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Pharmacological modalities of cancer pain treatment
No full textKarcinomska bol najsloženiji i najteži je simptom karcinoma i značajno utječe na kvalitetu života pacijenata. Naglasak je na razumijevanju patofiziološke podloge karcinomske boli kao i njezinoj klasifikaciji kako bi se mogla odrediti učinkovita i sigurna farmakoterapija. Za kontrolu karcinomske boli koriste se različite farmakološke skupine lijekova. Paracetamol i nesteroidni protuupalni lijekovi predstavljaju prvi liniju liječenja. Tramadol i tapentadol prethode terapiji opioidima. Opioidi se smatraju zlatnim standardom liječenja karcinomske boli, naglasak je na titraciji doze i sprječavanju pojave nuspojava. Adjuvanti, antidepresivi, antikonvulzivi i kortikosteroidi, koriste se kada opioidi nisu učinkoviti, najčešće kod neuropatske boli ili za pojačavanje analgetskog učinka neopioida i opioida. Ketamin se primjenjuje kod boli koja se ne može kontrolirati drugim terapijskim opcijama. Medicinski kanabinoidi dodatak su drugim propisanim analgeticima, djeluju na neuropatsku komponentnu. Kombinacija lijekova različitog mehanizma djelovanja povećava analgetski učinak svakog pojedinog lijeka, sa smanjenjem učestalosti nuspojava zbog primjene nižih doza lijekova. Uz karcinomsku bol veže se i probijajuća bol koja se kontrolira optimizacijom osnovne analgezije uz primjenu specifične terapije za liječenje probijajuće boli. Cilj liječenja karcinomske boli je očuvati dostojanstvenu kvalitetu života pacijenata do samog kraja.Cancer pain is the most complex and severe symptom of cancer, significantly affecting the quality of life of patients. Emphasis is placed on understanding the pathophysiological basis of cancer pain as well as its classification to enable the determination of effective and safe pharmacotherapy. Various pharmacological groups of drugs are used for the control of cancer pain. Paracetamol and nonsteroidal anti-inflammatory drugs represent the first line of treatment. Tramadol and tapentadol precede opioid therapy. Opioids are considered the gold standard for the treatment of cancer pain, with focus on dose titration and preventing the occurrence of side effects. Adjuvants, antidepressants, anticonvulsants, and corticosteroids are used when opioids are ineffective, most commonly in neuropathic pain or to enhance the analgesic effect of non-opioid and opioid analgesics. Ketamine is used for pain that cannot be controlled by other therapeutic options. Medical cannabinoids are an addition to other prescribed analgesics and act on the neuropathic component. The combination of drugs with different mechanisms of action increases the analgesic effect of each individual drug while reducing the frequency of side effects by applying lower doses of each medication. Along with cancer pain, breakthrough pain is often present and is controlled by optimizing the basic analgesia, with the application of specific therapies for treating breakthrough pain. The goal of cancer pain treatment is to preserve the dignified quality of life of patients until the end
In vitro antimicrobial and anti-inflammatory activity of Erodium cicutarium (L.) L'Her. ex Aiton
No full textU okviru doktorskog rada provedena su ispitivanja antimikrobnog, protuupalnog te antioksidacijskog djelovanja ekstrakata
vrste Erodium cicutarium (L.) L’Hér. ex Aiton, Geraniaceae u uvjetima in vitro. Ispitivanja navedenih aktivnosti praćena su
opsežnom fitokemijskom analizom ektrakata i eteričnog ulja. Antimikrobna aktivnost iscrpina poglavito je izražena na
sojeve vrste Staphylococcus aureus, uključujući i kliničke MRSA sojeve. Uz pokazanu kinetiku bakteriostatskog i
