). The largest number of reports relates to the vaccine Comirnaty, 1610 of them (54.9%). This is followed by reports of suspected adverse reactions to Vaxzevria with 1098 reports (27.4%) and Spikevax with 206 reports (7.0%). The lowest number of suspected adverse reactions relates to Vaccine Janssen's COVID-19 vaccine (15; 0.5%), while for three suspected adverse reactions the vaccine is unknown (0.1%). 34 cases of suspected adverse reactions, which amounts to only 4.1% of the total number of serious reports, or 1.15% of the total number of all received reports. The most commonly reported reactions to COVID-19 vaccines were fever, headache, and chills
Porphyrins in photodynamic inactivation of Legionella in biofilm
No full textBakterija Legionella pneumophila često nastanjuje umjetno stvorene sustave voda i izaziva respiratorne bolesti. L. pneumophila u kontaminiranim sustavima stvara biofilm što povećava rezistenciju bakterija na metode dezinfekcije vode koje se najčešće koriste kao što su: termička obrada, kloriranje, dezinfekcija UV zračenjem i ozonom. Fotodinamička inaktivacija jedna je od potencijalnih metoda za dezinfekciju voda, a antimikrobni učinak postiže se kombinacijom netoksičnih komponenti: fotosenzibilizatora, kisika i svjetlosti. U ovome radu korištena su tri kationska porfirinska fotosenzibilizatora, amfifilni spoj TMPyP3-C17H35 i dva hidrofilna spoja TMPyP3-CH3 i TMPyP3. Kao izvor svjetlosti korištena je LED lampa koja emitira ljubičastu svjetlost. Cilj ovoga rada bio je odrediti minimalne efektivne koncentracije spojeva te ispitati anti-adhezijska i anti-biofilm svojstva fotosenzibilizatora u vodama prirodnog podrijetla različite tvrdoće. Sva tri fotosenzibilizatora bila su učinkovita u inhibiciji adhezije L. pneumophila na polistiren i formiranju biofilma u koncentracijama koje odgovaraju MEK vrijednostima od 0,25×MEK i 0,5×MEK u mekoj vodi. U demineraliziranoj vodi zamijećena je najveća toksičnost u mraku i najbolja učinkovitost fotodinamičke inaktivacije pa je moguće da je koncentracija otopljenih iona u vodi, odnosno tvrdoća vode, mogla utjecati na učinkovitost fotodinamičke inaktivacije.The bacterium Legionella pneumophila commonly inhabits artificially made water systems and causes respiratory illnesses. In contaminated systems, L. pneumophila forms biofilm which increases bacterial resistance to most commonly used methods for water disinfection such as thermal processing, chlorination, disinfection by UV radiation and ozone. Photodynamic inactivation is one of the potential methods for water disinfection and its antimicrobial effect is achieved by combining nontoxic components: photosensitizers, oxygen, and light. In this research three cationic porphyrinic photosensitizers were used, amphiphilic compound TMPyP3-C17H35 and two hydrophilic compounds TMPyP3-CH3 and TMPyP3. LED lamp that emits purple light was used as the light source. The focus of this thesis was to determine the minimal effective concentration of photosensitizers and to test the anti-adhesion and anti-biofilm properties of photosensitizers in waters of natural origin and different water hardness. All three photosensitizers were efficient in inhibiting the adhesion of L. pneumophila to polystyrene and against the formation of biofilm in concentrations that correspond to MEK values of 0.25×MEK and 0.5×MEK in soft water. The highest dark toxicity and the best efficiency of photodynamic inactivation were observed in demineralized water which suggests that concentration of dissolved ions in water i.e., water hardness, could have affected the efficiency of photodynamic inactivation
Synthesis of 4,5-dihydrobenzo[b]thieno[2,3-d]oxepine derivatives to test their inhibitory efficiency on NF-kB and JAK/STAT signaling pathways
No full textUpala je obrambeni mehanizam, a istovremeno i jedan od glavnih uzroka mnogih bolesti. Na tržištu se trenutno nalazi niz lijekova s protuupalnim djelovanjem, no s obzirom na gastrointestinalne i kardiovaskularne nuspojave povezane s njihovom primjenom, još uvijek smo u potrazi za novim, djelotvornijim lijekovima. U sklopu ovog diplomskog rada pripravljeni su: etil-8-metoksi-4,5-dihidrobenzo[b]tieno[2,3-d]oksepin-2-karboksilat (5) koji je ključni međuprodukt u sintezi te različiti derivati 4,5-dihidrobenzo[b]tieno[2,3-d]oksepina poput amida 6, alkohola 7 i tri različita aminoalkoksi derivata 8a-c.
Strukture novopripravljenih spojeva razjašnjene su korištenjem spektroskopije 1H i 13C NMR. Spojevima je namjena ispitati protuupalnu učinkovitost, posebice njihovu sposobnost inhibicije NF-κB i JAK/STAT signalnih puteva.Inflammation is a defense mechanism and at the same time common, causative factor in many diseases. There are currently a number of anti-inflammatory drugs on the market, but they are associated with gastrointestinal and cardiovascular side effects. Therefore, we are still pursuing new molecules, which could serve as effective drugs. As part of this thesis, a key intermediate, ethyl-8-methoxy-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-carboxylate (5) as well as various 4,5-dihydrobenzo[b]thieno[2,3-d]oxepine derivatives such as amide 6, alcohol 7 and three different aminoalkoxy derivatives 8a-c were prepared.
The structures of the newly prepared compounds were elucidated on the basis of their 1H and 13C NMR spectra. Anti-inflammatory activity evaluation of the synthesized compounds, especially their ability to inhibit NF-κB and JAK/STAT signaling pathways is planned in the near future
Depresija i antidepresivi
No full textOvaj rad bavi se psihičkom bolešću za koju se smatra da je najrasprostranjenija i sveprisutna među populacijom, a to je depresija.
Depresija je vrlo ozbiljna bolest koju se mora pravovremeno liječiti, a često je neprepoznata ili zanemarena. U radu će biti opisana molekularna priroda depresije, uzroci nastanka te oblici same bolesti, posljedice oboljevanja te antidepresivne terapije. Prikazat će se kompleksnost depresivnog poremećaja i njegov utjecaj na druge tjelesne bolesti. Tema rada zadana je zbog osobnog interesa za područje psihotropnih lijekova i neuropsihijatrije.Within this final thesis depression as a mental illness which is considered to be the most widespread and ubiquitous among the world population, is described. Depression is a very serious disease that must be treatedin a timely manner, and is often unrecognized or neglected. We will reflect on the molecular nature of depression, the causes and consequence of the
disease, and popular choices of antidepressant therapy. The complexity of depressive disorder and its impact on other physical illnesses will be presented. The topic of the final thesis is selected based on personal interest in the field of psychotropic drugs and neuropsychiatry of the candidate