baktericidnog učinka u vremenu te anti-biofilm aktivnost, bioautografijom je uz semipreparativnu izolaciju i UHPLC-LTQ
OrbiTrap MS4 analizu, kao vrhunac ovog doktorskog rada, provedena izolacija i karakterizacija antimikrobno aktivnih
frakcija. Dobiveni rezultati ukazuju na derivate galne kiseline kao spojeve poglavito odgovorne za opaženi antimikrobni
učinak. Među njima je najzastupljeniji spoj galoil šikiminska kiselina. Poseban je naglasak i na 7 spojeva iz antimikrobno
aktivnih frakcija, koji su po prvi puta unutar ovog doktorskog rada identificirani za vrstu E. cicutarium, rod Erodium, te
porodicu Geraniaceae. To su narcisin, galoil pentozid izomer 1 i izomer 2, metilgaloil-kafeoil heksozid, metilgaloil-kumaroil
heksozid, te izomer 1 i izomer 2 trimetilelagične kiseline. Protuupalni potencijal vrste E. cicutarium u uvjetima in vitro
ponajprije je pokazan kroz rezultate izravne inhibicije enzima COX1 i COX2 i inhibiciju citokina IL-6, te inhibiciju lučenja
dušik (II) oksida na modelu THP-1 stanica. Antioksidacijsku aktivnost u uvjetima in vitro, ispitanu metodama DPPH, ABTS,
FRAP, CUPRAC te metodom izbjeljivanja β-karotena, pokazali su svi ispitani uzorci u svim provedenim pokusnim
uvjetima. Detaljan polifenolni profil vrste E. cicutarium utvrđen je metodom UHPLC-LTQ OrbiTrap MS4. Analizirane su
metanolne i vodene iscrpine ove vrste s četiri lokaliteta na području Republike Hrvatske (Podvinje, Plitvice, Trešnjevka,
Buzin), a identificirano je ukupno 85 sastavnica. Najzastupljeniji su derivati galne kiseline (24 sastavnice), derivati elagične
kiseline – uključujući elagitanine (22 sastavnice), 19 flavonolnih glikozida, 8 derivata fenolnih kiselina, 7 derivata drugih
hidroksibenzojevih kiselina, 3 flavonolna aglikona te 2 procijanidina. Nagasak je na 25 identificiranih sastavnica, koje do
sada nisu pronađene unutar roda Erodium, te porodice Geraniaceae. Od ukupno 17 kvantificiranih sastavnica metodom
UHPLC-QqQ-MS/MS provedena je kvantifikacija sastavnica, među kojima je najzastupljenija galna kiselina. GC-MS
analizom eteričnog ulja ukupno je identificirano 50 spojeva, s ugljikovodicima kao glavnom skupinom spojeva
(najzastupljeniji spoj je heksadekanoična kiselina).Research in this doctoral thesis was focused on in vitro antimicrobial, ani-infammatory, and antioxidative activity of
Erodium cicutarium (L.) L’Hér. ex Aiton, Geraniaceae extracts, strongly underlined with phytochemical characterization of
extracts and the essential oil. Antimicrobial activity was evident, especially against Staphylococcus aureus strains, including
MRSA. Next to observed anti-biofilm activity, the time-kill assay was performed and bactericidal and bacteriostatic activity
were studied in time. As a highlight of this work, active antimicrobial fractions were identified, isolated and extensively
phytochemically characterized using UHPLC-LTQ OrbiTrap MS4. Obtained results indicate that gallic acid derivatives
could be the compounds most responsible for the observed in vitro antimicrobial activity. Galloyl-shikimic acid was
identified as the most abundant compound among them. To stress out, 7 of the identified compounds are compounds
detected for the first time not only for E. cicutarium, but in the Geraniaceae family as well. Among them narcissin, galloyl
pentoside isomer 1 and isomer 2, methylgalloyl-caffeoyl hexoside, methylgalloyl-coumaroyl hexoside, trimethylellagic acid
isomer 1 and isomer 2. In vitro anti-inflammatory activity testing of E. cicutarium extracts showed inhibitory activity on
COX-1 and COX-2, cytokine IL-6 production, as well as on production of NO, indicating their anti-inflammatory activity.
TNF-α production was induced, showing the potential of E. cicutarium extracts for immunomodulation. In vitro antioxidant
activity was shown for all samples in all performed assays – DPPH, ABTS, FRAP, CUPRAC and the β-carotene bleaching
assay. Detailed phenolic profiling of water and methanol extracts was undertaken with UHPLC-LTQ OrbiTrap MS4 for
identification, and UHPLC-QqQ-MS/MS for quantification. Samples were collected from 4 localities in Croatia (Podvinje,
Plitvice, Trešnjevka, Buzin). In total, 85 phenolic compounds were identified. Among them mainly gallic acid derivatives
(24 compounds), ellagic acid derivatives, including ellagitannins (22 compounds), 19 flavonol glycosides, 8
hydroxycinnamic acid derivatives, 7 other hydroxybenzoic acid derivatives, 3 flavonol aglycones, and 2 procyanidins. Very
important results from this study show the presence of newly identified compounds – 25 new compounds were found, that
have not been reported for the Erodium genera or the Geraniaceae family before. Among 17 quantified components, gallic
acid stands out as the phenolic constituent with highest quantified content among all samples. The GC-MS analysis of
essential oils showed a total of 50 identified compounds. Hydrocarbons are the main class of constituents, with hexadecanoic acid as the major component
Kemijska sudbina zabrinjavajućih farmaceutika u okolišu: eksperimentalno i računalno istraživanje produkata razgradnje i njihovih ekotoksikoloških svojstava
No full textPregledom literature uočeno je da eksperimentalni (i računalni) podaci o kemijskoj sudbini lijekova (kandidata za Četvrti popis praćenja) nedostaju ili su nepotpuni. Tako, na primjer, u studijama o fotokemijskoj razgradnji karbamazepina ili ciklofosfamida strukture produkata nisu izolirane/dokazane (Ghoul 2019, Lutterbeck 2015), dok u nedavnom istraživanju kloriranja gabapentina nisu opisana ekotoksikološka svojstva nastalih oksidacijskih produkata (Ra 2020). Takvi će slučajevi, stoga, biti na listi naših prioriteta, odnosno odabranih kandidata za čiju kemijsku sudbinu nedostaju potpune informacije o reakcijama induciranim kloriranjem i/ili zračenjem, o ekotoksikološkim svojstvima (eventualnih) nusprodukata ili o fizikalno-kemijskim parametrima struktura izračunatih kvantno-kemijskim metodama. U ovom se projektu izbor zabrinjavajućih farmaceutika temelji na službenim prioritetima i kategorijama uvedenim od strane Europske komisije kroz Popis za praćenje tvari u sklopu Okvirne direktive o vodama (2000/60/EC). Kemijske promjene mnogih farmaceutika u uvjetima kloriranja ili zračenja, redoviti postupci kojima su podvrgnute ili izložene okolišne vode, nije poznata, kao ni ekotoksikološki učinak nastalih produkata. Praznine u razumijevanju kemijske sudbine relevantnih farmaceutika područje su istraživanja predloženog projekta, a u realizaciji tog cilja sudjelovat će stručnjaci s potrebnom ekspertizom i s pristupom širokom spektru eksperimentalnih i računskih alat
Evaluation of the membrane elasticity of various vesicular phospholipid gels containing ciprofloxacin or thymol
No full textSvrha ovog rada bila je odrediti membransku elastičnost vezikularnih fosfolipidnih gelova (VFG-ova) s ciprofloksacinom i timolom različitog (fosfo)lipidnog sastava. Formulacije VFG-ova pripravljene su metodom visokotlačne homogenizacije te su se međusobno razlikovale (fosfo)lipidnim sastavom, prisustvom suotapala (propilenglikol), rubnog aktivatora (monoacil fosfatidilkolin) i polimera (kitozan). Ispitivan je utjecaj sastavnica VFG-a na fluidnost (elastičnost/rigidnost) njegovih dvoslojeva. Najelastičnije dvoslojeve imali su VFG-ovi s ciprofloksacinom koji su uz osnovni fosfolipid (SPC) sadržavali rubni aktivator (monoacil fosfatidilkolin) i propilenglikol, potom VFG-ovi s propilenglikolom te oni koji su uz SPC sadržavali monoacil fosfatidilkolin. Nasuprot tome, prisutnost kolesterola, kitozana i hidrogeniranih fosfolipida rezultirala je porastom rigidnosti membrana VFG-ova, pri čemu su VFG-ovi s hidrogeniranim fosfolipidima bili karakterizirani najčvršćim dvoslojevima (najmanji stupanj elastičnosti). Osim sastavnica VFG-a, dokazano je i da lipofilnost uklopljenog lijeka utječe na stupanj membranske elastičnosti. Pritom su membrane VFG-ova s timolom bile nešto elastičnije od dvoslojeva VFG-ova s ciprofloksacinom istog (fosfo)lipidnog sastava.The purpose of this study was to determine membrane elasticity of vesicular phospholipid gels (VPGs) containing ciprofloxacin or thymol. VPGs, differing in (phospho)lipid composition, with or without addition of a co-solvent (propylene glycol), an edge activator (monoacyl phosphatidylcholine) and a polymer (chitosan), were prepared using high-pressure homogenization method. The influence of the VPGs' ingredients on the fluidity (elasticity/rigidity) of their bilayers was examined. Ciprofloxacin-VFGs, which in addition to the basic phospholipid (SPC) contained an edge activator (monoacyl phosphatidylcholine) and propylene glycol, were characterized by the most elastic bilayers, followed by VPGs containing propylene glycol and those containing SPC and monoacyl phosphatidylcholine. On the other hand, the presence of cholesterol, chitosan, and hydrogenated phospholipids resulted with increase in the membrane rigidity, where VPG containing hydrogenated phospholipids exhibited the most rigid bilayers. In addition to VPG ingredients, the lipophilicity of the incorporated drug was also shown to influence the degree of membrane elasticity. In this regard, VPGs with thymol were slightly more elastic than those with ciprofloxacin of the same (phospho)lipid composition
The influence of patients' attitudes and beliefs about medicines on the adherence in women with advanced breast cancer
No full textRak dojke najraširenija je zloćudna bolest na svijetu. Svaka četvrta žena s karcinomom ima rak dojke. Vjerojatnost razvitka metastaza iz primarnog tumora je 23-30%. Cilj je terapije uznapredovalog raka dojke usporiti ili potpuno prevenirati progresiju bolesti uz olakšanje simptoma i nuspojava liječenja. Pojavom djelotvornih oralnih antitumorskih lijekova, adherencija na terapiju postala je jedan od temeljnih uvjeta za uspješnost ishoda liječenja. Cilj ovog rada bio je ustanoviti adherenciju bolesnica s uznapredovalim rakom dojke na oralne antitumorske lijekove te istražiti socio-demografske i kliničke čimbenike koji utječu na adherenciju. S obzirom na to da je dokazano kako adherencija također ovisi o osobnoj percepciji bolesnika prema lijekovima i bolesti, dodatno su istraženi stavovi i uvjerenja bolesnika o lijekovima te njihova povezanost s adherencijom. Provedeno je presječno, opservacijsko istraživanje u koje su bile uključene žene s metastatskim rakom dojke (stadij IV), a koje primaju oralnu antitumorsku terapiju. Adherencija je mjerena pomoću Upitnika za procjenu adherencije (MARS-5), a stavovi i uvjerenja bolesnika pomoću BMQ upitnika (engl. Beliefs about Medicines Questionnaire). Sudjelovalo je 89 žena starijih od 18 godina, medijana dobi 60 godina (interkvartilni raspon 47-70). Bolesnice su pokazale iznimno visok stupanj adherencije na terapiju oralnim antitumorski lijekovima, srednja vrijednost bodova na MARS-5 skali iznosila je 24,16 ± 1,563 od mogućih 25 bodova. Utvrđena je statistički značajna povezanost maksimalne adherencije s terapijom inhibitorima CDK4/6 (p=0,018). Žene koje su na terapiji inhibitorima CDK4/6 pokazale su viši stupanj adherencije u odnosu na one koje su bile na drugoj oralnoj antitumorskoj terapiji. Općeniti i specifični stavovi i uvjerenja bolesnica o njihovim lijekovima pokazali su se izrazito pozitivnima. Također je uočena povezanost s adherencijom na tri skale BMQ upitnika: Opći dio – Prekomjerna uporaba lijekova, Opći dio – Osjetljivost na lijekove te Specifični dio – Zabrinutost zbog lijekova (p=0,024; p=0,043; p=0,036). Ovim su istraživanjem ustanovljeni neki od čimbenika koji utječu na adherenciju bolesnica s uznapredovalim rakom dojke te smo time pridonijeli razumijevanju adherencije u populaciji koja dosad nije bila istraživana u Hrvatskoj. Prvi su puta proučeni stavovi i uvjerenja navedenih bolesnica o lijekovima te povezani s adherencijom. Bolje razumijevanje istraživanih čimbenika i uzroka potencijalne neadherencije može poslužiti u razvoju intervencija za povećanje adherencije.Breast cancer is the most widespread malignant disease in the world. Every fourth woman with cancer has breast cancer. The probability of developing metastases from the primary tumor is 23-30%. The goal of advanced breast cancer therapy is to slow down or completely prevent the progression of the disease while relieving the symptoms and side effects of the treatment. With the invention of effective oral antitumor drugs, adherence to therapy has become one of the fundamental conditions for successful treatment outcomes. The aim of this work was to establish the adherence of patients with advanced breast cancer to oral antitumor drugs and to investigate socio-demographic and clinical factors that influence adherence. Given that it has been proven that adherence also depends on the patient's personal perception of medication and disease, the patient's attitudes and beliefs about medicine and their association with adherence were additionally investigated. A cross-sectional, observational study was conducted in which women with advanced breast cancer (stage IV) and receiving oral antitumor therapy were included. Adherence was measured using The Medication Adherence Report Scale (MARS-5), and patients' attitudes and beliefs were measured using the Beliefs about Medicines Questionnaire (BMQ). 89 women over the age of 18 participated, median age 60 (IQR 47-70). The patients showed a very high degree of adherence to oral antitumor therapy, the mean value of the MARS-5 questionnaire was 24,16 ± 1,563 out of a possible 25 points. A statistically significant association between adherence and CDK4/6 inhibitors was observed (p=0.018). Women taking CDK4/6 inhibitors therapy showed a higher degree of adherence compared to those who were taking other oral antitumor therapy. The general and specific attitudes and beliefs about medicines turned out to be very positive. The association was also found between adherence and three BMQ scales: General - Overuse, General – Perceived Sensitivity to Medicines and Specific - Concerns (p=0.024; p=0.043; p=0.036). This research established some of the factors that influence the adherence of patients with advanced breast cancer, and thus we contributed to the understanding of adherence in a population that had not been studied in Croatia before. For the first time, the attitudes and beliefs of the above-mentioned patients about medication were studied and related to adherence. A better understanding of the researched factors and causes of potential non-adherence can help in the development of interventions to increase adherence
Electroanalytical methods for the determination of statins
No full textStatini su prva linija liječenja hiperlipidemije, bolesti od koje boluje čak 39% svjetske populacije.
Stoga je od iznimne važnosti razvijati osjetljive i precizne analitičke metode za njihovo
određivanje u različitim uzorcima. Elektroanalitičke metode nametnule su se zbog svoje brzine
analize, jednostavnosti izvedbe te financijske i ekološki prihvatljivosti.
U ovom diplomskom radu napravljen je pregled voltametrijskih metoda razvijenih u svrhu
određivanja statina ili simultanog određivanja različitih lijekova uz statine u farmaceuskim
oblicima i različitim biološkim uzorcima. Pritom su u ispitivanju najčešće korištene diferencijalno
pulsna i pravokutnovalnavoltametrija, no osim njih primjenjivane su i linearna sweep, stripping i
ciklička voltametrija. Korišteno je više vrsta elektroda: elektroda od ugljikove paste, elektroda od
grafitne mine, dijamantna elektroda obogaćena borom, elektroda s visećom živinom kapi i screen
printed elektroda, od kojih je u najvećem broju analiza bila primjenjivana elektroda od staklastog
ugljika. Elektrode su nerijetko bile modificirane različitim postupcima i materijalima u svrhu
povećanja osjetljivosti metode te poboljšanja prijenosa elektrona na površini senzora. Najčešće su
u modifikaciji bili primjenjivani nanomaterijali, od kojih u najvećem broju slučajeva ugljikove
nanocijevi i nanočestice različitih metala.Statins are the first line of treatment for hyperlipidemia, a disease that affects as much as 39% of
the world's population. Therefore, it is of utmost importance to develop sensitive and precise
analytical methods for their determination in different samples. Electroanalytical methods have
become popular due to their speed of analysis, ease of implementation, and financial and
environmental acceptability.
This thesis reviews voltammetric methods developed for the determination of statins or
simultaneous determination of different drugs with statins in pharmaceutical forms and different
biological samples. Differential pulse and squarewave voltammetry were most commonly used for
determination, however linear sweep, stripping, and cyclic voltammetry were also applied. Several
types of electrodes were used: carbon paste electrode, pencil graphite electrode, boron-doped
diamond electrode, hanging mercury drop electrode and screen printed electrode, of which glassy
carbon electrode was used in the majority of analyses. Electrodes have often been modified with
various methods and materials to increase the sensitivity of the method and improve electron
transfer on the sensor surface. The most common modification used was nanomaterials, most often
carbon nanotubes and nanoparticles of various metals
Development of a high-throughput method for the N-glycosylation analysis of fibrinogen
No full textGlikozilacija je jedna od najvažnijih posttranslacijskih modifikacija koja značajno utječe na biološke funkcije i strukturu proteina. Fibrinogen, ključni protein u procesu zgrušavanja krvi, podliježe N-glikozilaciji na glikozilacijskim mjestima Asn394 na β-lancu i Asn78 na γ-lancu. Analiza N-glikozilacije fibrinogena mogla bi pružiti uvid u potencijalne glikozilacijske promjene ovog proteina u različitim patološkim stanjima poput KOPB-a i kardiovaskularnih bolesti. Cilj ovog istraživanja bio je stoga razviti visokoprotočnu metodu za analizu N-glikozilacije fibrinogena iz uzorka krvne plazme. Obogaćivanje fibrinogena provedeno je precipitacijom etanolom, a glikozilacija je analizirana na razini glikopeptida.
Ispitano je šest različitih eksperimentalnih uvjeta za pripremu i analizu glikopeptida fibrinogena. Za svaki uvjet, MS1 analizom uspoređeni su apsolutni signali glikopeptida, pri čemu je eksperimentalni uvjet s 16% etanola u odnosu na volumen plazme pokazao najvišu osjetljivost i reproducibilnost analize. Za potvrdu glikoformi korištena je MS/MS analiza, pri čemu je fragmentacija najdominantnije glikoforme (A2G2S1) na oba glikozilacijska mjesta pokazala očuvanje peptidne sekvence uz karakterističan raspad glikanske strukture. Na temelju poznatih podataka iz literature o glikanskim strukturama fibrinogena te retencijskih vremena njihovih glikopeptida, identificirane su i potvrđene dvije najzastupljenije glikoforme (A2G2S1 i A2G2S2) na oba glikozilacijska mjesta, kao i dodatne glikoforme: A2G2, FA2G2S1 i FA2G2S2 na β-lancu te FA2G2S1 i FA2G2S2 na γ-lancu.
Ovo istraživanje uspješno je razvilo visokoprotočnu metodu za N-glikoprofiliranje fibrinogena iz krvne plazme te omogućilo detaljno određivanje njegovih glikanskih struktura i glikozilacijskog mjesta s kojeg potječu. Dobiveni rezultati pružaju temelj za daljnja istraživanja u području glikoproteomike te potencijalnu primjenu u identifikaciji biomarkera i proučavanju uloge glikozilacije fibrinogena u različitim bolestima.Glycosylation is one of the most important post-translational modifications that significantly affects the biological functions and structure of proteins. Fibrinogen, a key protein in the blood coagulation process, undergoes N-glycosylation at glycosylation sites Asn394 on the β-chain and Asn78 on the γ-chain. Analyzing fibrinogen N-glycosylation could provide insight into potential glycosylation changes in various pathological conditions such as COPD and cardiovascular diseases. The aim of this research was to develop a high-throughput method for analyzing fibrinogen N-glycosylation from a blood plasma sample. Fibrinogen enrichment was performed by ethanol precipitation, and glycosylation was analyzed at the glycopeptide level.
Six different experimental conditions for fibrinogen glycopeptide preparation and analysis were tested. For each condition, absolute glycopeptide signals were compared by MS1 analysis, with the experimental condition with 16% ethanol relative to plasma volume showing the highest sensitivity and reproducibility of the analysis. MS/MS analysis was used to confirm the glycoforms, with the fragmentation of the most dominant glycoform (A2G2S1) at both glycosylation sites showing peptide sequence preservation along with the characteristic fragmentation of the glycan structure. Based on known literature data on fibrinogen glycan structures and the retention times of their glycopeptides, two most abundant glycoforms (A2G2S1 and A2G2S2) were identified and confirmed at both glycosylation sites, as well as additional glycoforms: A2G2, FA2G2S1 and FA2G2S2 on the β-chain, and FA2G2S1 and FA2G2S2 on the γ-chain.
This study successfully developed a high-throughput method for N-glycoprofiling of fibrinogen from blood plasma, enabling detailed characterization of its glycan structures and their glycosylation sites of origin. The obtained results provide a foundation for further research in the field of glycoproteomics and potential application in biomarker identification and studying the role of fibrinogen glycosylation in various diseases
The impact of bisphenol A on the antioxidant and antidiabetic properties of common onion (Allium cepa L.)
No full textBisfenol A (BPA) koristi se kao sirovina u proizvodnji epoksidnih smola i plastike. Proizvodnja i odlaganja takvih proizvoda u okolišu dovelo je do sve veće prisutnost BPA u okolišu. Pokazano je da BPA negativno utječe na zdravlje ljudi tako što djeluje kao endokrini disruptor te uzrokuje oksidacijski stres. Cilj ovog istraživanja bio je ispitati učinak BPA na antioksidacijsku i antidijabetsku aktivnost u lukovica običnog luka (Allium cepa L.). Pokus je proveden tako da su 5 skupina po 10 lukovica luka bile izložene otopinama BPA u rasponu koncentracija od 1 do 50 mg/L tijekom tri dana. Jedna je skupina lukovica (n=10) bila izložena destiliranoj vodi te je služila kao kontrola. Antioksidacijska aktivnost lukovica luka ispitana je FRAP, DPPH i ABTS metodama, a antidijabetska aktivnost ispitana je metodom BSA glikacije. Rezultati istraživanja pokazali su da trodnevna izloženost BPA dovodi do pad redukcije željezovih iona i inhibicije slobodnih radikala u usporedbi s kontrolom što ukazuje na to da BPA smanjuje antioksidacijsku aktivnost biljke. Također, u usporedbi s kontrolom trodnevna izloženost najvišoj koncentraciji BPA smanjila je sposobnost inhibicije glikacije proteina biljke. Ovo istraživanje potvrđuje štetno djelovanje BPA na biljke tako što dovodi do smanjenja njihove antioksidacijske i antidijabetske aktivnosti te ukazuje na važnost kontrole količine BPA u okolišu kako bi se smanjili njegovi štetni učinci na okoliš i zdravlje ljudi.Bisphenol A (BPA) is used as a raw material in the production of epoxy resins and plastics. Production and release of such products in the environment has led to increased presence of BPA in the environment. It is demonstrated that BPA has negative effects on human health by acting as an endocrine disruptor and causing oxidative stress. The aim of this study was to investigate the impact of BPA on antioxidant and antidiabetic activities of onion bulbs (Allium cepa L.). In the experiment five groups (each consisting of 10 bulbs) were exposed to BPA at concentrations from 1 to 50 mg/L for three days. One group of onions (n=10 bulbs) was exposed to distilled water and served as control. Following exposure, in onion bulbs antioxidant activity was evaluated using the FRAP, DPPH, and ABTS methods, while antidiabetic activity was assessed using the BSA glycation method. The results of this investigation showed that three-day exposure to BPA caused a decrease in iron ion reduction and free radical inhibition in comparison to the control, indicating that BPA decreases the antioxidant activity of the plants. Also, in comparison to the control three-day exposure to the highest BPA concentration reduced the plants’ ability to inhibit protein glycation. This study confirms the harmful effects of BPA on plants by reducing their antioxidative and antidiabetic activity and underscores the importance of regulating the amount of BPA released into the environment to minimize its adverse effects on the environment and human health
Overcoming barriers in formulating practically insoluble loteprednol etabonate in ophthalmic nanoemulsion
No full textLoteprednol etabonate (LE) is a soft corticosteroid recently approved for the short-term treatment of signs and symptoms of dry eye disease. LE is available on the market as a suspension, which can release only limited amount of dissolved corticosteroid after application at the ocular surface. This study is focused on the development of an oil-in-water nanoemulsion (NE) to effectively deliver dissolved LE to the ocular surface, in order to promote its absorption. We newly developed an extended-throughput 3D model of the corneal epithelium for biocompatibility study, and an innovative approach to investigate the effect of biorelevant dilution on LE release from the NE oil phase. Castor oil, Capryol® 90, Kolliphor® EL and Soluplus® were selected as NE excipients based on their potential to dissolve LE. Design of experiments was successfully employed to develop biocompatible and physically stable NE with high LE content (0.15 %, w/w) and retention efficiency (87 % after 10 months of storage at room temperature). LE retention within oil droplets (above 90 % of the initial LE content) despite biorelevant dilution simulating tear turnover suggests the potential for direct LE absorption from the NE oil droplets into the lipophilic corneal epithelium. The results obtained encourage the extension of the studies in terms of in vitro permeability and in vivo eye-related bioavailability assessment to prove the potential of the proposed LE formulation
Adherencija pacijenta u liječenju antidepresivima
No full textCilj istraživanja: Cilj specijalističkog rada je pregledno prikazati probleme adherencije kod pacijenata na antidepresivima, sistematizirati identificirane uzroke neadherencije, a zatim pregledno prikazati postojeće alate koji se koriste u promoviranju adherentnog ponašanja. Jedan od ciljeva je i smjestiti ulogu ljekarnika i ljekarničkih intervencija u optimizaciji adherencije i potencijalnom olakšavanju simptoma bolesti.
Materijali i metode: U svrhu izrade i oblikovanja ovog rada proučena je stručna i znanstvena literatura pronađena pretraživanjem bibliografskih baza podataka: PubMed, ScienceDirect i Google Scholar uz primjenu ključnih riječi povezanih s temom istraživanja. Literatura je pretražena od općih prema specijaliziranim člancima pri čemu su izdvojeni članci relevantni za traženu problematiku, a najvažniji rezultati, rasprave i zaključci prikazani su u ovom specijalističkom radu.
Rezultati: Iako bi pacijenti trebali primijeniti svu propisanu količinu lijeka, stope adherencije kod bolesnika s depresivnim poremećajem na terapiji antidepresivima variraju od 10 do 60 %. Čimbenici utjecaja na adherenciju pregledani u ovom radu su dob i spol bolesnika, njihov socio-ekonomski status, etnička pripadnost, čimbenici vezani za samog bolesnika i bolest, stigma kao dodatni teret depresije, čimbenici vezani za terapiju, čimbenici odnosa bolesnika i zdravstvenog radnika i čimbenici vezani za zdravstveni sustav. Također je pregledan utjecaj ljekarničkih intervencija na poboljšanje adherencije.
Zaključak: U svrhu optimizacije adherencije kod pacijenata liječenih antidepresivima nužno je povećati zdravstvenu pismenosti pacijenta tj. njihovo razumijevanje vlastite bolesti i terapije, za čime slijedi ostvarenje zdravog odnosa povjerenja između pacijenta i propisivača, prilagodba terapije individualnim potrebama pacijenta te olakšan pristup i veća dostupnost zdravstvenog sustava. Poboljšanje adherencija zahtijeva multidisciplinarni pristup liječnika specijalista psihijatrije i obiteljske medicine, psihologa, socijalnih radnika, medicinskih sestara i ljekarnika. Istraživanja ukazuju da ljekarničke intervencije povećavaju stopu adherencije, no pitanje olakšavaju li ujedno i simptome bolesti ostaje otvoreno za daljnja istraživanja.Objectives: The aim of the thesis is to present the problems of adherence in patients on antidepressant therapy, systematize identified causes of non-adherence, and then review existing tools used to promote adherent behavior. One of the aims is to place the role of pharmacists and pharmacist interventions in optimizing adherence and potentially alleviating disease symptoms.
Materials and methods: For the purpose of creating this thesis, professional and scientific literature was studied by searching bibliographic databases: PubMed, ScienceDirect and Google Scholar with the use of keywords related to the research topic. The literature was searched from general to specific articles, after which articles relevant to the issues were selected, with the most important results, discussions and conclusions presented in this review.
Results: Patients should administer the entire prescribed amount of medication, but adherence rates in patients with depressive disorders on antidepressant therapy vary from 10 to 60 %. Factors influencing patient adherence reviewed in this thesis include age and gender of the patient, their socio-economic status, ethnicity, stigma as an additional burden of depression, factors related to the patient and the disease itself, factors related to pharmacotherapy, factors related to the patient's relationship with their healthcare provider and factors related to the healthcare system. The impact of pharmacist interventions on improving adherence rate was also reviewed.
Conclusion: In order to optimize adherence in patients treated with antidepressants, it is necessary to increase patient's health literacy, i.e. their understanding of their own illness and therapy, then establish a healthy and trustworthy patient-prescriber relationship, adapt pharmacotherapy to patient's individual needs and achieve easier access to the healthcare system. Improving adherence requires a multidisciplinary approach that involves psychiatry specialists, family medicine, psychologists, social workers, nurses and pharmacists. Research indicates that pharmacist interventions increase adherence rate, but the question of whether they also alleviate the symptoms of the disease remains open for further research